nm23 regulates decidualization through the PI3K-Akt-mTOR signaling pathways in mice and humans.

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Zhang, Xue; Fu, Li-Juan; Liu, Xue-Qing; Hu, Zhuo-Ying; Jiang, Yu; Gao, Ru-Fei; Feng, Qian; Lan, Xi; Geng, Yan-Qing; Chen, Xue-Mei; He, Jun-Lin; Wang, Ying-Xiong; Ding, Yu-Bin

2016-10-01

Does nm23 have functional significance in decidualization in mice and humans? nm23 affects decidualization via the phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathways in mouse endometrial stromal cells (ESCs; mESCs) and human ESCs. The function of nm23 in suppressing metastasis has been demonstrated in a variety of cancer types. nm23 also participates in the control of DNA replication and cell proliferation and differentiation. We first analyzed the expression profile of nm23 in mice during early pregnancy (n = 6/group), pseudopregnancy (n = 6/group) and artificial decidualization (n = 6/group) and in humans during the menstrual cycle phases and the first trimester. We then used primary cultured mESCs and a human ESC line, T-HESC, to explore the hormonal regulation of nm23 and the roles of nm23 in in vitro decidualization, and as a possible mediator of downstream PI3K-Akt-mTOR signaling pathways. We evaluated the dynamic expression of nm23 in mice and humans using immunohistochemistry, western blot and real-time quantitative RT-PCR (RT-qPCR). Regulation of nm23 by steroid hormones was investigated in isolated primary mESCs and T-HESCs by western blot. The effect of nm23 knockdown (using siRNA) on ESC proliferation was analyzed by 5-ethynyl-2'-deoxyuridine staining (EdU) and proliferating cell nuclear antigen protein (PCNA) expression. The influence of nm23 expression on the differentiation of ESCs was determined by RT-qPCR using the mouse differentiation markers decidual/trophoblast PRL-related protein (dtprp, also named prl8a2) and prolactin family 3 subfamily c member 1 (prl3c1) and the human differentiation markers insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL). The effects of nm23 siRNA (si-nm23) and the PI3K inhibitor LY294002 on the downstream effects of nm23 on the PI3K-Akt-mTOR signaling pathway were estimated by western blot. NM23-M1 was specifically expressed in the decidual zone

[Observation of osteoclasts on the root surface during human deciduous teeth resorption].

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Bao, Xiang-jun; Liang, Xing; Chen, Ming; Wang, Hang; Xie, Zhi-gang; Yang, Xiao-yu

2004-08-01

To observe osteoclasts on the resorbing surface of human deciduous teeth. After fixing the collected deciduous teeth, we prepared the tooth slices without decalcification, treated them with HE and TRAP dyestuff, and observed the osteoclasts under light and scanning electron microscope. There were large quantity of various forms of overlapping and huge osteoclasts with many nuclei and silk-like protuberances on the resorbing surface of deciduous teeth. The multinucleated osteoclasts align on the surface of coarse dentin. On the resorbing surface of human deciduous teeth there are large amount of osteoclasts which can be used as a source of studying human osteoclast.

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...

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...

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....

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.

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.

Cyclin G1 inhibits the proliferation of mouse endometrial stromal cell in decidualization

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Xu Qian

2017-01-01

Full Text Available Uterine stromal cell decidualization is a dynamic physiological process in which cell proliferation, differentiation and apoptosis are orchestrated and occur in a temporal and cell-specific manner. This process is important for successful embryo implantation. Many cell-cycle regulators are involved in decidualization. The protein cyclin G1 is a unique regulator of the cell cycle with dual functions in cell proliferation. It was reported that cyclin G1 is expressed in mouse uterine stromal cells during the period of peri-implantation. To prove the function of cyclin G1 in mouse uterine stromal cells during this period, immunohistochemistry was used to stain mouse uterine tissues on days 4-8 of pregnancy. The results showed obvious spatial and temporal expression of cyclin G1 in uterine stromal cells, and that it is expressed in the cells of the primary decidual zone (PDZ on day 5 and secondary decidual zone (SDZ on days 6 and 7, when the stromal cells experienced active proliferation and differentiation was initiated. Applying the decidualization model of cultured primary stromal cells in vitro, we further revealed that the expression of cyclin G1 is associated with decidualization of stromal cells induced by medroxyprogesterone acetate (MPA and estradiol-17β (E2. RNA interference was used for the knockdown of cyclin G1 in the induced decidual cells. Flow cytometry analysis indicated that the proportion of cells in the S stage was increased, and decreased in the G2/M phase. Our study indicates that cyclin G1, as a negative regulator of the cell cycle, plays an important role in the process of decidualization in mouse uterine stromal cells by inhibiting cell-cycle progression.

Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner.

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Leno-Durán, E; Ruiz-Magaña, M J; Muñoz-Fernández, R; Requena, F; Olivares, E G; Ruiz-Ruiz, C

2014-10-10

Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua

Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization.

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Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

2015-01-01

Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polyploidization of decidual cells. E2F8-mediated polyploidization is a response to stresses which are accompanied by decidualization. Interestingly, polyploidization is not detected during human decidualization with the down-regulation of E2F8, indicating differential expression of E2F8 may lead to the difference of decidual cell polyploidization between mice and humans.

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.

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

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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.

Bone marrow origin of decidual cell precursors in the pseudopregnant mouse uterus

International Nuclear Information System (INIS)

Kearns, M.; Lala, P.K.

1982-01-01

Decidual cells are considered to be the endproduct of a hormonally induced transformation of endometrial stromal cells of the uterus. However, the source of these precursors remains unknown. This study of evaluated the possibility of their bone marrow origin by an examination of the H-2 phenotype of decidual cells in pseudopregnant bone marrow chimeras. These chimeras were produced by repopulating lethally irradiated CBA/J female (H-2k) mice with bone marrow from (CBA/J x C57BL/6J) F1 female (H-2kb) mice. Pseudopregnancy was produced with a hormonal regimen followed by an oil-induced decidual stimulus. Chimerism was evaluated radioautographically by an identification of the donor-specific Kb phenotype on cells with an immunolabeling technique with monospecific anti-H-2 serum followed by radioiodinated protein A. The extent of chimerism as indicated by the degree of Kb labeling on decidual cells as well as macrophages contained within the decidual nodules was quantitatively compared with that seen on splenic lymphocytes. Fair to good chimerism, as reflected by labeling for the donor-specific marker (Kb), was seen on splenic lymphocytes and macrophages within the decidual nodules in 6 out of 11 animals. A similar level of chimerism was detected on decidual cells in all but one of these six, in which case this was low. One animal showed low chimerism in the spleen but good chimerism on the decidual cells. The remaining four mice were nonchimeric for all three cell types. These results indicate that decidual cells and macrophages appearing within the decidual nodules of pseudopregnant mice are ultimate descendants of bone marrow cells

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

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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.

Distinctive genetic activity pattern of the human dental pulp between deciduous and permanent teeth.

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Ji-Hee Kim

Full Text Available Human deciduous and permanent teeth exhibit different developmental processes, morphologies, histological characteristics and life cycles. In addition, their pulp tissues react differently to external stimuli, such as the pulp sensitivity test, dental trauma and pulp therapy materials. These suggest differences in gene expression and regulation, and in this study we compared gene-expression profiles of the human dental pulp from deciduous and permanent teeth. Pulp tissues from permanent premolars and deciduous molars aged 11-14 years were extirpated and mRNA was isolated for cDNA microarray analysis, and quantitative real-time PCR (qPCR. Other teeth were used for immunohistochemical analysis (IHC. Microarray analysis identified 263 genes with a twofold or greater difference in expression level between the two types of pulp tissue, 43 and 220 of which were more abundant in deciduous and permanent pulp tissues, respectively. qPCR analysis was conducted for eight randomly selected genes, and the findings were consistent with the cDNA microarray results. IHC confirmed that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1 was broadly expressed in deciduous dental pulp tissue, but minimally expressed in permanent dental pulp tissue. Immunohistochemical analysis showed that calbindin 1 (CALB1, leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5, and gamma-aminobutyric acid A receptor beta 1 (GABRB1 were abundantly expressed in permanent predentin/odontoblasts, but only minimally expressed in deciduous dental pulp tissue. These results show that deciduous and permanent pulp tissues have different characteristics and gene expression, suggesting that they may have different functions and responses to therapies focused on pulp or dentin regeneration.

Distinctive genetic activity pattern of the human dental pulp between deciduous and permanent teeth.

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Kim, Ji-Hee; Jeon, Mijeong; Song, Je-Seon; Lee, Jae-Ho; Choi, Byung-Jai; Jung, Han-Sung; Moon, Seok Jun; DenBesten, Pamela K; Kim, Seong-Oh

2014-01-01

Human deciduous and permanent teeth exhibit different developmental processes, morphologies, histological characteristics and life cycles. In addition, their pulp tissues react differently to external stimuli, such as the pulp sensitivity test, dental trauma and pulp therapy materials. These suggest differences in gene expression and regulation, and in this study we compared gene-expression profiles of the human dental pulp from deciduous and permanent teeth. Pulp tissues from permanent premolars and deciduous molars aged 11-14 years were extirpated and mRNA was isolated for cDNA microarray analysis, and quantitative real-time PCR (qPCR). Other teeth were used for immunohistochemical analysis (IHC). Microarray analysis identified 263 genes with a twofold or greater difference in expression level between the two types of pulp tissue, 43 and 220 of which were more abundant in deciduous and permanent pulp tissues, respectively. qPCR analysis was conducted for eight randomly selected genes, and the findings were consistent with the cDNA microarray results. IHC confirmed that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was broadly expressed in deciduous dental pulp tissue, but minimally expressed in permanent dental pulp tissue. Immunohistochemical analysis showed that calbindin 1 (CALB1), leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), and gamma-aminobutyric acid A receptor beta 1 (GABRB1) were abundantly expressed in permanent predentin/odontoblasts, but only minimally expressed in deciduous dental pulp tissue. These results show that deciduous and permanent pulp tissues have different characteristics and gene expression, suggesting that they may have different functions and responses to therapies focused on pulp or dentin regeneration.

The local origin of decidual cells in pregnant mice

International Nuclear Information System (INIS)

Zorn, T.M.T.; Abrahamsohn, P.A.; Mariano, M.

1986-01-01

In order to evaluate the participation of extrauterine cells in the formation of mouse antimesometrial decidua, [ 3 H]-thymidine was administered ip on days 1, 5 and 6 of pregnancy and the animals were killed 1 h afterwards. A second group of mice received four ip injections of [ 3 H]-thymidine at 6-h intervals on the 1st day of pregnancy and were killed on the 2nd, 5th or 6th day of pregnancy. A third group of virgin mice in estrus received [ 3 H]-thymidine ip four times at 6-h intervals and was killed 96 h after the first injection. Radioautographs of the uteri showed that few endometrial stomal cells were labelled on the 1st and 2nd day of pregnancy. Although many decidual cells incorporated thymidine on the 5th and 6th day of pregnancy in pulse-labelled animals, only few labelled decidual cells were found on the 5th and 6th day of pregnancy in animals that received several injections of thymidine on the 1st and 2nd day of pregnancy. These results indicate that the antimesometrial decidual cells that develop at the beginning of pregnancy are mostly of local origin. The short-term migration of extraneous cells into the uterus to participate in decidualization is not supported by these data. (author) [pt

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

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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

Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells.

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Blois, Sandra M; Klapp, Burghard F; Barrientos, Gabriela

2011-03-01

Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical for the establishment and maintenance of gestation. The regulatory functions of decidual leukocytes during early pregnancy, particularly dendritic cells (DC) and NK cells, may be important not only for the generation of maternal immunological tolerance but also in the regulation of stromal cell differentiation and the vascular responses associated with the implantation process. However, the specific contributions of DC and NK cells during implantation are still difficult to dissect mainly due to reciprocal regulatory interactions established between them within the decidualizing microenvironment. The present review article discusses current evidence on the regulatory pathways driving decidualization in mice, suggesting that NK cells promote uterine vascular modifications that assist decidual growth but DC directly control stromal cell proliferation, angiogenesis and the homing and maturation of NK cell precursors in the pregnant uterus. Thus, successful implantation appears to result from an interplay between cellular components of the decidualizing endometrium involving immunoregulatory and pro-angiogenic functions of DC and NK cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Expression of epidermal growth factor receptors in human endometrial carcinoma

DEFF Research Database (Denmark)

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...

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.

Immunochemical and ultrastructural assessment of the nature of the pericellular basement membrane of human decidual cells

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Wewer, U M; Faber, M; Liotta, L A

1985-01-01

Human decidual cells of early and late pregnancy were studied immunochemically and ultrastructurally with respect to the presence and nature of pericellular basement membrane material. The most prominent cell type in decidual tissue of both early and late pregnancy were large, mature epithelioid......-linked immunosorbent assay. Biosynthesis of laminin was shown by [35S]methionine labeling of short term organ cultures of decidual tissue followed by immunoprecipation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography. The laminin chains migrated with the apparent molecular weights of 300...... and 200 kilodaltons under reducing conditions. Two other separate populations of cells were apparent in the decidual tissue of early pregnancy. A smaller group of rounded intermediate sized (15 to 25 micron) decidual cells had focal deposits basement membrane immunoreactive material scattered at the cell...

Middle paleolithic human deciduous incisor from Grotta del Cavallo, Italy.

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Fabbri, Pier Francesco; Panetta, Daniele; Sarti, Lucia; Martini, Fabio; Salvadori, Piero A; Caramella, Davide; Fedi, Mariaelena; Benazzi, Stefano

2016-11-01

In this contribution, we present a morphological description and comparative morphometric analysis of Cavallo D, a human tooth unearthed from the Mousterian FIII sublayer of Grotta del Cavallo (Apulia, Italy). We used microCT data to provide a detailed morphological description and morphometric analysis of the Cavallo D human tooth based on traditional diameter measurements and 3D enamel thickness. Moreover, new AMS radiocarbon dating of charcoals from layers FII was carried out. Morphological features observed in Cavallo D align the tooth to Neandertals. Similarly, the large size of the tooth (e.g., BL diameter) and the relatively thinner enamel thickness are typical Neandertal traits. 14 C datings of layer FII attribute the tooth to a time range of 45,600-42,900 cal BP (at 68% level of probability). Up to now, the Rdi 1 Cavallo D represents the most recent Neandertal human remain in southern Italy related to a radiocarbon dated stratigraphy. Moreover, since deciduous teeth have been less investigated than the permanent ones, this contribution brings new data to increase our knowledge on the variability of the Neandertal deciduous dentition. © 2016 Wiley Periodicals, Inc.

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.

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

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:

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

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Haidy El-Azzamy

2017-05-01

Full Text Available Background The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. Methods Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14 or without labor (TNL, n = 15. Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR. Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. Results The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1, galectin-1 (LGALS1, and progestogen-associated endometrial protein (PAEP; the expression of estrogen receptor 1 (ESR1, homeobox A11 (HOXA11, interleukin 1β (IL1B, IL8, progesterone receptor membrane component 2 (PGRMC2, and prostaglandin E synthase (PTGES was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2, CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and

Comparative gene expression analysis of the human periodontal ligament in deciduous and permanent teeth.

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Je Seon Song

Full Text Available There are histological and functional differences between human deciduous and permanent periodontal ligament (PDL tissues. The aim of this study was to determine the differences between these two types of tissue at the molecular level by comparing their gene expression patterns. PDL samples were obtained from permanent premolars (n = 38 and anterior deciduous teeth (n = 31 extracted from 40 healthy persons. Comparative cDNA microarray analysis revealed several differences in gene expression between the deciduous and permanent PDL tissues. These findings were verified by qRT-PCR (quantitative reverse-transcription-polymerase chain reaction analysis, and the areas where genes are expressed were revealed by immunohistochemical staining. The expressions of 21 genes were up-regulated in deciduous relative to PDL tissues, and those of 30 genes were up-regulated in permanent relative to deciduous PDL tissues. The genes that were up-regulated in deciduous PDL tissues were those involved in the formation of the extracellular matrix (LAMC2, LAMB3, and COMP, tissue development (IGF2BP, MAB21L2, and PAX3, and inflammatory or immune reactions leading to tissue degradation (IL1A, CCL21, and CCL18. The up-regulated genes in permanent PDL tissues were related to tissue degradation (IL6 and ADAMTS18, myocontraction (PDE3B, CASQ2, and MYH10, and neurological responses (FOS, NCAM2, SYT1, SLC22A3, DOCK3, LRRTM1, LRRTM3, PRSS12, and ARPP21. The analysis of differential gene expressions between deciduous and permanent PDL tissues aids our understanding of histological and functional differences between them at the molecular level.

Comparative gene expression analysis of the human periodontal ligament in deciduous and permanent teeth.

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Song, Je Seon; Hwang, Dong Hwan; Kim, Seong-Oh; Jeon, Mijeong; Choi, Byung-Jai; Jung, Han-Sung; Moon, Seok Jun; Park, Wonse; Choi, Hyung-Jun

2013-01-01

There are histological and functional differences between human deciduous and permanent periodontal ligament (PDL) tissues. The aim of this study was to determine the differences between these two types of tissue at the molecular level by comparing their gene expression patterns. PDL samples were obtained from permanent premolars (n = 38) and anterior deciduous teeth (n = 31) extracted from 40 healthy persons. Comparative cDNA microarray analysis revealed several differences in gene expression between the deciduous and permanent PDL tissues. These findings were verified by qRT-PCR (quantitative reverse-transcription-polymerase chain reaction) analysis, and the areas where genes are expressed were revealed by immunohistochemical staining. The expressions of 21 genes were up-regulated in deciduous relative to PDL tissues, and those of 30 genes were up-regulated in permanent relative to deciduous PDL tissues. The genes that were up-regulated in deciduous PDL tissues were those involved in the formation of the extracellular matrix (LAMC2, LAMB3, and COMP), tissue development (IGF2BP, MAB21L2, and PAX3), and inflammatory or immune reactions leading to tissue degradation (IL1A, CCL21, and CCL18). The up-regulated genes in permanent PDL tissues were related to tissue degradation (IL6 and ADAMTS18), myocontraction (PDE3B, CASQ2, and MYH10), and neurological responses (FOS, NCAM2, SYT1, SLC22A3, DOCK3, LRRTM1, LRRTM3, PRSS12, and ARPP21). The analysis of differential gene expressions between deciduous and permanent PDL tissues aids our understanding of histological and functional differences between them at the molecular level.

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

Correlation between transvaginal ultrasound measured endometrial thickness and histopathological findings in Turkish women with abnormal uterine bleeding.

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Ozer, Alev; Ozer, Serdar; Kanat-Pektas, Mine

2016-05-01

The present study aims to determine how transvaginal ultrasonography and histopathological examination findings are correlated in a cohort of premenopausal and postmenopausal Turkish women with abnormal uterine bleeding. This is a retrospective review of 350 Turkish women who underwent transvaginal ultrasonography and suction curettage as a result of abnormal uterine bleeding. Sonographic appearance of the endometrium was normal in 244 patients (69.7%), while homogeneous thickening was detected in 47 patients (13.4%) and cystic thickening in 21 patients (6.0%). A sonographic diagnosis of endometrial polyp was made in 38 patients (10.9%). Histopathological analysis of endometrial samplings revealed proliferative endometrium (36%), secretory endometrium (24.6%), decidualization (10.9%), endometrial polyp (8.3%), endometritis (6.8%), endometrial hyperplasia (4.6%), irregular shedding (3.7%), atrophic endometrium (3.1%), endometrial cancer (1.1%) and placental retention (0.9%). The sonographic and histopathological findings correlated significantly (χ(2) = 122 768, P = 0.001; r = 0.215, P = 0.001). Approximately 51% of the women with homogeneous endometrial thickening had proliferative endometrium. Only 44.7% of the women with ultrasonographically visualized endometrial polyps had histopathologically diagnosed endometrial polyps. Nearly 57% of the women with cystic endometrial thickening had proliferative endometrium. If there is no facility for hysteroscopy or hysteroscopy-guided endometrial biopsy for women with abnormal uterine bleeding, transvaginal ultrasonography findings can be efficiently used to make a preliminary diagnosis and, thus, notify the pathologists. © 2016 Japan Society of Obstetrics and Gynecology.

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

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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.

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

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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

Ultrastructural Modifications of Human Endometrium during the Window of Implantation

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Maryam Kabir-Salmani

2008-01-01

Full Text Available The endometrium is a highly dynamic tissue empowered with the capacity to undergo cyclicdramatic changes in response to ovarian steroid hormones, ultimately aiming to create awindow of receptivity for blastocyst implantation. Intensive research has been performed tounderstand and establish morphological and molecular correlates of embryo implantation.However, it still remains a biological mystery particularly in the human, where ethical andmoral constraints prohibit in vivo testing and the establishment of an ideal in vitro modeling.Rodent models of embryo implantation are largely irrelevant because the process variessignificantly from that in humans. Even among primates, subtle differences exist amongspecies. For maternal preparation of implantation, the endometrial epithelium which issurprisingly hostile towards the embryo implantation, acquires functional status receptiveto blastocyst acceptance during a limited period of cycle days, termed as the ‘window ofimplantation (WOI. This review provides currently available information concernedprimarily with the various ultrastructural modifications of endometrium coordinated withinthe WOI that may signify endometrial receptivity. In the following sections, the dominantfeatures of endometrial differentiation during WOI, including transformations of luminalepithelium, endometrial glands, and stromal decidualization will be discussed from themorphological points of view.

Isolation of Mesenchymal Stem Cells from Human Deciduous Teeth Pulp

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Aileen I. Tsai

2017-01-01

Full Text Available This study aimed to identify predictors of success rate of mesenchymal stem cell (MSC isolation from human deciduous teeth pulp. A total of 161 deciduous teeth were extracted at the dental clinic of Chang Gung Memorial Hospital. The MSCs were isolated from dental pulps using a standard protocol. In total, 128 colonies of MSCs were obtained and the success rate was 79.5%. Compared to teeth not yielding MSCs successfully, those successfully yielding MSCs were found to have less severe dental caries (no/mild-to-moderate/severe: 63.3/24.2/12.5% versus 12.5/42.4/42.4%, P<0.001 and less frequent pulpitis (no/yes: 95.3/4.7% versus 51.5/48.5%, P<0.001. In a multivariate regression model, it was confirmed that the absence of dental caries (OR = 4.741, 95% CI = 1.564–14.371, P=0.006 and pulpitis (OR = 9.111, 95% CI = 2.921–28.420, P<0.001 was significant determinants of the successful procurement of MSCs. MSCs derived from pulps with pulpitis expressed longer colony doubling time than pulps without pulpitis. Furthermore, there were higher expressions of proinflammatory cytokines, interleukin- (IL- 6 and monocyte chemoattractant protein- (MCP- 1, P<0.01, and innate immune response [toll-like receptor 1 (TLR1 and TLR8, P<0.05; TLR2, TLR3, and TLR6, P<0.01] in the inflamed than noninflamed pulps. Therefore, a carious deciduous tooth or tooth with pulpitis was relatively unsuitable for MSC processing and isolation.

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.

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

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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.

Elsevier Trophoblast Research Award Lecture: Unique properties of decidual T cells and their role in immune regulation during human pregnancy.

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Tilburgs, T; Claas, F H J; Scherjon, S A

2010-03-01

Maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Most studies focus on decidual NK cells and their interaction with fetal trophoblasts, whereas limited data are available on the mechanisms of fetus specific immune recognition and immune regulation by decidual T cells at the fetal-maternal interface. The aim of this review is to describe the phenotypic characteristics of decidual T cell subsets present at the fetal-maternal interface, their interaction with HLA-C expressed by fetal trophoblasts and their role in immune recognition and regulation at the fetal-maternal interface during human pregnancy. Copyright 2010 Elsevier Ltd. All rights reserved.

Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner.

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Vasilopoulou, E; Loubière, L S; Lash, G E; Ohizua, O; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S Y

2014-06-01

Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. This laboratory-based study used human decidua from first (8-11 weeks; n = 18) and second (12-16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10-) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel(®) was evaluated. Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1, TRβ1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different

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

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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

Progestin and thrombin regulate tissue factor expression in human term decidual cells.

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Lockwood, C J; Murk, W; Kayisli, U A; Buchwalder, L F; Huang, S-T; Funai, E F; Krikun, G; Schatz, F

2009-06-01

Perivascular cell membrane-bound tissue factor (TF) initiates hemostasis via thrombin generation. The identity and potential regulation of TF-expressing cells at the human maternal-fetal interface that confers hemostatic protection during normal and preterm delivery is unclear. The objective of the study were to identify TF-expressing cells at the maternal-fetal interface in term and preterm decidual sections by immunohistochemistry and evaluate progestin, thrombin, TNF-alpha, and IL-1beta effects on TF expression by cultured human term decidual cells (DCs). Serial placental sections were immunostained for TF. Leukocyte-free term DC monolayers were incubated with 10(-8) M estradiol (E2) or E2 plus 10(-7) M medroxyprogestrone acetate (MPA) +/- thrombin or TNF-alpha or IL-1beta. ELISA and Western blotting assessed TF in cell lysates. Quantitative real-time RT-PCR measured TF mRNA levels. Immunolocalized TF in DC membranes in preterm and term placental sections displayed higher Histologic Scores than villous mesenchymal cells (P term placental sections, DC-expressed TF exceeds that of other cell types at the maternal-fetal interface and is localized at the cell membranes in which it can bind to factor VII and meet the hemostatic demands of labor and delivery via thrombin formation. Unlike the general concept that TF is constitutive in cells that highly express it, MPA and thrombin significantly enhanced TF expression in term DC monolayers.

Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua.

Science.gov (United States)

Bulun, S E; Mahendroo, M S; Simpson, E R

1993-06-01

It has been proposed that the biosynthesis of estrogens by the human endometrium may be of physiological significance during the menstrual cycle. Local estrogen production was also suggested to be important in the development of endometrial cancer; however, the presence or absence of aromatase enzyme activity in normal human endometrium is controversial. To address this issue, we used a sensitive technique capable of detecting mRNA transcripts present in only very low copy number. The polymerase chain reaction linked to reverse transcription (RT-PCR) was used to evaluate the presence or absence of aromatase cytochrome P450 (P450arom) transcripts in endometrial tissues (n = 7) and endometrial stromal cells (n = 9) under various culture conditions. RNA was isolated from four proliferative and three secretory tissue samples and from cultured endometrial stromal cells isolated from seven proliferative and two secretory endometria. Five sets of cultures were treated with medroxyprogesterone acetate (MPA), estradiol (E2), and forskolin. Additionally, RNA was isolated from decidualized endometrium obtained from a patient with tubal pregnancy. A single stranded cDNA was synthesized from total RNA using Moloney murine leukemia virus reverse transcriptase and a P450arom-specific oligonucleotide. The single stranded cDNA was used as a template for PCR and was amplified for 20-35 cycles using P450arom-specific primers. RNA from adipose tissue and placenta was amplified to provide positive controls, whereas myometrial RNA was used as a negative control. In two experiments involving two endometrial tissues and three sets of cells in culture, a rat P450arom cRNA was coamplified in each sample as an internal control to demonstrate that the remote possibility of RT-PCR failures in individual test samples cannot account for our negative results. By Southern or slot blot hybridization of the amplified fragments using human and rat P450arom-specific probes, we found no evidence for

Transcriptional factor PU.1 regulates decidual C1q expression in early pregnancy in human

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Priyaa Madhukaran Raj

2015-02-01

Full Text Available C1q is the first recognition subcomponent of the complement classical pathway, which in addition to being synthesized in the liver, is also expressed by macrophages and dendritic cells. Trophoblast invasion during early placentation results in accumulation of debris that triggers the complement system. Hence, both early and late components of the classical pathway are widely distributed in the placenta and decidua. In addition, C1q has recently been shown to significantly contribute to feto-maternal tolerance, trophoblast migration, and spiral artery remodeling, although the exact mechanism remains unknown. Pregnancy in mice, genetically deficient in C1q, mirrors symptoms similar to that of human preeclampsia. Thus, regulated complement activation has been proposed as an essential requirement for normal successful pregnancy. Little is known about the molecular pathways that regulate C1q expression in pregnancy. PU.1, an Ets-family transcription factor, is required for the development of hematopoietic myeloid lineage immune cells, and its expression is tissue- specific. Recently, PU.1 has been shown to regulate C1q gene expression in dendritic cells and macrophages. Here, we have examined if PU.1 transcription factor regulates decidual C1q expression. We used immune-histochemical analysis, PCR and immunostaining to localize and study the gene expression of PU.1 transcription factor in early human decidua. PU.1 was highly expressed at gene and protein level in early human decidual cells including trophoblast and stromal cells. Surprisingly, nuclear as well as cytoplasmic PU.1 expression was observed. Decidual cells with predominantly nuclear PU.1 expression had higher C1q expression. It is likely that nuclear and cytoplasmic PU.1 localization has a role to play in early pregnancy via regulating C1q expression in the decidua during implantation.

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

International Nuclear Information System (INIS)

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

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

Soluble human leukocyte antigen G5 polarizes differentiation of macrophages toward a decidual macrophage-like phenotype.

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Lee, Cheuk-Lun; Guo, YiFan; So, Kam-Hei; Vijayan, Madhavi; Guo, Yue; Wong, Vera H H; Yao, YuanQing; Lee, Kai-Fai; Chiu, Philip C N; Yeung, William S B

2015-10-01

What are the actions of soluble human leukocyte antigen G5 (sHLAG5) on macrophage differentiation? sHLAG5 polarizes the differentiation of macrophages toward a decidual macrophage-like phenotype, which could regulate fetomaternal tolerance and placental development. sHLAG5 is a full-length soluble isoform of human leukocyte antigen implicated in immune tolerance during pregnancy. Low or undetectable circulating level of sHLAG5 in first trimester of pregnancy is associated with pregnancy complications such as pre-eclampsia and spontaneous abortion. Decidual macrophages are located in close proximity to invasive trophoblasts, and are involved in regulating fetomaternal tolerance and placental development. Human peripheral blood monocytes were differentiated into macrophages by treatment with granulocyte macrophage colony-stimulating factor in the presence or absence of recombinant sHLAG5 during the differentiation process. The phenotypes and the biological activities of the resulting macrophages were compared. Recombinant sHLAG5 was produced in Escherichia coli BL21 and the protein identity was verified by tandem mass spectrometry. The expression of macrophage markers were analyzed by flow cytometry and quantitative PCR. Phagocytosis was determined by flow cytometry. Indoleamine 2,3-dioxygenase 1 expression and activity were measured by western blot analysis and kynurenine assay, respectively. Cell proliferation and cell cycling were determined by fluorometric cell proliferation assay and flow cytometry, respectively. Cytokine secretion was determined by cytokine array and ELISA kits. Intracellular cytokine expression was measured by flow cytometry. Cell invasion and migration were determined by trans-well invasion and migration assay, respectively. sHLAG5 drove the differentiation of macrophages with 'immuno-modulatory' characteristics, including reduced expression of M1 macrophage marker CD86 and increased expression of M2 macrophage marker CD163. sHLAG5-polarized

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

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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

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

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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.

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.

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

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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

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

Endometrial preparation with desogestrel before Essure hysteroscopic sterilization: preliminary study.

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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.

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

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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.

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

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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.

Ectopic Hard Tissue Formation by Odonto/Osteogenically In Vitro Differentiated Human Deciduous Teeth Pulp Stem Cells.

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Kim, Seunghye; Song, Je Seon; Jeon, Mijeong; Shin, Dong Min; Kim, Seong-Oh; Lee, Jae Ho

2015-07-01

There have been many attempts to use the pulp tissue from human deciduous teeth for dentin or bone regeneration. The objective of this study was to determine the effects of odonto/osteogenic in vitro differentiation of deciduous teeth pulp stem cells (DTSCs) on their in vivo hard tissue-forming potential. DTSCs were isolated from extracted deciduous teeth using the outgrowth method. These cells were exposed to odonto/osteogenic stimuli for 4 and 8 days (Day 4 and Day 8 groups, respectively), while cells in the control group were cultured in normal medium. The in vitro differentiated DTSCs and the control DTSCs were transplanted subcutaneously into immunocompromised mice with macroporous biphasic calcium phosphate and sacrificed at 8 weeks post-implantation. The effect of odonto/osteogenic in vitro differentiation was evaluated using alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction (RT-PCR). The in vivo effect was evaluated by qualitative RT-PCR, assessment of ALP activity, histologic analysis, and immunohistochemical staining. The amount of hard tissue was greater in Day 4 group than Day 8 group (p = 0.014). However, Day 8 group generated lamellar bone-like structure, which was immunonegative to anti-human dentin sialoprotein with significantly low expression level of DSPP compared with the control group (p = 0.008). This study demonstrates that odonto/osteogenic in vitro differentiation of DTSCs enhances the formation of bone-like tissue, instead of dentin-like tissue, when transplanted subcutaneously using MBCP as a carrier. The odonto/osteogenic in vitro differentiation of DTSCs may be an effective modification that enhances in vivo bone formation by DTSCs.

Novel decidual determinants of recurrent miscarriage

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Weimar, C.H.E.

2013-01-01

The major role of the endometrium and in particular of the human endometrial stromal cells (H-ESCs) is to create a receptive environment for embryo implantation and to support a pregnancy should fertilization occur. H-ESC migration promotes embryo implantation. The primary aim of this thesis is to

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.

Sperm protein 17 is highly expressed in endometrial and cervical cancers

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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

Endometrial cancer.

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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.

Progesterone-associated proteins PP12 and PP14 in the human endometrium.

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Rutanen, E M; Koistinen, R; Seppälä, M; Julkunen, M; Suikkari, A M; Huhtala, M L

1987-01-01

Two proteins, designated as PP12 and PP14 were originally isolated from soluble extracts of the human placenta and its adjacent membranes. We have shown that they are synthesized by decidualized/secretory endometrium and not by placenta. Both proteins occur at high concentrations in human amniotic fluid, which is therefore an excellent source for purification. PP12 is a 34-kDa glycoprotein, which has an N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala. This is identical with that of somatomedin-binding protein purified from the amniotic fluid. PP12 too binds somatomedin-C, or IGF-I (insulin-like growth factor-I). Human secretory endometrium synthesizes and secretes PP12, and progesterone stimulates its secretion. PP14 is a 28-kDa glycoprotein. Its N-terminal sequence shows homology to that of beta-lactoglobulins from various species. We have found PP14 in the human endometrium, serum and milk. Immunologically, PP14 is related to progestagen-associated endometrial protein (PEP), alpha-2 pregnancy-associated endometrial protein (alpha-2, PEG), endometrial protein 15 (EP15), alpha-uterine protein (AUP) and chorionic alpha-2 microglobulin (CAG-2). In ovulatory menstrual cycles, the concentration of PP14 increases in endometrial tissue as the secretory changes advance. In serum, the PP14 concentration begins to rise later than the progesterone levels, and high serum PP14 levels are maintained for the first days of the next cycle. By contrast, no elevation of serum PP14 level is seen in anovulatory cycles. Our results show that progesterone-associated proteins are synthesized by the human endometrium and appear in the peripheral circulation, where they can be quantitatively measured using immunochemical techniques.

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

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

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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.

Involvement of atypical transcription factor E2F8 in the polyploidization during mouse and human decidualization

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Qi, Qian-Rong; Zhao, Xu-Yu; Zuo, Ru-Juan; Wang, Tong-Song; Gu, Xiao-Wei; Liu, Ji-Long; Yang, Zeng-Ming

2015-01-01

Polyploid decidual cells are specifically differentiated cells during mouse uterine decidualization. However, little is known about the regulatory mechanism and physiological significance of polyploidization in pregnancy. Here we report a novel role of E2F8 in the polyploidization of decidual cells in mice. E2F8 is highly expressed in decidual cells and regulated by progesterone through HB-EGF/EGFR/ERK/STAT3 signaling pathway. E2F8 transcriptionally suppresses CDK1, thus triggering the polypl...

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

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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.

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

Prenatal factors associated with the neonatal line thickness in human deciduous incisors.

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Kurek, M; Żądzińska, E; Sitek, A; Borowska-Strugińska, B; Rosset, I; Lorkiewicz, W

2015-06-01

The neonatal line (NNL) is used to distinguish developmental events observed in enamel which occurred before and after birth. However, there are few studies reporting relationship between the characteristics of the NNL and factors affecting prenatal conditions. The aim of the study was to determine prenatal factors that may influence the NNL thickness in human deciduous teeth. The material consisted of longitudinal ground sections of 60 modern human deciduous incisors obtained from full-term healthy children with reported birth histories and prenatal factors. All teeth were sectioned in the labio-lingual plane using diamond blade (Buechler IsoMet 1000). Final specimens were observed using scanning electron microscopy at magnifications 320×. For each tooth, linear measurements of the NNL thickness were taken on its labial surface at the three levels from the cemento-enamel junction. The difference in the neonatal line thickness between tooth types and between males and females was statistically significant. A multiple regression analyses confirmed influence of two variables on the NNL thickness standardised on tooth type and the children's sex (z-score values). These variables are the taking of an antispasmodic medicine by the mother during pregnancy and the season of the child's birth. These two variables together explain nearly 17% of the variability of the NNL. Children of mothers taking a spasmolytic medicine during pregnancy were characterised by a thinner NNL compared with children whose mothers did not take such medication. Children born in summer and spring had a thinner NNL than children born in winter. These results indicate that the prenatal environment significantly contributes to the thickness of the NNL influencing the pace of reaching the post-delivery homeostasis by the newborn's organism. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

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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.

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.

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

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.

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

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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.

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

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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.

A single midcycle dose of levonorgestrel similar to emergency contraceptive does not alter the expression of the L-selectin ligand or molecular markers of endometrial receptivity.

Science.gov (United States)

Palomino, Wilder Alberto; Kohen, Paulina; Devoto, Luigi

2010-10-01

To examine the effects of a single-dose of 1.5 mg of levonorgestrel (commonly used as emergency contraceptive) on endometrial receptivity biomarkers through the oral or vaginal route. Prospective randomized single-blinded trial. Affiliated Hospital and University Research Center. Fertile normal women previously sterilized by tubal ligation. Levonorgestrel (1.5 mg) was administered on the day of LH surge either orally (n = 14) or vaginally (n = 13). Molecular assessment of endometrial progesterone receptors, L-selectin ligand, glicodelin-A and αvβ3 integrin by Immunohistochemistry and reverse transcriptase-polymerase chain reaction. Plasma progesterone concentration and endometrial dating were not different. The pattern of progesterone receptors and glycodelin-A expression was not affected during the early and midsecretory phase. Some endometrial biopsies from the group in which levonorgetrel was orally administered showed areas of glandular atrophy and stromal decidualization. However, the expression of the progesterone receptor, L-selectin ligand, αvβ3 integrin, and glycodelin-A were not different between the groups. Levonorgestrel, given as emergency contraceptive on the day of LH surge, does not disrupt either ovulation or progesterone production by the corpus luteum. The contraceptive mechanism of levonorgestrel at the time of LH surge does not include changes in the progesterone receptors or the endometrial receptivity biomarkers. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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.

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

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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

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

Effect of 4% titanium tetrafluoride solution on the erosion of permanent and deciduous human enamel: an in situ/ex vivo study

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Ana Carolina Magalhães

2009-02-01

Full Text Available This in situ/ex vivo study assessed the effect of titanium tetrafluoride (TiF4 solution on erosion of permanent (P and deciduous (d human enamel. Ten volunteers wore acrylic palatal appliances containing 4 enamel samples, divided into two rows: TiF4 and no - TiF4 (control. Each row contained one deciduous and one permanent enamel sample. During the 1st day, formation of a salivary pellicle was allowed. At the 2nd day, the 4% TiF4 solution was applied on one row (TiF4, while the other row remained untreated (control. From the 3rd until the 7th day, the samples were subjected to erosion by immersion in a cola drink for 5 min, 4 times/day. Enamel alterations were determined by microhardness testing (%SMHC. Data were analyzed using 2 two-way ANOVA and Tukey's post hoc test (α=0.05. The mean %SMHC (±SD amounted to: P (TiF4 - 73.32 ± 5.16 and control - 83.49 ± 4.59 and d (TiF4 - 83.01 ± 7.41 and control - 75.75 ± 2.57. In conclusion, the application of 4% TiF4 solution reduced the softening of permanent enamel but not of deciduous enamel significantly. However, no significant differences were detected between the permanent and deciduous enamel when the factor substrate was considered.

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.

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.

Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice.

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Ricardo C Cavalli

Full Text Available Decidual NK (dNK cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK cells by a combination of hypoxia, TGFß-1 and 5-aza-2'-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells. Here, gene expression profiling shows that CD56Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.

Preclinical Studies of Chemotherapy Using Histone Deacetylase Inhibitors in Endometrial Cancer

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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.

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

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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

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

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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.

Phenotypic and growth characterization of human mesenchymal stem cells cultured from permanent and deciduous teeth

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Revathi Shekar

2012-01-01

Conclusions: Permanent and deciduous teeth are both viable sources of stem cells. The permanent teeth were easier to culture because of a lower chance of contamination with oral microflora. The growth characteristics of the cells obtained from both these sources were similar. However, there was a difference in the ratio of fibroblastoid cells to epithelioid cells between the cultures obtained from the permanent and deciduous teeth.

HLA-G, immunocompetent cells and pregnancy outcome : a case of modulation

NARCIS (Netherlands)

Emmer, Peter Martin

2003-01-01

In this thesis we address the immunomodulatory role of human leukocyte antigen G (HLA-G). The placental trophoblast cells express HLA-G as membrane bound and soluble form (due to alternative splicing) at the fetomaternal interface. HLA-G putatively interacts with the maternal endometrial (decidual)

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

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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....

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

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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.

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...

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...

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...

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.

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

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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.

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)

Decidual cell polyploidization necessitates mitochondrial activity.

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Xinghong Ma

Full Text Available Cellular polyploidy has been widely reported in nature, yet its developmental mechanism and function remain poorly understood. In the present study, to better define the aspects of decidual cell polyploidy, we isolated pure polyploid and non-polyploid decidual cell populations from the in vivo decidual bed. Three independent RNA pools prepared for each population were then subjected to the Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the polyploid populations, as compared to the non-polyploid group. Comparative RT-PCR and in situ hybridization results indeed confirmed differential expressional regulation of several genes between the two populations. Based on functional enrichment analyses, up-regulated polyploidy genes appeared to implicate several functions, which primarily include cell/nuclear division, ATP binding, metabolic process, and mitochondrial activity, whereas that of down-regulated genes primarily included apoptosis and immune processes. Further analyses of genes that are related to mitochondria and bi-nucleation showed differential and regional expression within the decidual bed, consistent with the pattern of polyploidy. Consistently, studies revealed a marked induction of mitochondrial mass and ATP production in polyploid cells. The inhibition of mitochondrial activity by various pharmacological inhibitors, as well as by gene-specific targeting using siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi-nucleation development during in vitro stromal cell decidualization, suggesting mitochondria play a major role in positive regulation of decidual cell polyploidization. Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation.

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.

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

Structure and microstructure of coronary dentin in non-erupted human deciduous incisor teeth

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Costa Luciane R.R S.

2002-01-01

Full Text Available The dentin structure of non-erupted human deciduous mandibular and maxillary central and lateral incisor teeth was studied employing light and scanning electron microscopy. For light microscopy, nitric-acid-demineralized and ground sections were used. The sections were stained by hematoxylin-eosin, picrosirius and azo-carmim methods, and ground specimens were prepared using a carborundum disk mounted in a handpiece. For SEM study, teeth were frozen in liquid nitrogen and fractured at longitudinal and transversal directions. Structurally, demineralization and ground methods revealed tubules with primary and secondary curvatures, canaliculi, giant tubules, interglobular dentin, predentin, and intertubular dentin. Scanning electron microscopy showed three-dimensional aspects of dentinal tubules, canaliculi, peritubular dentin, intertubular dentin, and predentin. This study contributes to knowledge about dentin morphology showing characteristics of teeth not yet submitted to mastication stress.

Role of emmprin in endometrial cancer

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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.

Cryopreserved Dental Pulp Tissues of Exfoliated Deciduous Teeth Is a Feasible Stem Cell Resource for Regenerative Medicine

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Yamaza, Haruyoshi; Akiyama, Kentaro; Hoshino, Yoshihiro; Song, Guangtai; Kukita, Toshio; Nonaka, Kazuaki; Shi, Songtao; Yamaza, Takayoshi

2012-01-01

Human exfoliated deciduous teeth have been considered to be a promising source for regenerative therapy because they contain unique postnatal stem cells from human exfoliated deciduous teeth (SHED) with self-renewal capacity, multipotency and immunomodulatory function. However preservation technique of deciduous teeth has not been developed. This study aimed to evaluate that cryopreserved dental pulp tissues of human exfoliated deciduous teeth is a retrievable and practical SHED source for cell-based therapy. SHED isolated from the cryopreserved deciduous pulp tissues for over 2 years (25–30 months) (SHED-Cryo) owned similar stem cell properties including clonogenicity, self-renew, stem cell marker expression, multipotency, in vivo tissue regenerative capacity and in vitro immunomodulatory function to SHED isolated from the fresh tissues (SHED-Fresh). To examine the therapeutic efficacy of SHED-Cryo on immune diseases, SHED-Cryo were intravenously transplanted into systemic lupus erythematosus (SLE) model MRL/lpr mice. Systemic SHED-Cryo-transplantation improved SLE-like disorders including short lifespan, elevated autoantibody levels and nephritis-like renal dysfunction. SHED-Cryo amended increased interleukin 17-secreting helper T cells in MRL/lpr mice systemically and locally. SHED-Cryo-transplantation was also able to recover osteoporosis bone reduction in long bones of MRL/lpr mice. Furthermore, SHED-Cryo-mediated tissue engineering induced bone regeneration in critical calvarial bone-defect sites of immunocompromised mice. The therapeutic efficacy of SHED-Cryo transplantation on immune and skeletal disorders was similar to that of SHED-Fresh. These data suggest that cryopreservation of dental pulp tissues of deciduous teeth provide a suitable and desirable approach for stem cell-based immune therapy and tissue engineering in regenerative medicine. PMID:23251621

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

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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.

Distinct Transcriptional and Alternative Splicing Signatures of Decidual CD4+ T Cells in Early Human Pregnancy

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Weihong Zeng

2017-06-01

Full Text Available Decidual CD4+ T (dCD4 T cells are crucial for the maternal-fetal immune tolerance required for a healthy pregnancy outcome. However, their molecular and functional characteristics are not well elucidated. In this study, we performed the first analysis of transcriptional and alternative splicing (AS landscapes for paired decidual and peripheral blood CD4+ T (pCD4 T cells in human early pregnancy using high throughput mRNA sequencing. Our data showed that dCD4 T cells are endowed with a unique transcriptional signature when compared to pCD4 T cells: dCD4 T cells upregulate 1,695 genes enriched in immune system process whereas downregulate 1,011 genes mainly related to mRNA catabolic process and the ribosome. Moreover, dCD4 T cells were observed to be at M phase, and show increased activation, proliferation, and cytokine production, as well as display an effector-memory phenotype and a heterogenous nature containing Th1, Th17, and Treg cell subsets. However, dCD4 T cells undergo a comparable number of upregulated and downregulated AS events, both of which are enriched in the genes related to cellular metabolic process. And the changes at the AS event level do not reflect measurable differences at the gene expression level in dCD4 T cells. Collectively, our findings provide a comprehensive portrait of the unique transcriptional signature and AS profile of CD4+ T cells in human decidua and help us gain more understanding of the functional characteristic of these cells during early pregnancy.

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...

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

Energy Technology Data Exchange (ETDEWEB)

Yoo, Jung-Yoon; Kim, Tae Hoon; Lee, Jae Hee [Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI (United States); Dunwoodie, Sally L. [Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010 (Australia); St. Vincent' s Clinical School and the School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales 2033 (Australia); Ku, Bon Jeong, E-mail: bonjeong@cnu.ac.kr [Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon (Korea, Republic of); Jeong, Jae-Wook, E-mail: JaeWook.Jeong@hc.msu.edu [Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, Grand Rapids, MI (United States); Department of Women' s Health, Spectrum Health System, Grand Rapids, MI (United States)

2015-07-10

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

Ectopic decidual reaction mimicking inguinal lymphoma on ultrasound

DEFF Research Database (Denmark)

Lorentzen, C.; Prangsgaard, Tina; Lorentzen, Torben

2014-01-01

Ectopic decidual reaction has been described in various intraperitoneal locations. We present a case of unusual ectopic decidual reaction in the groin mimicking inguinal lymphoma on ultrasound in a pregnant woman. This case contributes evidence illustrating the variability of the clinical...... presentation of ectopic decidual reaction....

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...

Usefulness of MRI in diagnosis of endometrial carcinoma and endometrial hyperplasia

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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.).

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.

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

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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.

Genetics of Endometrial Cancers

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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.

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

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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.

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.

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

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

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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.

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.

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.

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...

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.

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.

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.

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 ...

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

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

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

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.

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 ...

Activation of protein kinase C inhibits synthesis and release of decidual prolactin

International Nuclear Information System (INIS)

Harman, I.; Costello, A.; Ganong, B.; Bell, R.M.; Handwerger, S.

1986-01-01

Activation of calcium-activated, phospholipid-dependent protein kinase C by diacylglycerol and phorbol esters has been shown to mediate release of hormones in many systems. To determine whether protein kinase C activation is also involved in the regulation of prolactin release from human decidual, the authors have examined the effects of various acylglycerols and phorbol esters on the synthesis and release of prolactin from cultured human decidual cells. sn-1,2-Dioctanolyglycerol (diC 8 ), which is known to stimulate protein kinase C in other systems, inhibited prolactin release in a dose-dependent manner with maximal inhibition of 53.1% at 100 μM. Diolein (100 μM), which also stimulates protein kinase C activity in some systems, inhibited prolactin release by 21.3%. Phorbol 12-myristate 13-acetate (PMA), phorbol 12,13-didecanoate, and 4β-phorbol 12,13-dibutyrate, which activate protein kinase C in other systems, also inhibited the release of prolactin, which the protein kinase C inactivate 4α-phorbol-12,13-didecanoate was without effect. The inhibition of prolactin release was secondary to a decrease in prolactin synthesis. Although diC 8 and PMA inhibited the synthesis and release of prolactin, these agents had no effect on the synthesis or release of trichloroacetic acid-precipitable [ 35 S]methionine-labeled decidual proteins and did not cause the release of the cytosolic enzymes lactic dehydrogenase and alkaline phosphatase. DiC 8 and PMA stimulates the specific activity of protein kinase C in decidual tissue by 14.6 and 14.0-fold, respectively. The inhibition of the synthesis and release of prolactin by diC 8 and phorbol esters strongly implicates protein kinase C in the regulation of the production and release of prolactin from the decidua

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.

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.

Pregnancy immunology: decidual immune cells.

Science.gov (United States)

Sanguansermsri, Donruedee; Pongcharoen, Sutatip

2008-01-01

Human pregnancy is a complex process. Placental development depends on the function of secretory molecules produced by placental trophoblast cells as well as by maternal uterine immune cells within the decidua. These decidual immune cells are T cells, natural killer cells, macrophages and dendritic cells. The interactions between the trophoblast cells and the maternal immune cells have an impact on the outcome of the pregnancy. Knowledge about the phenotypes and functions of the maternal immune cells in normal and pathological pregnancies including recurrent spontaneous abortions, preeclampsia and hydatidiform moles may improve our understanding of the immunobiology of the normal pregnancy as a whole and may provide approaches for improving the treatment of pathological pregnancies.

Phenotypic and Proteomic Characteristics of Human Dental Pulp Derived Mesenchymal Stem Cells from a Natal, an Exfoliated Deciduous, and an Impacted Third Molar Tooth

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Gurler Akpinar

2014-01-01

Full Text Available The level of heterogeneity among the isolated stem cells makes them less valuable for clinical use. The purpose of this study was to understand the level of heterogeneity among human dental pulp derived mesenchymal stem cells by using basic cell biology and proteomic approaches. The cells were isolated from a natal (NDPSCs, an exfoliated deciduous (stem cells from human exfoliated deciduous (SHED, and an impacted third molar (DPSCs tooth of three different donors. All three stem cells displayed similar features related to morphology, proliferation rates, expression of various cell surface markers, and differentiation potentials into adipocytes, osteocytes, and chondrocytes. Furthermore, using 2DE approach coupled with MALDI-TOF/TOF, we have generated a common 2DE profile for all three stem cells. We found that 62.3±7% of the protein spots were conserved among the three mesenchymal stem cell lines. Sixty-one of these conserved spots were identified by MALDI-TOF/TOF analysis. Classification of the identified proteins based on biological function revealed that structurally important proteins and proteins that are involved in protein folding machinery are predominantly expressed by all three stem cell lines. Some of these proteins may hold importance in understanding specific properties of human dental pulp derived mesenchymal stem cells.

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.

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.

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

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

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

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

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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.

[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.

Ectopic decidual reaction mimicking irritable bowel syndrome: a case report.

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Soraya Salehgargari

2014-01-01

Full Text Available Ectopic decidualization with gross involvement of the peritoneum is one of the rare findings in pregnant women particularly when ectopic decidualization disseminated as an asymptomatic intra-abdominal nodule. We present here a case of an ectopic decidualization in a 33-year-old pregnant woman with symptoms of irritable bowel syndrome during pregnancy.

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.

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.

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.

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

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.

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

Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. NK cells are important for successful pregnancy. After implantation, NK cells encounter extravillous trophoblast cells and regulate trophoblast invasion. NK cell activity is amongst others regulated by C-type lectin heterodimer (CD94/NKG2) and killer cell immunoglobulin-like (KIR) receptors. KIR expression on decidual NK cells is affected by the presence of maternal HLA-C and biased towards KIR2D expression. However, little is known about NKR expression on eNK cells prior to pregnancy. In this study, matched peripheral and menstrual blood (a source of endometrial cells) was obtained from 25 healthy females with regular menstrual cycles. Menstrual blood was collected during the first 36 h of menstruation using a menstrual cup, a non-invasive technique to obtain endometrial cells. KIR and NKG2 receptor expression on eNK cells was characterized by 10-color flow cytometry, and compared to matched pbNK cells of the same female. KIR and HLA-C genotypes were determined by PCR-SSOP techniques. Anti-CMV IgG antibodies in plasma were measured by chemiluminescence immunoassay. KIR expression patterns of eNK cells collected from the same female do not differ over consecutive menstrual cycles. The percentage of NK cells expressing KIR2DL2/L3/S2, KIR2DL3, KIR2DL1, LILRB1 and/or NKG2A was significantly higher in eNK cells compared to pbNK cells, while no significant difference was observed for NKG2C, KIR2DL1/S1, and KIR3DL1. The NKR repertoire of eNK cells was clearly different from pbNK cells, with eNK cells co-expressing more than three NKR simultaneously. In addition, outlier analysis revealed 8 and 15 NKR

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...

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'.

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 ...

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.

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

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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.

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

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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.

Karakterisasi stem cell pulpa gigi sulung dengan modifikasi enzim tripsin (The characterization of stem cells from human exfoliated deciduous teeth using trypsin enzym

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Tri Wijayanti Puspitasari

2014-06-01

Full Text Available Background: Now a days, treatment in dentistry, using tissue regeneration that based on the stem cells from human exfoliated deciduous teeth (SHED, grows rapidly. For several reason, the isolated and cultured SHED is difficult to be applied in Indonesia, therefore the modification is needed. This difficulties were caused by the pulp anatomy, the heterogeneous populations in the pulp chamber and the limitations of tools and materials at the laboratory. Purpose: This research was aimed to examine that the modifications of isolation and culture technique of SHEDs for characterization by using the marker of CD105. Methods: The research was experimental laboratory with the cross sectional design. The samples were the human exfoliated deciduous teeth from the children patients of Pediatric Dentistry Department of Universitas Airlangga Dental Hospital which matched the criteria. Dental pulps were isolated and cultured by using the modifications of Trypsin enzymes. Results: The healthy SHEDs could be produced from the modifications of isolation and culture and positively shown the expression of marker CD105 which were indicated by the fluorencent microscope. Conclusion: SHED which isolated and cultured by using the modified techniques, positively characterized by using marker CD105.Latar Belakang: Pengobatan kedokteran gigi berkembang dengan pesat terutama di bidang regenerasi jaringan berbasis Stem Cells from Human Exfoliated Deciduous Teeth (SHED. Di Indonesia, isolasi dan kultur SHED sulit sehingga perlu dilakukan modifikasi. Kendala ini muncul karena jaringan pulpa yang kecil, heterogen dan keterbatasan alat dan bahan di laboratorium. Tujuan: Penelitian ini bertujuan untuk meneliti modifikasi pada cara isolasi dan kultur SHED untuk karakterisasi menggunakan maker CD105. Metode: Jenis penelitian ini adalah eksperimental laboratoris dengan rancangan cross sectional. Sampel penelitian adalah gigi sulung dari pasien anak di Klinik Kedokteran Gigi Anak

Extrauterine Low-Grade Endometrial Stromal Sarcoma

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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.

Enamel thickness variation of deciduous first and second upper molars in modern humans and Neanderthals

Czech Academy of Sciences Publication Activity Database

Fornai, C.; Benazzi, S.; Svoboda, Jiří; Pap, I.; Harvati, K.; Weber, G. W.

2014-01-01

Roč. 76, November (2014), s. 83-91 ISSN 0047-2484 Institutional support: RVO:68081758 Keywords : Dental tissue proportions * Tooth wear * Deciduous dentition * Homo neanderthalensis * Homo sapiens * Pleistocene Subject RIV: AC - Archeology, Anthropology, Ethnology OBOR OECD: Archaeology Impact factor: 3.733, year: 2014

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 ...

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 ...

[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.

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

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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.

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

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...

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.

Contrasting ozone sensitivity in related evergreen and deciduous shrubs

International Nuclear Information System (INIS)

Calatayud, Vicent; Marco, Francisco; Cervero, Julia; Sanchez-Pena, Gerardo; Sanz, Maria Jose

2010-01-01

Plant responses to enhanced ozone levels have been studied in two pairs of evergreen-deciduous species (Pistacia terebinthus vs. P. lentiscus; Viburnum lantana vs. V. tinus) in Open Top Chambers. Ozone induced widespread visible injury, significantly reduced CO 2 assimilation and stomatal conductance (g s ), impaired Rubisco efficiency and regeneration capacity (V c,max, J max ) and altered fluorescence parameters only in the deciduous species. Differences in stomatal conductance could not explain the observed differences in sensitivity. In control plants, deciduous species showed higher superoxide dismutase (SOD) activity than their evergreen counterparts, suggesting metabolic differences that could make them more prone to redox imbalances. Ozone induced increases in SOD and/or peroxidase activities in all the species, but only evergreens were able to cope with the oxidative stress. The relevancy of these results for the effective ozone flux approach and for the current ozone Critical Levels is also discussed. - Mediterranean evergreen shrubs have a constitutively higher capacity to tolerate ozone stress than their deciduous relatives.

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)

Analyses of the Erosive Effect of Dietary Substances and Medications on Deciduous Teeth.

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Adrian Lussi

Full Text Available This study aimed at analysing the erosive potential of 30 substances (drinks, candies, and medicaments on deciduous enamel, and analyse the associated chemical factors with enamel dissolution. We analysed the initial pH, titratable acidity (TA to pH 5.5, calcium (Ca, inorganic phosphate (Pi, and fluoride (F concentration, and degree of saturation ((pK -pIHAP, (pK -pIFAP, and (pK-pICaF2 of all substances. Then, we randomly distributed 300 specimens of human deciduous enamel into 30 groups (n = 10 for each of the substances tested. We also prepared 20 specimens of permanent enamel for the sake of comparison between the two types of teeth, and we tested them in mineral water and Coca-Cola®. In all specimens, we measured surface hardness (VHN: Vickers hardness numbers and surface reflection intensity (SRI at baseline (SH baseline and SRI baseline, after a total of 2 min (SH2 min and after 4 min (SH4 min and SRI4 min erosive challenges (60 ml of substance for 6 enamel samples; 30°C, under constant agitation at 95 rpm. There was no significant difference in SH baseline between deciduous and permanent enamel. Comparing both teeth, we observed that after the first erosive challenge with Coca-Cola®, a significantly greater hardness loss was seen in deciduous (-90.2 ± 11.3 VHN than in permanent enamel (-44.3 ± 12.2 VHN; p = 0.007, but no differences between the two types of teeth were observed after two challenges (SH4 min. After both erosive challenges, all substances except for mineral water caused a significant loss in relative surface reflectivity intensity, and most substances caused a significant loss in surface hardness. Multiple regression analyses showed that pH, TA and Ca concentration play a significant role in initial erosion of deciduous enamel. We conclude that drinks, foodstuffs and medications commonly consumed by children can cause erosion of deciduous teeth and erosion is mainly associated with pH, titratable acidity and calcium

Analyses of the Erosive Effect of Dietary Substances and Medications on Deciduous Teeth.

Science.gov (United States)

Lussi, Adrian; Carvalho, Thiago Saads

2015-01-01

This study aimed at analysing the erosive potential of 30 substances (drinks, candies, and medicaments) on deciduous enamel, and analyse the associated chemical factors with enamel dissolution. We analysed the initial pH, titratable acidity (TA) to pH 5.5, calcium (Ca), inorganic phosphate (Pi), and fluoride (F) concentration, and degree of saturation ((pK -pI)HAP, (pK -pI)FAP, and (pK-pI)CaF2) of all substances. Then, we randomly distributed 300 specimens of human deciduous enamel into 30 groups (n = 10 for each of the substances tested. We also prepared 20 specimens of permanent enamel for the sake of comparison between the two types of teeth, and we tested them in mineral water and Coca-Cola®. In all specimens, we measured surface hardness (VHN: Vickers hardness numbers) and surface reflection intensity (SRI) at baseline (SH baseline and SRI baseline), after a total of 2 min (SH2 min) and after 4 min (SH4 min and SRI4 min) erosive challenges (60 ml of substance for 6 enamel samples; 30°C, under constant agitation at 95 rpm). There was no significant difference in SH baseline between deciduous and permanent enamel. Comparing both teeth, we observed that after the first erosive challenge with Coca-Cola®, a significantly greater hardness loss was seen in deciduous (-90.2 ± 11.3 VHN) than in permanent enamel (-44.3 ± 12.2 VHN; p = 0.007), but no differences between the two types of teeth were observed after two challenges (SH4 min). After both erosive challenges, all substances except for mineral water caused a significant loss in relative surface reflectivity intensity, and most substances caused a significant loss in surface hardness. Multiple regression analyses showed that pH, TA and Ca concentration play a significant role in initial erosion of deciduous enamel. We conclude that drinks, foodstuffs and medications commonly consumed by children can cause erosion of deciduous teeth and erosion is mainly associated with pH, titratable acidity and calcium

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

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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.

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

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.

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

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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

Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.

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Sarah A Hamilton

Full Text Available Current therapies for preterm labour (PTL focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface. Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL and term labour (TL, thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL, idiopathic PTL and PTL with infection (PTLI. Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid

Biorhythms, deciduous enamel thickness, and primary bone growth: a test of the Havers-Halberg Oscillation hypothesis.

Science.gov (United States)

Mahoney, Patrick; Miszkiewicz, Justyna J; Pitfield, Rosie; Schlecht, Stephen H; Deter, Chris; Guatelli-Steinberg, Debbie

2016-06-01

Across mammalian species, the periodicity with which enamel layers form (Retzius periodicity) in permanent teeth corresponds with average body mass and the pace of life history. According to the Havers-Halberg Oscillation hypothesis (HHO), Retzius periodicity (RP) is a manifestation of a biorhythm that is also expressed in lamellar bone. Potentially, these links provide a basis for investigating aspects of a species' biology from fossilized teeth. Here, we tested intra-specific predictions of this hypothesis on skeletal samples of human juveniles. We measured daily enamel growth increments to calculate RP in deciduous molars (n = 25). Correlations were sought between RP, molar average and relative enamel thickness (AET, RET), and the average amount of primary bone growth (n = 7) in humeri of age-matched juveniles. Results show a previously undescribed relationship between RP and enamel thickness. Reduced major axis regression reveals RP is significantly and positively correlated with AET and RET, and scales isometrically. The direction of the correlation was opposite to HHO predictions as currently understood for human adults. Juveniles with higher RPs and thicker enamel had increased primary bone formation, which suggests a coordinating biorhythm. However, the direction of the correspondence was, again, opposite to predictions. Next, we compared RP from deciduous molars with new data for permanent molars, and with previously published values. The lowermost RP of 4 and 5 days in deciduous enamel extends below the lowermost RP of 6 days in permanent enamel. A lowered range of RP values in deciduous enamel implies that the underlying biorhythm might change with age. Our results develop the intra-specific HHO hypothesis. © 2016 Anatomical Society.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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.

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.

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

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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.

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.

Atypical endometrial cells and atypical glandular cells favor endometrial origin in Papanicolaou cervicovaginal tests: Correlation with histologic follow-up and abnormal clinical presentations

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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

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.

Contrasting ozone sensitivity in related evergreen and deciduous shrubs

Energy Technology Data Exchange (ETDEWEB)

Calatayud, Vicent, E-mail: vicent@ceam.e [Fundacion CEAM, c/ Charles R. Darwin 14, Parque Tecnologico, 46980 Paterna, Valencia (Spain); Marco, Francisco; Cervero, Julia [Fundacion CEAM, c/ Charles R. Darwin 14, Parque Tecnologico, 46980 Paterna, Valencia (Spain); Sanchez-Pena, Gerardo [SPCAN, Dir. Gral. de Medio Natural y Politica Forestal, Ministerio de Medio Ambiente, y Medio Rural y Marino, Rios Rosas 24, 28003 Madrid (Spain); Sanz, Maria Jose [Fundacion CEAM, c/ Charles R. Darwin 14, Parque Tecnologico, 46980 Paterna, Valencia (Spain)

2010-12-15

Plant responses to enhanced ozone levels have been studied in two pairs of evergreen-deciduous species (Pistacia terebinthus vs. P. lentiscus; Viburnum lantana vs. V. tinus) in Open Top Chambers. Ozone induced widespread visible injury, significantly reduced CO{sub 2} assimilation and stomatal conductance (g{sub s}), impaired Rubisco efficiency and regeneration capacity (V{sub c,max,}J{sub max}) and altered fluorescence parameters only in the deciduous species. Differences in stomatal conductance could not explain the observed differences in sensitivity. In control plants, deciduous species showed higher superoxide dismutase (SOD) activity than their evergreen counterparts, suggesting metabolic differences that could make them more prone to redox imbalances. Ozone induced increases in SOD and/or peroxidase activities in all the species, but only evergreens were able to cope with the oxidative stress. The relevancy of these results for the effective ozone flux approach and for the current ozone Critical Levels is also discussed. - Mediterranean evergreen shrubs have a constitutively higher capacity to tolerate ozone stress than their deciduous relatives.

Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice

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Yanli Li

2015-08-01

Full Text Available The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34 immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA, placental growth factor (PLGF, and VEGF receptor 2 (VEGFR2 were also tested. Serum levels of homocysteine (Hcy, follicle stimulating hormone (FSH, luteinizing hormone (LH, prolactin (PRL, progesterone (P4, and estradiol (E2 were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR and estrogen receptor α (ERα were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

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.

Semi-deciduous forest remnants in Benin: patterns and floristic characterisation

NARCIS (Netherlands)

Adomou, A.C.; Akoegninou, A.; Sinsin, B.; Foucault, de B.; Maesen, van der L.J.G.

2009-01-01

Patterns of semi-deciduous forest are investigated in Benin by means of phytosociological releves and multivariate analyses Species and family importance values are assessed for each forest type The classifications and DCA ordination of 176 semi-deciduous forest releves result in six forest types,

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.

[Conservative treatment of deciduous teeth--a review].

Science.gov (United States)

Magnusson, B

1976-06-01

In all countries with a lack of manpower in dentistry, there is an unfortunate tendency to leave the primary teeth without proper conservative treatment. In addition to toothaches and poor esthetics, a neglected care of the primary dentition may result in several other untoward effects. Decayed deciduous teeth may cause such a discomfort during tooth-brushing that the child is prevented from learning good oral hygiene habits. With bad primary molars the child cannot chew properly, and may have to choose soft and often cariogenic food. When the permanent teeth erupt among the decayed deciduous teeth, there will be a greater chance for them to have carious attacks as well. Premature loss of primary molars may lead to malocclusion. It must also be kept in mind that the treatment of badly decayed teeth, including necessary extractions, may be difficult. This may cause fear of dental treatment. On the basis of current Swedish philosophies of treatment the author surveys various conservative procedures for deciduous teeth-amalgam therapy, stainless steel crowns, composites and disking.

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...

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 ...

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...

Timing of Histologic Progression from Chorio-Deciduitis to Chorio-Deciduo-Amnionitis in the Setting of Preterm Labor and Preterm Premature Rupture of Membranes with Sterile Amniotic Fluid.

Science.gov (United States)

Park, Chan-Wook; Park, Joong Shin; Norwitz, Errol R; Moon, Kyung Chul; Jun, Jong Kwan; Yoon, Bo Hyun

2015-01-01

Histologic chorio-deciduitis and chorio-deciduo-amnionitis (amnionitis) in extra-placental membranes are known to represent the early and advanced stages of ascending intra-uterine infection. However, there are no data in humans about the time required for chorio-deciduitis to develop and for chorio-deciduitis without amnionitis to progress to chorio-deciduitis with amnionitis, and the effect of prolongation of pregnancy on the development of chorio-deciduitis and amnionitis in patients with preterm labor and intact membranes (PTL) and preterm premature rupture of membranes (preterm-PROM). We examined these issues in this study. The study population consisted of 289 women who delivered preterm (133 cases with PTL, and 156 cases with preterm-PROM) and who had sterile amniotic fluid (AF) defined as a negative AF culture and the absence of inflammation as evidenced by a matrix metalloproteinase-8 (MMP-8) level membranes (i.e., inflammation-free extra-placental membranes, choroi-deciduitis only, and chorio-deciduitis with amnionitis) in patients with PTL and preterm-PROM. Amniocentesis-to-delivery interval was longer in cases of chorio-deciduitis with amnionitis than in cases of chorio-deciduitis only in both PTL (median [interquartile-range (IQR)]; 645.4 [319.5] vs. 113.9 [526.9] hours; P = 0.005) and preterm-PROM (131.3 [135.4] vs. 95.2 [140.5] hours; Pmembranes. Moreover, prolongation of pregnancy is an independent predictor of the development of both chorio-deciduitis and amnionitis in cases of PTL with sterile AF.

The effect of stem cell from human exfoliated deciduous teeth on T lymphocyte proliferation.

Science.gov (United States)

Alipour, Razieh; Adib, Minoo; Hashemi-Beni, Batool; Sadeghi, Farzaneh

2014-01-01

Mesenchymal stem cells (MSC), a specific type of adult tissue stem cell; have the immunosuppressive effects that make them valuable targets for regenerative medicine and treatment of many human illnesses. Hence, MSC have been the subject of numerous studies. The classical source of MSC is adult bone marrow (BM). Due to many shortcomings of harvesting MSC from BM, finding the alternative sources for MSC is an urgent. Stem cells from human exfoliated deciduous teeth (SHED) are relative new MSC populations that fulfill these criteria but their potential immunosuppressive effect has not been studied enough yet. Thus, in this work the effect of SHED on the proliferation of in vitro activated T lymphocytes were explored. In this study, both mitogen and alloantigen activated T cells were cultured in the presence of different numbers of SHED. In some co-cultures, activated T cells were in direct contact to MSCs and in other co-cultures; they were separated from SHED by a permeable membrane. In all co-cultures, the proliferation of T cells was measured by ELISA Bromodeoxyuridine proliferation assay. In general, our results showed that SHED significantly suppress the proliferation of activated T cells in a dose-dependent manner. Moreover, the suppression was slightly stronger when MSCs were in physical contact to activated T cells. This study showed that SHED likewise other MSC populations can suppress the activation of T lymphocytes, which can be used instead of BM derived MSCs in many investigational and clinical applications.

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

Relationship of endometrial thickness detected by transvaginal sonography with the results of endometrial biopsy & hysteroscopic directed biopsy in post menopausal bleeding

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Vahid Dastjerdi M

2008-05-01

Full Text Available Background: Post-menopausal hemorrhage is one of the most common complains in gynecologic clinics. More than 60% of these cases have abnormal findings in diagnostic work ups. There is contraversy about the best diagnostic method for evaluating post-menopausal hemorrhage. The aim of this study was to evaluate the results of Trans-Vaginal Ultrasonography and compare its result to ones derived from direct endometrial biopsy and Hysteroscopy findings.Methods: In a cross-sectional study, menopausal women who attended the outpatient clinic of Arash Hospital, Tehran University of medical Sciences, from April 2005 to March 2006 with the complain of hemorrhage were evaluated. In all of these patients, after getting informed consent, Trans-Vaginal Ultrasonography, Dilatation and Curettage and Hysteroscopy were performed.Results: The total number of 90 women was recruited to the study with the age range of 41-80 years. The mean age of participants was 53.84 ± 6 years and 4.3 ± 5.1 years had passed from their menopause. The mean thickness of endometrium, measured by Trans Vaginal ultrasonography was 6.25 ± 3.7 millimeter. In the biopsy derived specimens, the most finding pathological presentation was atrophy (48.9% and the Proliferative endometrium had the second prevalence (36.7%. Atrophy (44.4% and Proliferative endometrium (33.3% were the most prevalent finding in Hysteroscopy. There was a significant difference in endometrial thickness between groups of different pathological findings. A significant difference in endometrial thickness was also seen between groups with different Hysteroscopic finding. By grouping the data according to endometrial thickness, it became evident that endometrial thickness can predict the outcome of endometrial biopsy and Hysteroscopic finding efficiently. We used ROC curves to find the best grouping threshold for endometrial thickness to achieve the best sensitivity and specificity.Conclusion: Measuring the endometrial

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

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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.

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

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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.

Endometrial Cancer Treatment (PDQ®)—Health Professional Version

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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.

Adjuvant radiotherapy for stage I endometrial cancer.

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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.

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

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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.

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.

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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.

Decidual activin: its role in the apoptotic process and its regulation by prolactin.

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Tessier, Christian; Prigent-Tessier, Anne; Bao, Lei; Telleria, Carlos M; Ferguson-Gottschall, Susan; Gibori, Gil B; Gu, Yan; Bowen-Shauver, Jennifer M; Horseman, Nelson D; Gibori, Geula

2003-05-01

Successful pregnancy requires profound differentiation and reorganization of the uterine tissues including, as pregnancy progresses, extensive apoptosis of decidual tissue to accommodate the developing conceptus. We have previously shown a positive correlation between expression of activin A and apoptosis in the decidua and have also shown that expression of activin A occurs at the time when prolactin (PRL) receptors disappear from decidual cells. The goals of this study were to examine whether activin A plays a role in decidual apoptosis and whether expression of activin A in the decidua is regulated by PRL and placental lactogens. Studies were carried out using primary rat decidual cells, a decidual cell line (GG-AD), and PRL null mice. Treatment of decidual cells with activin A significantly increased DNA degradation, caspase 3 activity, and caspase 3 mRNA expression. However, this effect was observed only in the absence of endogenous activin production by these cells. Addition of follistatin to decidual cells that were producing activin A decreased both caspase 3 activity and mRNA expression. Similarly, addition of activin-blocking antibodies to cultures of GG-AD cells, which also produce activin A, caused a reduction in both DNA degradation and caspase 3 activity. PRL and placental lactogens caused an inhibition of activin A mRNA expression in primary decidual cells. Even more convincingly, decidua of PRL null mice expressed abundant activin A at a time when no expression of this hormone is detected in wild-type mice and treatment of PRL null mice with PRL caused a profound inhibition of activin A mRNA expression. In summary, our investigations into the role and regulation of decidual activin have revealed that activin A can induce cell death in the decidua and that its expression is under tight regulation by PRL and placental lactogens.

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

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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

Clinicopathologic Aspects of Endometrial Proliferous Processes in Women of Reproductive Age

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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%.

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.

The evolution of menstruation: a new model for genetic assimilation: explaining molecular origins of maternal responses to fetal invasiveness.

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Emera, Deena; Romero, Roberto; Wagner, Günter

2012-01-01

Why do humans menstruate while most mammals do not? Here, we present our answer to this long-debated question, arguing that (i) menstruation occurs as a mechanistic consequence of hormone-induced differentiation of the endometrium (referred to as spontaneous decidualization, or SD); (ii) SD evolved because of maternal-fetal conflict; and (iii) SD evolved by genetic assimilation of the decidualization reaction, which is induced by the fetus in non-menstruating species. The idea that menstruation occurs as a consequence of SD has been proposed in the past, but here we present a novel hypothesis on how SD evolved. We argue that decidualization became genetically stabilized in menstruating lineages, allowing females to prepare for pregnancy without any signal from the fetus. We present three models for the evolution of SD by genetic assimilation, based on recent advances in our understanding of the mechanisms of endometrial differentiation and implantation. Testing these models will ultimately shed light on the evolutionary significance of menstruation, as well as on the etiology of human reproductive disorders like endometriosis and recurrent pregnancy loss. Copyright © 2012 WILEY Periodicals, Inc.

The evolution of menstruation: A new model for genetic assimilation

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Emera, D.; Romero, R.; Wagner, G.

2012-01-01

Why do humans menstruate while most mammals do not? Here, we present our answer to this long-debated question, arguing that (i) menstruation occurs as a mechanistic consequence of hormone-induced differentiation of the endometrium (referred to as spontaneous decidualization, or SD); (ii) SD evolved because of maternal-fetal conflict; and (iii) SD evolved by genetic assimilation of the decidualization reaction, which is induced by the fetus in non-menstruating species. The idea that menstruation occurs as a consequence of SD has been proposed in the past, but here we present a novel hypothesis on how SD evolved. We argue that decidualization became genetically stabilized in menstruating lineages, allowing females to prepare for pregnancy without any signal from the fetus. We present three models for the evolution of SD by genetic assimilation, based on recent advances in our understanding of the mechanisms of endometrial differentiation and implantation. Testing these models will ultimately shed light on the evolutionary significance of menstruation, as well as on the etiology of human reproductive disorders like endometriosis and recurrent pregnancy loss. PMID:22057551

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

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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.

[Immunomorphologic features of epithelial-stromal relationships at hyperplasia and endometrial carcinoma].

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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.

Increased endometrial thickness in women with hypertension.

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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.

Lipocalin 2 expression is associated with aggressive features of endometrial cancer

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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

[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.

The use of deciduous molars in EPR dose reconstruction

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El-faramawy, N.A.; Wieser, A.

2005-01-01

The use of deciduous teeth in EPR dose reconstruction has the unique potential to measure individual doses that were accumulated in the early childhood in the age up to 12 years. It was found previously that due to the small size of deciduous incisors, the available amount of enamel is not sufficient for EPR measurements. Therefore, dose assessment with deciduous incisors can only be done by measurement of whole teeth, including enamel and dentine. The measurement of whole teeth instead of enamel alone is possibly less reliable for dose reconstruction because the stability of CO 2 - radicals (that are an indicator for the absorbed dose) in biologically active dentine is not known. In the present study naturally loosed deciduous molars were investigated. The feasibility of separating enamel from small size molars was analysed. EPR spectrum parameters of whole molars and separated enamel only were evaluated before and after laboratory irradiation. The EPR signal amplitudes of the CO 2 - and native signals were determined by spectrum deconvolution, in dependence on radiation dose in the range 0.1 - 10 Gy. The fading at room temperature of native and CO 2 - EPR signals was analysed. The detection threshold for absorbed dose in enamel was determined.

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.

International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm: agreement and reliability study.

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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

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

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.

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

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

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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.

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

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

Mouse endometrial stromal cells produce basement-membrane components

DEFF Research Database (Denmark)

Wewer, U M; Damjanov, A; Weiss, J

1986-01-01

During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations. The dec......During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations....... Mouse decidual cells isolated from 6- to 7-day pregnant uteri explanted in vitro continue to synthesize basement-membrane-like extracellular matrix. Using immunohistochemistry and metabolic labeling followed by immunoprecipitation, SDS-PAGE, and fluorography, it was shown that the decidual cells...... to undergo pseudodecidualization. We thus showed that stromal cells from pregnant and nonpregnant mouse uteri synthesize significant amounts of basement-membrane components in vitro, and hence could serve as a good model for the study of normal basement-membrane components....

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.

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

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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

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, ...

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 ...

VEGF blockade inhibits angiogenesis and reepithelialization of endometrium.

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Fan, Xiujun; Krieg, Sacha; Kuo, Calvin J; Wiegand, Stanley J; Rabinovitch, Marlene; Druzin, Maurice L; Brenner, Robert M; Giudice, Linda C; Nayak, Nihar R

2008-10-01

Despite extensive literature on vascular endothelial growth factor (VEGF) expression and regulation by steroid hormones, the lack of clear understanding of the mechanisms of angiogenesis in the endometrium is a major limitation for use of antiangiogenic therapy targeting endometrial vessels. In the current work, we used the rhesus macaque as a primate model and the decidualized mouse uterus as a murine model to examine angiogenesis during endometrial breakdown and regeneration. We found that blockade of VEGF action with VEGF Trap, a potent VEGF blocker, completely inhibited neovascularization during endometrial regeneration in both models but had no marked effect on preexisting or newly formed vessels, suggesting that VEGF is essential for neoangiogenesis but not survival of mature vessels in this vascular bed. Blockade of VEGF also blocked reepithelialization in both the postmenstrual endometrium and the mouse uterus after decidual breakdown, evidence that VEGF has pleiotropic effects in the endometrium. In vitro studies with a scratch wound assay showed that the migration of luminal epithelial cells during repair involved signaling through VEGF receptor 2-neuropilin 1 (VEGFR2-NP1) receptors on endometrial stromal cells. The leading front of tissue growth during endometrial repair was strongly hypoxic, and this hypoxia was the local stimulus for VEGF expression and angiogenesis in this tissue. In summary, we provide novel experimental data indicating that VEGF is essential for endometrial neoangiogenesis during postmenstrual/postpartum repair.

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

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.

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 ...

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

COMPARATIVE STUDY OF ENDOMETRIAL SAMPLING USING PIPELLE WITH HYSTEROSCOPIC-GUIDED BIOPSY

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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.

Abnormal expression of blood group-related antigens in uterine endometrial cancers.

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Tsukazaki, K; Sakayori, M; Arai, H; Yamaoka, K; Kurihara, S; Nozawa, S

1991-08-01

The expression of A, B, and H group antigens, Lewis group antigens (Lewis(a), Lewis(b), Lewis(x), and Lewis(y)), and Lc4 and nLc4 antigens, the precursor antigens of both groups, was examined immunohistochemically with monoclonal antibodies in 9 normal endometria, 6 endometrial hyperplasias, and 31 endometrial cancers. 1) A, B and/or H antigens were detected in endometrial cancers at an incidence of 51.6%, while no distinct localization of these antigens was observed in normal endometria. H antigen, the precursor of A and B antigens, was particularly frequently detected in endometrial cancers. 2) An increased rate of expression of Lewis group antigens, particularly Lewis(b) antigen, was observed in endometrial cancers compared with its expression in normal endometria. 3) Lc4 and nLc4 antigens were detected in endometrial cancers at rates of 41.9% and 38.7%, respectively, these expressions being increased compared with those in normal endometria. 4) These results suggest that a highly abnormal expression of blood group-related antigens in endometrial cancers occurs not only at the level of A, B, and H antigens and Lewis group antigens, but also at the level of their precursor Lc4 and nLc4 antigens. 5) Lewis(a), Lewis(b), and Lc4 antigens, built on the type-1 chain, are more specific to endometrial cancers than their respective positional isomers, Lewis(x), Lewis(y), and nLc4 antigens, built on the type-2 chain.

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.

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.

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

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.)

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

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

Osteogenic differentiation and mineralization of human exfoliated deciduous teeth stem cells on modified chitosan scaffold

Energy Technology Data Exchange (ETDEWEB)

Su, Wen-Ta, E-mail: f10549@ntut.edu.tw [Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan (China); Wu, Pai-Shuen [Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan (China); Ko, Chih-Sheng [PhytoHealth Corporation, Maywufa Biopharma Group, Taipei, Taiwan (China); Huang, Te-Yang [Mackay Memorial Hospital, Taipei, Taiwan (China)

2014-08-01

Stem cells from human exfoliated deciduous teeth (SHEDs) have been considered as alternative sources of adult stem cells in tissue engineering because of their potential to differentiate into multiple cell lineages. Strontium has an important function in bone remodeling because it can simulate bone formation and decrease bone resorption. In this study, the effects of strontium phosphate on the osteogenic differentiation of SHEDs were investigated. Strontium phosphate was found to enhance the osteogenic differentiation of SHEDs with up-regulated osteoblast-related gene expression. The proliferation of SHEDs was slightly inhibited by chitosan scaffolds; however, type-I collagen expression, alkaline phosphatase activity, and calcium deposition on chitosan scaffolds containing strontium were significantly enhanced. Furthermore, cells seeded in a 3D scaffold under dynamic culture at an optimal fluid rate might enhance cellular differentiation than static culture in osteoblastic gene expression. This experiment might provide a useful cell resource and dynamic 3D culture for tissue engineering and bone repair. - Highlights: • SHEDs have been considered as alternative sources of adult stem cells in tissue engineering • Strontium phosphate can enhance the osteogenic differentiation of SHEDs • 3D scaffold under dynamic culture with optimal fluid rate enhance cellular differentiation.

Osteogenic differentiation and mineralization of human exfoliated deciduous teeth stem cells on modified chitosan scaffold

International Nuclear Information System (INIS)

Su, Wen-Ta; Wu, Pai-Shuen; Ko, Chih-Sheng; Huang, Te-Yang

2014-01-01

Stem cells from human exfoliated deciduous teeth (SHEDs) have been considered as alternative sources of adult stem cells in tissue engineering because of their potential to differentiate into multiple cell lineages. Strontium has an important function in bone remodeling because it can simulate bone formation and decrease bone resorption. In this study, the effects of strontium phosphate on the osteogenic differentiation of SHEDs were investigated. Strontium phosphate was found to enhance the osteogenic differentiation of SHEDs with up-regulated osteoblast-related gene expression. The proliferation of SHEDs was slightly inhibited by chitosan scaffolds; however, type-I collagen expression, alkaline phosphatase activity, and calcium deposition on chitosan scaffolds containing strontium were significantly enhanced. Furthermore, cells seeded in a 3D scaffold under dynamic culture at an optimal fluid rate might enhance cellular differentiation than static culture in osteoblastic gene expression. This experiment might provide a useful cell resource and dynamic 3D culture for tissue engineering and bone repair. - Highlights: • SHEDs have been considered as alternative sources of adult stem cells in tissue engineering • Strontium phosphate can enhance the osteogenic differentiation of SHEDs • 3D scaffold under dynamic culture with optimal fluid rate enhance cellular differentiation

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.

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.

Human decidual macrophages and NK cells differentially express Toll-like receptors and display distinct cytokine profiles upon TLR stimulation.

Directory of Open Access Journals (Sweden)

Marion eDuriez

2014-07-01

Full Text Available Maternofetal pathogen transmission is partially controlled at the level of the maternal uterine mucosa at the fetal implantation site (the decidua basalis, where maternal and fetal cells are in close contact. Toll-like receptors (TLRs may play an important role in initiating rapid immune responses against pathogens in the decidua basalis, however the tolerant microenvironment should be preserved in order to allow fetal development. Here we investigated the expression and functionality of TLRs expressed by decidual macrophages (dMs and NK cells (dNKs, the major decidual immune cell populations.We report for the first time that both human dMs and dNK cells express mRNAs encoding TLRs 1-9, albeit with a higher expression level in dMs. TLR2, TLR3 and TLR4 protein expression checked by flow cytometry was positive for both dMs and dNK cells. In vitro treatment of primary dMs and dNK cells with specific TLR2, TLR3, TLR4, TLR7/8 and TLR9 agonists enhanced their secretion of pro- and anti-inflammatory cytokines, as well as cytokines and chemokines involved in immune cell crosstalk. Only dNK cells released IFN-γ, whereas only dMs released IL-1β, IL-10 and IL-12. TLR9 activation of dMs resulted in a distinct pattern of cytokine expression compared to the other TLRs. The cytokine profiles expressed by dMs and dNK cells upon TLR activation are compatible with maintenance of the fetotolerant immune environment during initiation of immune responses to pathogens at the maternofetal interface.

Progesterone resistance in endometriosis

DEFF Research Database (Denmark)

Patel, Bansari G; Rudnicki, Martin; Yu, Jie

2017-01-01

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women...... with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment...... renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone resistant state...

EARLY RECURRENCE OF WELL-DIFFERENTIATED ENDOMETRIAL CANCER (A CASE REPORT

Directory of Open Access Journals (Sweden)

N. E. Levchrnko

2017-01-01

Full Text Available Endometrial cancer is the 6-th most common malignancy in women worldwide, accounting for about 4.8 % of all female cancers. The treatment of recurrent endometrial cancer remains a major challenge. Some endometrial cancer recurrences, for example vaginal stump recurrence, are reported to be effectively treated with surgical resection and radiation therapy. Early recurrence of early-stage well-differentiated endometrial cancer is uncommon. Case report. Herein we report a rare case of recurrent well-differentiated endometrial cancer in a 65-year-old woman. The patient had recurrence 10 months after laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Recurrent endometrial tumor with extension into the rectosigmoid colon, urinary bladder and the right ureter manifested itself clinically with severe pain requiring the use of opioids. The recurrent tumor was removed. Resection of the bladder, left ureter and upper ampular rectum was followed by anastomosis. The patient received multiple cycles of chemotherapy. Conclusion. Compliance with the principles of ablastics during the laparoscopic or laparotomic surgery helps to avoid recurrence in patients with prognostically favorable cancer. In case of recurrence, combined operations are the only possible chance of improving survival of patients with locally advanced or recurrent tumors, which are insensitive to chemoradiotherapy.

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 ...

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 ...

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

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.

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.

MR findings of ruptured endometrial cyst: Comparison with tubo-ovarian abscess

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Shigeru, E-mail: shig.suz@gmail.com [Department of Radiology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan); Yasumoto, Mayumi, E-mail: Mayumihoo@yahoo.co.jp [Department of Radiology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan); Matsumoto, Reiko, E-mail: rad@saitama-med.jrc.or.jp [Department of Radiology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan); Andoh, Akihiko, E-mail: a-andoh@silk.plala.or.jp [Department of Obstetrics and Gynecology, Saitama Red Cross Hospital, 8-3-33 Kamiochiai, Chuo-ku, Saitama, 338-8553 (Japan)

2012-11-15

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. {chi}{sup 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.

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

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.

Modified Willet's appliance for bilateral loss of multiple deciduous molars: a case report.

Science.gov (United States)

Dhindsa, A; Pandit, I K

2008-09-01

No other factor plays a more significant role in preventive and interceptive dentistry than the preservation of deciduous dentition till its normal time of exfoliation. Premature loss of a deciduous tooth or a group of teeth might lead to wide range of implications. When the deciduous second molar is lost before the eruption of first permanent molar, intra-alveolar type of space maintainer is indicated. But in cases of bilateral loss of these teeth the conventional design generally poses a variety of problems. Thus, the conventional designs are required to be modified according to the needs of the patient. Therefore, this paper describes an entirely new design of the Willet's appliance in cases of bilateral loss of deciduous molars before the eruption of first permanent molar.

Taxonomic differences in deciduous upper second molar crown outlines of Homo sapiens, Homo neanderthalensis and Homo erectus.

Science.gov (United States)

Bailey, Shara E; Benazzi, Stefano; Souday, Caroline; Astorino, Claudia; Paul, Kathleen; Hublin, Jean-Jacques

2014-07-01

A significant number of Middle to Late Pleistocene sites contain primarily (and sometimes only) deciduous teeth (e.g., Grotta del Cavallo, Mezmaiskaya, Blombos). Not surprisingly, there has been a recent renewed interest in deciduous dental variation, especially in the context of distinguishing Homo neanderthalensis and Homo sapiens. Most studies of the deciduous dentition of fossil hominins have focused on standard metrical variation but morphological (non-metric and morphometric) variation also promises to shed light on long standing taxonomic questions. This study examines the taxonomic significance of the crown outline of the deciduous upper second molar through principal components analysis and linear discriminant analysis. We examine whether or not the crown shape of the upper deciduous second molar separates H. neanderthalensis from H. sapiens and explore whether it can be used to correctly assign individuals to taxa. It builds on previous studies by focusing on crown rather than cervical outline and by including a large sample of geographically diverse recent human populations. Our samples include 17 H. neanderthalensis, five early H. sapiens, and 12 Upper Paleolithic H. sapiens. In addition, we include two Homo erectus specimens in order to evaluate the polarity of crown shape differences observed between H. neanderthalensis and H. sapiens. Our results show that crown outline shape discriminates H. sapiens and H. neanderthalensis quite well, but does not do well at distinguishing H. erectus from H. sapiens. We conclude that the crown outline shape observed in H. sapiens is a primitive retention and that the skewed shape observed in H. neanderthalensis is a derived condition. Finally, we explore the phylogenetic implications of the results for the H. erectus molars. Copyright © 2014 Elsevier Ltd. All rights reserved.

Indoleamine 2,3-Dioxygenase Is Dispensable for The Immunomodulatory Function of Stem Cells from Human Exfoliated Deciduous Teeth.

Science.gov (United States)

Alipour, Razieh; Masoumi Karimi, Masoumeh; Hashemi-Beni, Batool; Adib, Minoo; Sereshki, Nasrin; Sadeghi, Farzaneh

2017-01-01

In this study, we sought to better understand the immunoregulatory function of stem cells derived from human exfoliated deciduous teeth (SHED). We studied the role of the interferon gamma (IFN-γ)-indoleamine 2,3-dioxygenase (IDO)-axis in immunoregulation of SHED compared to bone marrow derived mesenchymal stem cells (BMMSCs) under the same conditions. In this cross-sectional study, recently isolated human T cells were stimulated either by mitogen or inactivated allogeneic peripheral blood mononuclear cells (PBMCs). These T cells were subsequently co-cultured with, either SHED or BMMSCs in the presence or absence of 1-methyl-tryptophan (1-MT) or neutralizing anti- human-IFN-γ antibodies. In all co-cultures we evaluated lymphocyte activation as well as IDO activity. SHED, similar to conventional BMMSCs, had anti-proliferative effects on stimulated T cells and reduced their cytokine production. This property of SHED and BMMSCs was changed by IFN-γ neutralization. We detected IDO in the immunosuppressive supernatant of all co-cultures. Removal of IDO decreased the immunosuppression of BMMSCs. SHED, like BMMSCs, produced the IDO enzyme. Although IFN-γ is one of inducer of IDO production in SHED, these cells were not affected by IFN-γ in the same manner as BMMSCs. Unlike BMMSCs, the IDO enzyme did not contribute to their immunosuppression and might have other cell-type specific roles.

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

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 ...

Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions

NARCIS (Netherlands)

Plaisier, M.; Dennert, I.; Rost, E.; Koolwijk, P.; Hinsbergh, V.W.M. van; Helmerhorst, F.M.

2009-01-01

BACKGROUND : Decidual vascular development is important for implantation. This study analysed decidual vascular adaptation to implantation in correlation with miscarriage in decidual secretory endometrium (DSE), decidua parietalis (DP) and decidua basalis (DB) of miscarriage patients and matched

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

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

Supragingival Microbial Profiles of Permanent and Deciduous Teeth in Children with Mixed Dentition.

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Weihua Shi

Full Text Available The present study was designed to investigate the microbial profiles of teeth in different locations in mixed-dentition-stage children, and to compare the microbiomes of permanent and deciduous teeth in the same healthy oral cavity.Supragingival plaque samples of teeth in various locations-the first permanent molars, deciduous molars, deciduous canines and incisors and permanent incisors-were collected from 20 healthy mixed-dentition-stage children with 10-12 permanent teeth erupted. Plaque DNA was extracted, and the V3-V4 hypervariable region of the bacterial 16S rRNA gene was amplified and subjected to sequencing.On average, 18,051 high-quality sequences per sample were generated. Permanent tooth sites tended to host more diverse bacterial communities than those of deciduous tooth sites. A total of 12 phyla, 21 classes, 38 orders, 66 families, 74 genera were detected ultimately. Five predominant phyla (Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria and Actinobacteria were highly variable among sites. Of 26 genera with a mean relative abundance of >0.1%, 16 showed significant differences in relative abundance among the groups. More than 20% of the total operational taxonomical units were detected only in permanent or deciduous teeth. The variation in the microbial community composition was due mainly to permanent teeth being enriched in Actinomyces and deciduous teeth in Treponema. The core microbiome of supragingival plaque in mixed dentition comprised 19 genera with complex correlationships.Our results suggest differences in microbial diversity and composition between permanent and deciduous teeth sites in mixed dentition. Moreover, the core microbiome of these sites was determined. These findings enhance our understanding of the development of the native oral microbiota with age.

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

[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.

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

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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.

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.

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.

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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

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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....

Enamel hypoplasia in deciduous teeth of great apes: do differences in defect prevalence imply differential levels of physiological stress?

Science.gov (United States)

Lukacs, J R

1999-11-01

This paper presents new data on enamel hypoplasia in the deciduous canine teeth of great apes. The enamel defect under consideration is known as localized hypoplasia of primary canines (LHPC), and is characterized by an area of thin or missing enamel on the labial surface of deciduous canine teeth (Skinner [1986a] Am. J. Phys. Anthropol. 69:59-69). Goals of this study are: 1) to determine if significant differences in the frequency of LHPC occur among three genera of great apes, and 2) to evaluate variation in LHPC prevalence among great apes as evidence of differential physiological stress. Infant and juvenile apes with deciduous teeth were examined at the Cleveland Museum of Natural History (n = 100) and at the Smithsonian Institution, National Museum of Natural History (n = 36). Deciduous teeth were observed under oblique incandescent light, with the naked eye and with a 10x hand lens. Enamel hypoplasia was scored using Federation Dentaire International (FDI)-Defects of Dental Enamel (DDE) standards. Hypoplasias were recorded by drawing defect location and size on a dental chart, and by measuring defect size and location with Helios needlepoint dial calipers. The prevalence of LHPC is reported by genus and sex, using two approaches: 1) the frequency of affected individuals-those having one or more deciduous canine teeth scored positive for LHPC; and 2) the number of canine teeth scored positive for LHPC as a percentage of all canine teeth observed. Variation in defect size and location will be described elsewhere. Localized hypoplasia of primary canine teeth was found in 62.5% of 128 individual apes, and in 45.5% of 398 great ape deciduous canines. As in humans, LHPC is the most common form of enamel hypoplasia in deciduous teeth of great apes, while LEH is rare or absent. The distribution and pattern of expression of LHPC in great apes is similar to that described in humans: side differences are not significant, but mandibular canines exhibit the defect two to

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

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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.

Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer

DEFF Research Database (Denmark)

Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian

2015-01-01

PURPOSE: We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study. METHODS: Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age...... with use of low-dose aspirin (OR 0.97, 95 % CI 0.89-1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91-1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk...... associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70-0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82-0.99). CONCLUSIONS: We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some...

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

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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.

Allogeneic stem cells derived from human exfoliated deciduous teeth (SHED for the management of periapical lesions in permanent teeth: Two case reports of a novel biologic alternative treatment

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Madu Ghana Shyam Prasad

2017-06-01

Full Text Available Stem cells are the pluripotent cells that have the capacity to differentiate into other specialized cells. Recently, many experiments have been conducted to study the potentiality of stem cells in the tissue regeneration. We report two cases treated utilizing stem cells from human exfoliated deciduous teeth (SHED in the management of periapical lesions in permanent teeth. Two normal human deciduous teeth from children, 7‒8 years of age, were collected to isolate stem cells. Two patients, one with periapical pathology alone and the other with periapical lesion along with an open apex in young permanent teeth, were selected for the study. After initial debridement of the root canals, homing of SHED was carried out and the access cavity was sealed using glass-ionomer cement. Clinical examination after 7 days, 30 days, 90 days, 180 days and 365 days revealed no symptoms. Closure of open apex and periapical tissue healing were observed radiographically at one-month review and maintained until 365-day review. Positive response to electric pulp testing was recorded for the treated teeth from the 3- to 12-month follow-ups. The treated cases demonstrated complete resolution of periapical radiolucency in a span of 30 days, which was faster than the conventional methods. SHED could be considred effective in treating the periapical lesions and open apex in permanent teeth.

[Early deciduous tooth loss--the mature or immature eruption of their permanent successors].

Science.gov (United States)

Czecholinski, J A; Kahl, B; Schwarze, C W

1994-04-01

On the basis of 147 panoramic radiographs of 49 patients, this study investigated the influence of the premature loss of deciduous teeth on the formation of their permanent successors at the time of their eruption. Furthermore the study investigated the eruptive movement of the successor teeth at the time of eruption. In addition to detecting the accelerated emergence of still immature successor premolars, the study also determined that the extraction ot the deciduous molars before the age of eight years delayed the eruption of the permanent successors given the absence of an infected deciduous tooth with abscess formation. In relation to the eruptive movement of the permanent molars due to the premature loss of the second deciduous molar, the study ascertained a mesial movement of the first permanent molars and an accelerated eruption of the second permanent molars.

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...

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.

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 ...

Morphological, chemical and structural characterisation of deciduous enamel: SEM, EDS, XRD, FTIR and XPS analysis.

Science.gov (United States)

Zamudio-Ortega, C M; Contreras-Bulnes, R; Scougall-Vilchis, R J; Morales-Luckie, R A; Olea-Mejía, O F; Rodríguez-Vilchis, L E

2014-09-01

The purpose of this study was to characterise the enamel surface of sound deciduous teeth in terms of morphology, chemical composition, structure and crystalline phases. The enamel of 30 human deciduous teeth was examined by: Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDS), X-ray Powder Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS). Chemical differences between incisors and canines were statistically evaluated using the Mann-Whitney U test (p ≤ 0.05). Three enamel patterns were observed by SEM: 'mostly smooth with some groves', 'abundant microporosities' and 'exposed prisms'. The average Ca/P molar ratios were 1.37 and 1.03 by EDS and XPS, respectively. The crystallite size determined by XRD was 210.82 ± 16.78 Å. The mean ratio between Ca bonded to phosphate and Ca bonded to hydroxyl was approximately 10:1. The enamel of sound deciduous teeth showed two main patterns: 'mostly smooth with some groves' and 'abundant microporosities'. 'Exposed prisms' was a secondary pattern. There were slight variations among the Ca/P molar ratios found by EDS and XPS, suggesting differences in the mineral content from the enamel surface to the interior. The crystalline phases found in enamel were hydroxyapatite and carbonate apatite, with major type B than type A carbonate incorporation.

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

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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

Endometrial Receptivity and its Predictive Value for IVF/ICSI-Outcome.

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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.

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.

Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment.

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Ballard, Karen S; Homesley, Howard D; Hodson, Charles; Presant, Cary A; Rutledge, James; Hallquist, Allan; Perree, Mathieu

2010-03-01

The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

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Halima Rakhila

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

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

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

2014-01-01

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

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.

Estimates of ion sources in deciduous and coniferous throughfall

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Puckett, L.J.

1990-01-01

Estimates of external and internal sources of ions in net throughfall deposition were derived for a deciduous and coniferous canopy by use of multiple regression. The externel source component appears to be dominated by dry deposition of Ca2+, SO2 and NO3- during dormant and growing seasons for the two canopy types. Increases in the leaching rates of K+ and Mg2+ during the growing season reflect the presence of leaves in the deciduous canopy and increased physiological activity in both canopies. Internal leaching rates for SO42- doubled during the growing season presumably caused by increased physiological activity and uptake of SO2 through stomates. Net deposition of SO42- in throughfall during the growing season appears highly dependent on stomatal uptake of SO2. Estimates of SO2 deposition velocities were 0.06 cm s-1 and 0.13 cm s-1 for the deciduous and coniferous canopies, respectively, during the dormant season, and 0.30 cm s-1 and 0.43 cm s-1 for the deciduous and coniferous canopies, respectively, during the growing season. For the ions of major interest with respect to ecosystem effects, namely H+, NO3- and SO42-, precipitation inputs generally outweighed estimates of dry deposition input. However, net throughfall deposition of NO3- and SO42- accounted for 20-47 and 34-50 per cent, respectively, of total deposition of those ions. Error estimates of ion sources were at least 50-100 per cent and the method is subject to several assumptions and limitations.

Performance analysis of deciduous morphology for detecting biological siblings.

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Paul, Kathleen S; Stojanowski, Christopher M

2015-08-01

Family-centered burial practices influence cemetery structure and can represent social group composition in both modern and ancient contexts. In ancient sites dental phenotypic data are often used as proxies for underlying genotypes to identify potential biological relatives. Here, we test the performance of deciduous dental morphological traits for differentiating sibling pairs from unrelated individuals from the same population. We collected 46 deciduous morphological traits for 69 sibling pairs from the Burlington Growth Centre's long term Family Study. Deciduous crown features were recorded following published standards. After variable winnowing, inter-individual Euclidean distances were generated using 20 morphological traits. To determine whether sibling pairs are more phenotypically similar than expected by chance we used bootstrap resampling of distances to generate P values. Multidimensional scaling (MDS) plots were used to evaluate the degree of clustering among sibling pairs. Results indicate an average distance between siblings of 0.252, which is significantly less than 9,999 replicated averages of 69 resampled pseudo-distances generated from: 1) a sample of non-relative pairs (P < 0.001), and 2) a sample of relative and non-relative pairs (P < 0.001). MDS plots indicate moderate to strong clustering among siblings; families occupied 3.83% of the multidimensional space on average (versus 63.10% for the total sample). Deciduous crown morphology performed well in identifying related sibling pairs. However, there was considerable variation in the extent to which different families exhibited similarly low levels of phenotypic divergence. © 2015 Wiley Periodicals, Inc.

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 ...

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

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.

MORPHOLOGICAL RESEARCH ON FREE-RESIDUE OXIDATION PROCESSES IN CASES OF DECIDUAL CELLS OF PLACENTA IN CHORIOAMNIONOTIS AND BASAL DECIDUITIS COMBINED WITH IRON-DEFICIENCY ANEMIA IN THE PREGNANT

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V. V. Ilika

2017-07-01

Full Text Available Background. The oxidative modification of proteins is lately pivotal to pathologists and it is a new way of research on different pathological conditions, as well as the diagnostics of inflammation processes in placenta. Objective. The study was aimed at the research of nitro peroxides and establishing the specific features of oxidative modification of proteins in inflammation of placenta with iron deficient anaemia in the pregnant. Methods. Сhemiluminescent and histochemical technique (with bromphenol blue on ‘acidic’ and ‘basic’ proteins according to Mikel Calvo was applied. Results. The intensity of nitro peroxides glow in chorioamnionitis and basal deciduitis increased in comparison with the samples of physiological and iron deficient anaemia gestation. At the same time in chorioamnionitis the glow intensity is higher than in basal deciduitis. Due to the results of immune histochemical technique held while analysing the samples, together with chorioamnionitis and basal deciduitis the R/B increases and in basal deciduitis the rate, is probably, higher, than in chorioamnionitis. At the same time, the extent of oxidative modification of proteins in cases of inflammation with iron deficient anaemia in the pregnant is on the average higher than with no iron deficient anaemia in the pregnant. Conclusions. High level of nitro peroxides in placentae basal plate in secundines inflammation, the increase in R/B rate, in other words the prevalence of ‘acidic’ proteins over ‘basic’ ones, is evidenced due to the increase of the intensity of oxidative modification processes of proteins in cases of deciduitis.

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Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development.

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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

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

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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.

Similar variation in carbon storage between deciduous and evergreen treeline species across elevational gradients.

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Fajardo, Alex; Piper, Frida I; Hoch, Günter

2013-08-01

The most plausible explanation for treeline formation so far is provided by the growth limitation hypothesis (GLH), which proposes that carbon sinks are more restricted by low temperatures than by carbon sources. Evidence supporting the GLH has been strong in evergreen, but less and weaker in deciduous treeline species. Here a test is made of the GLH in deciduous-evergreen mixed species forests across elevational gradients, with the hypothesis that deciduous treeline species show a different carbon storage trend from that shown by evergreen species across elevations. Tree growth and concentrations of non-structural carbohydrates (NSCs) in foliage, branch sapwood and stem sapwood tissues were measured at four elevations in six deciduous-evergreen treeline ecotones (including treeline) in the southern Andes of Chile (40°S, Nothofagus pumilio and Nothofagus betuloides; 46°S, Nothofagus pumilio and Pinus sylvestris) and in the Swiss Alps (46°N, Larix decidua and Pinus cembra). Tree growth (basal area increment) decreased with elevation for all species. Regardless of foliar habit, NSCs did not deplete across elevations, indicating no shortage of carbon storage in any of the investigated tissues. Rather, NSCs increased significantly with elevation in leaves (P treeline species are sink limited when faced with decreasing temperatures. Despite the overall higher requirements of deciduous tree species for carbon storage, no indication was found of carbon limitation in deciduous species in the alpine treeline ecotone.

The role of miRNAs in endometrial cancer.

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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.

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

Global Endometrial Ablation in the Presence of Essure® Microinserts

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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

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.

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

Are preoperative histology and MRI useful for classification of endometrial cancer risk?

International Nuclear Information System (INIS)

Body, Noemie; Lavoué, Vincent; De Kerdaniel, Olivier; Foucher, Fabrice; Henno, Sébastien; Cauchois, Aurélie; Laviolle, Bruno; Leblanc, Marc; Levêque, Jean

2016-01-01

The 2010 guidelines of the French National Cancer Institute (INCa) classify patients with endometrial cancer into three risk groups for lymph node invasion and recurrence on the basis of MRI and histological analysis of an endometrial specimen obtained preoperatively. The classification guides therapeutic choices, which may include pelvic and/or para-aortic lymphadenectomy. The purpose of this study was to evaluate the diagnostic performance of preoperative assessment to help identify intermediate- or high-risk patients requiring lymphadenectomy. The study included all patients who underwent surgery for endometrial cancer between January 2010 and December 2013 at either Rennes University Hospital or Vannes Regional Hospital. The criteria for eligibility included a preoperative assessment with MRI and histological examination of an endometrial sample. A histological comparison was made between the preoperative and surgical specimens. Among the 91 patients who underwent a full preoperative assessment, the diagnosis of intermediate- or high-risk endometrial cancer was established by MRI and histology with a sensitivity of 70 %, specificity of 82 %, positive predictive value (PPV) of 87 %, negative predictive value (NPV) of 61 %, positive likelihood ratio (LR+) of 3.8 and negative likelihood ratio (LR-) of 0.3. The risk group was underestimated in 32 % of patients and overestimated in 7 % of patients. MRI underestimated endometrial cancer stage in 20 % of cases, while endometrial sampling underestimated the histological type in 4 % of cases and the grade in 9 % of cases. The preoperative assessment overestimated or underestimated the risk of recurrence in nearly 40 % of cases, with errors in lesion type, grade or stage. Erroneous preoperative risk assessment leads to suboptimal initial surgical management of patients with endometrial cancer

Modified Willet′s appliance for bilateral loss of multiple deciduous molars: A case report

OpenAIRE

Dhindsa A; Pandit I

2008-01-01

No other factor plays a more significant role in preventive and interceptive dentistry than the preservation of deciduous dentition till its normal time of exfoliation. Premature loss of a deciduous tooth or a group of teeth might lead to wide range of implications. When the deciduous second molar is lost before the eruption of first permanent molar, intra-alveolar type of space maintainer is indicated. But in cases of bilateral loss of these teeth the conventional design generally poses a va...

Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers.

Science.gov (United States)

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.

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....

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....

Modified Willet′s appliance for bilateral loss of multiple deciduous molars: A case report

Directory of Open Access Journals (Sweden)

Dhindsa A

2008-09-01

Full Text Available No other factor plays a more significant role in preventive and interceptive dentistry than the preservation of deciduous dentition till its normal time of exfoliation. Premature loss of a deciduous tooth or a group of teeth might lead to wide range of implications. When the deciduous second molar is lost before the eruption of first permanent molar, intra-alveolar type of space maintainer is indicated. But in cases of bilateral loss of these teeth the conventional design generally poses a variety of problems. Thus, the conventional designs are required to be modified according to the needs of the patient. Therefore, this paper describes an entirely new design of the Willet′s appliance in cases of bilateral loss of deciduous molars before the eruption of first permanent molar.

File list: Oth.Utr.20.AllAg.Endometrial_stromal_cells [Chip-atlas[Archive

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File list: Oth.Utr.50.AllAg.Endometrial_stromal_cells [Chip-atlas[Archive

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File list: Oth.Utr.10.AllAg.Endometrial_stromal_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

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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.

Deciduous molar hypomineralization and molar incisor hypomineralization

NARCIS (Netherlands)

Elfrink, M.E.C.; ten Cate, J.M.; Jaddoe, V.W.V.; Hofman, A.; Moll, H.A.; Veerkamp, J.S.J.

2012-01-01

This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life until young adulthood. This study focused on the relationship between Deciduous Molar Hypomineralization (DMH) and Molar Incisor Hypomineralization (MIH). First permanent molars develop

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.)

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...

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)

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.

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.

Anti-dentine Salivary SIgA in young adults with a history of dental trauma in deciduous teeth

Directory of Open Access Journals (Sweden)

Gabriela Fleury SEIXAS

2015-01-01

Full Text Available Anti-dentin autoantibodies are associated with inflammatory root resorption in permanent teeth and are modulated by dental trauma and orthodontic force. However, it is not known whether deciduous tooth trauma can stimulate the development of a humoral immune response against dentin. The aim of this study was to evaluate the levels of salivary SIgA reactivity against human dentin extract in young adults with a history of trauma in the primary dentition. A sample of 78 patients, aged 18 to 25, who had completed an early childhood (0 to 5 years old caries prevention program years earlier at the Universidade Estadual de LondrinaPediatric Clinic, underwent radiographic examination and salivary sampling. Anti-dentin SIgA levels were analyzed by immunoenzymatic assay and Western blotting. Although dental trauma to deciduous teeth had occurred in 34 (43.6% of the patients, no differences in SIgA levels were detected between individuals who had experienced trauma and those who had not (p > 0.05. Multivariate regression analysis showed no association between dental trauma and SIgA levels (p > 0.05. Patients with a history of deciduous trauma presented low levels of anti-dentin antibodies, associated with orthodontic root resorption (p

Oxygen Modulates Human Decidual Natural Killer Cell Surface Receptor Expression and Interactions with Trophoblasts1

Science.gov (United States)

Wallace, Alison E.; Goulwara, Sonu S.; Whitley, Guy S.; Cartwright, Judith E.

2014-01-01

Decidual natural killer (dNK) cells have been shown to both promote and inhibit trophoblast behavior important for decidual remodeling in pregnancy and have a distinct phenotype compared to peripheral blood NK cells. We investigated whether different levels of oxygen tension, mimicking the physiological conditions of the decidua in early pregnancy, altered cell surface receptor expression and activity of dNK cells and their interactions with trophoblast. dNK cells were isolated from terminated first-trimester pregnancies and cultured in oxygen tensions of 3%, 10%, and 21% for 24 h. Cell surface receptor expression was examined by flow cytometry, and the effects of secreted factors in conditioned medium (CM) on the trophoblast cell line SGHPL-4 were assessed in vitro. SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 10% were significantly more invasive (P cells treated with dNK cell CM incubated in oxygen tensions of 3% or 21%. After 24 h, a lower percentage of dNK cells expressed CD56 at 21% oxygen (P cells expressed NKG2D at 10% oxygen (P oxygen tensions, with large patient variation. This study demonstrates dNK cell phenotype and secreted factors are modulated by oxygen tension, which induces changes in trophoblast invasion and endovascular-like differentiation. Alterations in dNK cell surface receptor expression and secreted factors at different oxygen tensions may represent regulation of function within the decidua during the first trimester of pregnancy. PMID:25232021

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

File list: NoD.Utr.05.AllAg.Endometrial_stromal_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: NoD.Utr.50.AllAg.Endometrial_stromal_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: NoD.Utr.10.AllAg.Endometrial_stromal_cells [Chip-atlas[Archive

Lifescience Database Archive (English)

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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 ...

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.

Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk.

Science.gov (United States)

Maxwell, G L; Schildkraut, J M; Calingaert, B; Risinger, J I; Dainty, L; Marchbanks, P A; Berchuck, A; Barrett, J C; Rodriguez, G C

2006-11-01

Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. Subjects included 434 endometrial cancer cases and 2,557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m2 or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m2 did not (OR=1.36, 95% CI=0.39 to 4.70). The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus.

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

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.

Contribution of the RgfD Quorum Sensing Peptide to rgf Regulation and Host Cell Association in Group B Streptococcus

Directory of Open Access Journals (Sweden)

Robert E. Parker

2017-01-01

Full Text Available Streptococcus agalactiae (group B Streptococcus; GBS is a common inhabitant of the genitourinary and/or gastrointestinal tract in up to 40% of healthy adults; however, this opportunistic pathogen is able to breach restrictive host barriers to cause disease and persist in harsh and changing conditions. This study sought to identify a role for quorum sensing, a form of cell to cell communication, in the regulation of the fibrinogen-binding (rgfBDAC two-component system and the ability to associate with decidualized endometrial cells in vitro. To do this, we created a deletion in rgfD, which encodes the putative autoinducing peptide, in a GBS strain belonging to multilocus sequence type (ST-17 and made comparisons to the wild type. Sequence variation in the rgf operon was detected in 40 clinical strains and a non-synonymous single nucleotide polymorphism was detected in rgfD in all of the ST-17 genomes that resulted in a truncation. Using qPCR, expression of rgf operon genes was significantly decreased in the ST-17 ΔrgfD mutant during exponential growth with the biggest difference (3.3-fold occurring at higher cell densities. Association with decidualized endometrial cells was decreased 1.3-fold in the mutant relative to the wild type and rgfC expression was reduced 22-fold in ΔrgfD following exposure to the endometrial cells. Collectively, these data suggest that this putative quorum sensing molecule is important for attachment to human tissues and demonstrate a role for RgfD in GBS pathogenesis through regulation of rgfC.

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

Science.gov (United States)

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

1998-01-01

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

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...

The case against endometrial ablation for treatment of heavy menstrual bleeding.

Science.gov (United States)

Louie, Michelle; Wright, Kelly; Siedhoff, Matthew

2018-04-27

Endometrial ablation is a common treatment for heavy menstrual bleeding, but serious limitations and long-term complications exist. Our purpose is to summarize the use of endometrial ablation devices, potential short-term and long-term complications, cost effectiveness, and quality of life in relation to alternative treatments. There is insufficient evidence to strongly recommend one endometrial ablation device over another. Providers should consider and discuss with their patients, complications including risk of future pregnancy, endometrial cancer, and hysterectomy for continued bleeding or pain. Patient selection is key to reducing postablation pain and failure; patients with a history of tubal ligation and dysmenorrhea should consider alternative treatments. All patients should also be counseled that the levonorgestrel intrauterine device is a cost-effective alternative with higher quality of life and fewer complications. Hysterectomy is definitive treatment with higher quality of life and fewer complications. Although endometrial ablation can offer adequate symptom control for patients who have failed medical therapy, desire uterine preservation, or who are high-risk surgical candidates, patients should be appropriately selected and counseled regarding the potential for treatment failure and long-term complications.

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.

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...

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).

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

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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.

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

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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.

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.

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

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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.

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

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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.

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

Robotic surgery in supermorbidly obese patients with endometrial cancer.

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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

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.

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...

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...

Do evergreen and deciduous trees have different effects on net N mineralization in soil?

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Mueller, Kevin E; Hobbie, Sarah E; Oleksyn, Jacek; Reich, Peter B; Eissenstat, David M

2012-06-01

Evergreen and deciduous plants are widely expected to have different impacts on soil nitrogen (N) availability because of differences in leaf litter chemistry and ensuing effects on net N mineralization (N(min)). We evaluated this hypothesis by compiling published data on net N(min) rates beneath co-occurring stands of evergreen and deciduous trees. The compiled data included 35 sets of co-occurring stands in temperate and boreal forests. Evergreen and deciduous stands did not have consistently divergent effects on net N(min) rates; net N(min) beneath deciduous trees was higher when comparing natural stands (19 contrasts), but equivalent to evergreens in plantations (16 contrasts). We also compared net N(min) rates beneath pairs of co-occurring genera. Most pairs of genera did not differ consistently, i.e., tree species from one genus had higher net N(min) at some sites and lower net N(min) at other sites. Moreover, several common deciduous genera (Acer, Betula, Populus) and deciduous Quercus spp. did not typically have higher net N(min) rates than common evergreen genera (Pinus, Picea). There are several reasons why tree effects on net N(min) are poorly predicted by leaf habit and phylogeny. For example, the amount of N mineralized from decomposing leaves might be less than the amount of N mineralized from organic matter pools that are less affected by leaf litter traits, such as dead roots and soil organic matter. Also, effects of plant traits and plant groups on net N(min) probably depend on site-specific factors such as stand age and soil type.

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

Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women.

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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.

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

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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.

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

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.

Science.gov (United States)

Sugimura-Wakayama, Yukiko; Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Ogata, Kenichi; Sakaguchi, Kohei; Hibi, Hideharu

2015-11-15

Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

VEGF blockade inhibits angiogenesis and reepithelialization of endometrium

OpenAIRE

Fan, Xiujun; Krieg, Sacha; Kuo, Calvin J.; Wiegand, Stanley J.; Rabinovitch, Marlene; Druzin, Maurice L.; Brenner, Robert M.; Giudice, Linda C.; Nayak, Nihar R.

2008-01-01

Despite extensive literature on vascular endothelial growth factor (VEGF) expression and regulation by steroid hormones, the lack of clear understanding of the mechanisms of angiogenesis in the endometrium is a major limitation for use of antiangiogenic therapy targeting endometrial vessels. In the current work, we used the rhesus macaque as a primate model and the decidualized mouse uterus as a murine model to examine angiogenesis during endometrial breakdown and regeneration. We found that ...

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.

Subcutaneous metastasis from endometrial cancer; case report and literature review

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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.

MR staging accuracy for endometrial cancer based on the new FIGO stage

International Nuclear Information System (INIS)

Shin, Kyung Eun; Park, Byung Kwan; Kim, Chan Kyo; Bae, Duk Soo; Song, Sang Yong; Kim, Bohyun

2011-01-01

Background: Magnetic resonance imaging (MRI) has been frequently used to determine a preoperative treatment plan for gynecologic cancers. However, the MR accuracy for staging an endometrial cancer is not satisfactory based on the old FIGO staging system. Purpose: To evaluate MR accuracy for staging endometrial cancer using the new FIGO staging system. Material and Methods: Between January 2005 and May 2009, 199 women underwent surgery due to endometrial cancer. In each patient, an endometrial cancer was staged using MR findings based on the old FIGO staging system and then repeated according to the new FIGO staging system for comparison. Histopathologic findings were used as a standard of reference. Results: The accuracy of MRI in the staging of endometrial carcinoma stage I, II, III, and IV using the old FIGO staging system were 80% (159/199), 89% (178/199), 90% (179/199), and 99% (198/199), respectively, compared to 87% (174/199), 97% (193/199), 90% (179/199), and 99% (198/199), respectively, when using the new FIGO staging criteria. The overall MR accuracy of the old and new staging systems were 51% (101/199) and 81% (161/199), respectively. Conclusion: MRI has become a more useful tool in the preoperative staging of endometrial cancers using the new FIGO staging system compared to the old one with increased accuracy

Mutations of the KRAS oncogene in endometrial hyperplasia and carcinoma.

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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.

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.

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

Studies on changes in the uptake of 3H-estradiol in experimental endometrial carcinoma in rats

International Nuclear Information System (INIS)

Yokoyama, Shiro

1982-01-01

The sensitivity to estrogen of various growth changes of endometrium and endometrial adenocarcinoma induced experimentally in rats was investigated comparatively by autoradiography using 3 H-estradiol. The results indicated that the rate of 3 H-estradiol uptake showed a parallel relation in non-atypical hyperplasia and atypical type I, II, and III, but in atypical type III, which is considered as a precursor of endometrial carcinoma, there was case where the uptake rate resembled that in atypical type I or II rather than that of endometrial carcinoma. In cases of endometrial carcinoma, there were marked changes in the uptake rate and these changes were different from other endometrial changes. This suggests that deviation from estrogen dependence plays an important role in the onset of endometrial carcinoma. (author)

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

The fate of autologous endometrial mesenchymal stromal cells after application in the healthy equine uterus.

Science.gov (United States)

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.

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...

Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens.

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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 polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

Science.gov (United States)

Dominick, Sally; Hickey, Martha; Chin, Jason; Su, H Irene

2015-12-09

Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or

Using gene expression in patients with endometrial intraepithelial neoplasia to assess the risk of cancer

Directory of Open Access Journals (Sweden)

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

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.

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.

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.

Should deciduous teeth be preserved in adult patients? How about stem cells? Is it reasonable to preserve them?

Directory of Open Access Journals (Sweden)

Alberto Consolaro

2016-04-01

Full Text Available Abstract When seeking orthodontic treatment, many adolescents and adult patients present with deciduous teeth. Naturally, deciduous teeth will inevitably undergo exfoliation at the expected time or at a later time. Apoptosis is the biological trigger of root resorption. In adult patients, deciduous teeth should not be preserved, as they promote: infraocclusion, traumatic occlusion, occlusal trauma, diastemata and size as well as morphology discrepancy malocclusion. Orthodontic movement speeds root resorption up, and so do restoring or recontouring deciduous teeth in order to establish esthetics and function. Deciduous teeth cells are dying as a result of apoptosis, and their regeneration potential, which allows them to act as stem cells, is limited. On the contrary, adult teeth cells have a greater proliferative potential. All kinds of stem cell therapies are laboratory investigative non authorized trials.

Potential contribution of the uterine microbiome in the development of endometrial cancer

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Marina R. S. Walther-António

2016-11-01

Full Text Available Abstract Background Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer. Methods We undertook a study of the microbiome in samples taken from different locations along the female reproductive tract in patients with endometrial cancer (n = 17, patients with endometrial hyperplasia (endometrial cancer precursor, n = 4, and patients afflicted with benign uterine conditions (n = 10. Vaginal, cervical, Fallopian, ovarian, peritoneal, and urine samples were collected aseptically both in the operating room and the pathology laboratory. DNA extraction was followed by amplification and high-throughput next generation sequencing (MiSeq of the 16S rDNA V3-V5 region to identify the microbiota present. Microbiota data were summarized using both α-diversity to reflect species richness and evenness within bacterial populations and β-diversity to reflect the shared diversity between bacterial populations. Statistical significance was determined through the use of multiple testing, including the generalized mixed-effects model. Results The microbiome sequencing (16S rDNA V3-V5 region revealed that the microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries are significantly correlated (p 4.5. Conclusions Our results suggest that the detection of A. vaginae and the identified Porphyromonas sp. in the gynecologic tract combined with a high vaginal pH is statistically associated with the presence of endometrial cancer. Given the documented association of the identified microorganisms with other pathologies, these findings raise the possibility of a microbiome role in the manifestation, etiology, or progression of endometrial cancer that

Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.

Science.gov (United States)

Wong, L F A; Wahab, N A; Gleeson, N

2014-01-01

There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery. This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period. Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group. Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.

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.

Contribution of spiral artery blood flow changes assessed by transvaginal color Doppler sonography for predicting endometrial pathologies

Directory of Open Access Journals (Sweden)

Suna Kabil Kucur

2013-01-01

Full Text Available ive: To investigate the diagnostic value of blood flow measurements in spiral artery by transvaginal color Doppler sonography (CDS in predicting endometrial pathologies.Methods: Ninety-seven patients presenting with abnormal uterine bleeding and requiring endometrial assessment were included in this prospective observational study. Endometrial thickness, structure and echogenicity were recorded. Pulsatility index (PI and resistive index (RI of the spiral artery were measured by transvaginal CDS. Endometrial sampling was performed for all subjects. Sonographic and hystopathologic findings were compared.Results: The histopathological diagnoses were as follows; 39 cases (40.2% endometrial polyp, 9 cases (9.3% endometrial hyperplasia, 10 cases (10.3 submucous myoma, 7 cases (7.2% endometrium cancer, and 32 cases (33% nonspecific findings. The spiral artery PI in endometrium cancer group was highly significantly lower than other groups (p<0.01. The spiral artery RI was also significantly lower in the patients with malignant histology (p<0.05. Conclusion: Endometrial pathologies are associated significantly with endometrial spiral artery Doppler changes.Key words: Spiral artery, Doppler ultrasonography, endometrium

Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome.

Science.gov (United States)

Nebgen, Denise R; Lu, Karen H; Rimes, Sue; Keeler, Elizabeth; Broaddus, Russell; Munsell, Mark F; Lynch, Patrick M

2014-10-01

Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1-2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1-2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

The Endocannabinoid System in the Postimplantation Period: A Role during Decidualization and Placentation

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B. M. Fonseca

2013-01-01

Full Text Available Although the detrimental effects of cannabis consumption during gestation are known for years, the vast majority of studies established a link between cannabis consumption and foetal development. The complex maternal-foetal interrelationships within the placental bed are essential for normal pregnancy, and decidua definitively contributes to the success of this process. Nevertheless, the molecular signalling network that coordinates strategies for successful decidualization and placentation are not well understood. The discovery of the endocannabinoid system highlighted new signalling mediators in various physiological processes, including reproduction. It is known that endocannabinoids present regulatory functions during blastocyst development, oviductal transport, and implantation. In addition, all the endocannabinoid machinery was found to be expressed in decidual and placental tissues. Additionally, endocannabinoid’s plasmatic levels were found to fluctuate during normal gestation and to induce decidual cell death and disturb normal placental development. Moreover, aberrant endocannabinoid signalling during the period of placental development has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the endocannabinoid system in these critical processes is explored and discussed.

Deciduous forest responses to temperature, precipitation, and drought imply complex climate change impacts.

Science.gov (United States)

Xie, Yingying; Wang, Xiaojing; Silander, John A

2015-11-03

Changes in spring and autumn phenology of temperate plants in recent decades have become iconic bio-indicators of rapid climate change. These changes have substantial ecological and economic impacts. However, autumn phenology remains surprisingly little studied. Although the effects of unfavorable environmental conditions (e.g., frost, heat, wetness, and drought) on autumn phenology have been observed for over 60 y, how these factors interact to influence autumn phenological events remain poorly understood. Using remotely sensed phenology data from 2001 to 2012, this study identified and quantified significant effects of a suite of environmental factors on the timing of fall dormancy of deciduous forest communities in New England, United States. Cold, frost, and wet conditions, and high heat-stress tended to induce earlier dormancy of deciduous forests, whereas moderate heat- and drought-stress delayed dormancy. Deciduous forests in two eco-regions showed contrasting, nonlinear responses to variation in these explanatory factors. Based on future climate projection over two periods (2041-2050 and 2090-2099), later dormancy dates were predicted in northern areas. However, in coastal areas earlier dormancy dates were predicted. Our models suggest that besides warming in climate change, changes in frost and moisture conditions as well as extreme weather events (e.g., drought- and heat-stress, and flooding), should also be considered in future predictions of autumn phenology in temperate deciduous forests. This study improves our understanding of how multiple environmental variables interact to affect autumn phenology in temperate deciduous forest ecosystems, and points the way to building more mechanistic and predictive models.

Reconstructing the life-time lead exposure in children using dentine in deciduous teeth

Energy Technology Data Exchange (ETDEWEB)

Shepherd, Thomas J., E-mail: shepherdtj@aol.com [School of Earth and Environment, University of Leeds, Leeds LS2 9JT (United Kingdom); Dirks, Wendy [Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Newcastle upon Tyne NE2 4BW (United Kingdom); Manmee, Charuwan; Hodgson, Susan [Institute of Health and Society, Newcastle University, Newcastle upon Tyne NE2 4AX (United Kingdom); Banks, David A. [School of Earth and Environment, University of Leeds, Leeds LS2 9JT (United Kingdom); Averley, Paul [Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Newcastle upon Tyne NE2 4BW (United Kingdom); Queensway Dental Practice, 170 Queensway, Billingham, Teesside TS23 2NT (United Kingdom); Pless-Mulloli, Tanja [Institute of Health and Society, Newcastle University, Newcastle upon Tyne NE2 4AX (United Kingdom); Newcastle Institute for Research on Sustainability, Newcastle University, Newcastle upon Tyne NE1 7RU (United Kingdom)

2012-05-15

Data are presented to demonstrate that the circumpulpal dentine of deciduous teeth can be used to reconstruct a detailed record of childhood exposure to lead. By combining high spatial resolution laser ablation ICP-MS with dental histology, information was acquired on the concentration of lead in dentine from in utero to several years after birth, using a true time template of dentine growth. Time corrected lead analyses for pairs of deciduous molars confirmed that between-tooth variation for the same child was negligible and that meaningful exposure histories can be obtained from a single, multi-point ablation transect on longitudinal sections of individual teeth. For a laser beam of 100 {mu}m diameter, the lead signal for each ablation point represented a time span of 42 days. Simultaneous analyses for Sr, Zn and Mg suggest that the incorporation of Pb into dentine (carbonated apatite) is most likely controlled by nanocrystal growth mechanisms. The study also highlights the importance of discriminating between primary and secondary dentine and the dangers of translating lead analyses into blood lead estimates without determining the age or duration of dentine sampled. Further work is in progress to validate deciduous teeth as blood lead biomarkers. - Highlights: Black-Right-Pointing-Pointer Reconstruction of childhood exposure history to Pb using deciduous tooth dentine. Black-Right-Pointing-Pointer Pb analyses acquired for dentine growth increments of 42 days. Black-Right-Pointing-Pointer Highly correlated Pb concentration profiles for pairs of deciduous molars. Black-Right-Pointing-Pointer Data for Sr, Zn and Mg provide a model for the incorporation of Pb into dentine.

Reconstructing the life-time lead exposure in children using dentine in deciduous teeth

International Nuclear Information System (INIS)

Shepherd, Thomas J.; Dirks, Wendy; Manmee, Charuwan; Hodgson, Susan; Banks, David A.; Averley, Paul; Pless-Mulloli, Tanja

2012-01-01

Data are presented to demonstrate that the circumpulpal dentine of deciduous teeth can be used to reconstruct a detailed record of childhood exposure to lead. By combining high spatial resolution laser ablation ICP-MS with dental histology, information was acquired on the concentration of lead in dentine from in utero to several years after birth, using a true time template of dentine growth. Time corrected lead analyses for pairs of deciduous molars confirmed that between-tooth variation for the same child was negligible and that meaningful exposure histories can be obtained from a single, multi-point ablation transect on longitudinal sections of individual teeth. For a laser beam of 100 μm diameter, the lead signal for each ablation point represented a time span of 42 days. Simultaneous analyses for Sr, Zn and Mg suggest that the incorporation of Pb into dentine (carbonated apatite) is most likely controlled by nanocrystal growth mechanisms. The study also highlights the importance of discriminating between primary and secondary dentine and the dangers of translating lead analyses into blood lead estimates without determining the age or duration of dentine sampled. Further work is in progress to validate deciduous teeth as blood lead biomarkers. - Highlights: ► Reconstruction of childhood exposure history to Pb using deciduous tooth dentine. ► Pb analyses acquired for dentine growth increments of 42 days. ► Highly correlated Pb concentration profiles for pairs of deciduous molars. ► Data for Sr, Zn and Mg provide a model for the incorporation of Pb into dentine.

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

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

Effect of demographic factors on brachytherapy treatment results in patients with endometrial cancer 1995-2010.

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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.

MicroRNA-424 suppresses estradiol-induced cell proliferation via targeting GPER in endometrial cancer cells.

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Zhang, H; Wang, X; Chen, Z; Wang, W

2015-11-30

Endometrial carcinoma (EC) is the most common gynecologic malignancy with increasing morbidity in recent years. MicroRNAs (miRNAs), a type of non-coding RNA, have been proven to be critical in the process of tumorigenesis. miR-424 has been reported to play a protective role in various type of cancer including endometrial carcinoma. It has been reported that high levels of estrogen increase morbidity of EC by promoting cell growth ability. The current research was designed to delineate the mechanism of miR-424 in regulating E2 (17β-estradiol)-induced cell proliferation in endometrial cancer. In this study, we confirmed that cell proliferation is increased significantly in E2-treated endometrial cancer cell lines. Moreover, miR-424 overexpression dramatically decreased E2-induced cell proliferation, indicating a pivotal role in endometrial cancer cell growth. In addition, the results suggest that miR-424 up-regulation inactivated the PI3K/AKT signaling, which was mediated by G-protein-coupled estrogen receptor-1 (GPER) in endometrial cancer. Furthermore, the luciferase report confirmed the targeting reaction between miR-424 and GPER. After transfection with the GPER overexpression vector into E2-induced endometrial cancer cells, we found that GPER significantly attenuated the inhibition effect of miR-424 in E2-induced cell growth in EC. Taken together, our study suggests that increased miR-424 suppresses E2-induced cell growth, and providing a potential therapeutic target for estrogen-associated endometrial carcinoma.

Maternal obesogenic diet induces endometrial hyperplasia, an early hallmark of endometrial cancer, in a diethylstilbestrol mouse model.

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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.

Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.

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Maoyong Fu

Full Text Available Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2, a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.

Effect of Radiofrequency Endometrial Ablation on Dysmenorrhea.

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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.

Immunomodulatory Role of Stem Cell from Human Exfoliated Deciduous Teeth on Periodontal Regeneration.

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Gao, Xianling; Shen, Zongshan; Guan, Meiliang; Huang, Qiting; Chen, Lingling; Qin, Wei; Ge, Xiaohu; Chen, Haijia; Xiao, Yin; Lin, Zhengmei

2018-03-20

Periodontitis is initiated by the infection of periodontal bacteria and subsequent tissue inflammation due to immunoreaction, eventually leading to periodontal apparatus loss. Stem cells from human exfoliated deciduous teeth (SHEDs) have exhibited beneficial characteristics in dental tissue regeneration. However, the immunomodulatory functions of SHEDs have not been elucidated in the context of periodontitis treatment. In this study, we investigated the potential immunomodulatory effects of SHEDs on experimental periodontitis and demonstrated that multi-dose delivery of SHEDs led to periodontal tissue regeneration. SHEDs and monocytes/macrophages were cocultured in transwell systems and SHEDs were found to be capable of promoting monocyte/macrophages conversion to CD206+ M2-like phenotype. Bioluminescence imaging (BLI) was employed to assess the survival and distribution of SHEDs after delivery in periodontal tissues in an induced periodontitis model, and BLI revealed that SHEDs survived for approximately 7 days in periodontal tissues with little tissue diffusion. Then, multi-dose SHEDs delivery was applied to treat periodontitis at 7-day intervals. Results showed that muti-dose SHEDs altered the cytokine expression profile in gingival crevicular fluid, reduced gum bleeding, increased new attachment of periodontal ligament and decreased osteoclast differentiation. Micro-computed tomography analysis showed SHEDs administration significantly increased periodontal regeneration and alveolar bone volume, and decreased distance of cementoenamel junction to alveolar bone crest (CEJ-ABC). Furthermore, an increase in the number of CD206+ M2 macrophages was observed in periodontal tissues following the delivery of SHEDs, which aligned well with the promoted conversion to CD206+ M2-like cells from monocytes/macrophages in vitro after stimulation by SHEDs. This study demonstrated in a rat periodontitis model that local delivery of SHEDs attributed to the induction of M2

Modified distal shoe appliance for premature loss of multiple deciduous molars: a case report.

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Bhat, Prasanna Kumar; K, Navin H; Idris, Mohammed; Christopher, Pradeep; Rai, Niharika

2014-08-01

Preservation of the primary dentition until the normal time of exfoliation is one of the most important factor involved in preventive and interceptive dentistry. The premature loss of second primary molar before the eruption of permanent first molar can create a significant arch space/tooth size discrepancy. Distal shoe space maintainer is a valuable part of the Paediatric Dentist's armamentarium in those cases where the second primary molar is prematurely lost and it helps to guide the first permanent molar into place. Conventional design poses various limitations in cases of premature loss of multiple deciduous molars. Thus, it is required to modify the conventional designs according to the needs of the patient. This case report describes an innovative modification of distal shoe appliance in cases of premature loss of multiple deciduous molars. In the present case, modification of distal shoe space maintainer was advocated because of inadequate abutments caused due to multiple loss of deciduous molars. Bilateral design of distal shoe was planned for unilateral loss of deciduous molars.

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...

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...

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...

BMP4 Expression Following Stem Cells from Human Exfoliated Deciduous and Carbonate Apatite Transplantation on Rattus norvegicus

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Tania Saskianti

2018-04-01

Full Text Available Background: Alveolar bone defects in children still have a high incidence. Conventional bone graft technique that has been used as a defect therapy is still not effective, so new techniques with tissue engineering approach are needed. Bone Morphogenetic Protein 4 (BMP4 as one of the indicators of osteogenic differentiation has not been widely studied, especially in the transplantation with combination of Stem Cells from Human Exfoliated Deciduous (SHED and carbonate apatite. Aim and Objectives: This research aimed to determine the expression of BMP4 after SHED and carbonate apatite transplantation on Rattus norvegicus. Material and Methods: The combinations of SHED and carbonate apatite were transplanted on alveolar bone defects of 4 rats (Rattus norvegicus as the treatment groups and another 4 rats were transplanted with carbonate apatite as the control groups. After 21 days, staining with Hematoxylin Eosin (HE and Immunohistochemistry (IHC BMP4 was performed. Results: BMP4 expression in the treatment groups was significantly higher when compared to the control groups. Discussion: Carbonate apatite has low crystallization rate and high osteoconductivity that produce more osteoblasts and increased BMP4 expression. Conclusion: The transplantation of SHED and carbonate apatite increased BMP4 expression as an indicator of osteogenic differentiation in rats.

Hysteroscopic endometrial resection: efficacy and factors for failure

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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.

Endometrial Carcinoma in a 26-Year-Old Patient with Bardet-Biedl Syndrome

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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.

Flammulated Owls (Otus flammeolus) breeding in deciduous forests

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Carl D. Marti

1997-01-01

The first studies of nesting Flammulated Owls (Otus flammeolus) established the idea that the species needs ponderosa pine (Pinus ponderosa) forests for breeding. In northern Utah, Flammulated Owls nested in montane deciduous forests dominated by quaking aspen (Populus tremuloides). No pines were present but...

Prevalence and characteristics of endometrial polyps in patients with abnormal uterine bleeding

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Đorđević Biljana

2008-01-01

Full Text Available Background/Aim. The prevalence of endometrial polyps (EPs in the general female population is about 24%. Abnormal uterine bleeding is frequently the presenting symptom of EPs. The aim of this study was to determine the prevalence and characteristics of EPs in patients with abnormal uterine bleeding. Methods. The prevalence and characteristics of EPs were investigated in 961 patients with abnormal uterine bleeding who underwent dilatation and curettage between January and December 2006. Regarding histopathological features of EPs (presence of atypical hyperplasia or endometrial carcinoma, patients were divided into two groups: group A - patients who had EPs and EPs with hyperplasia without atypia (n = 204 and group B - patients who had EPs with atypical hyperplasia and EPs with carcinoma (n = 7. Results. In 211 (21.94% patients EPs were found with abnormal uterine bleeding. Histopathologically, there were 175 (82.94% EPs, 29 (13.74% EPs with hyperplasia without atypia, 5 (2.37% EPs with atypical hyperplasia, and 2 (0.95% EPs with endometrial carcinoma. Contrary to the patients with EPs and EPs with hyperplasia without atypia (group A, patients who had EPs with atypical hyperplasia and EPs with carcinoma (group B were older (p < 0.05, and more commonly postmenopausal (p < 0.05 and with hypertension (p < 0.05, all of statistical significance. Conclusion. The prevalence of endometrial polyps in patients with abnormal uterine bleeding according to our data was 21.95%. Atypical hyperplasia and endometrial carcinoma were rarely confined to a polyp. Older age, postmenopausal period and hypertension may increase the risk of premalignant and malignant changes in endometrial polyps.

Implantation in assisted reproduction: a look at endometrial receptivity.

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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.

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.

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

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Bohîlțea, R E; Ancăr, V; Cirstoiu, M M; Rădoi, V; Bohîlțea, L C; Furtunescu, F

2015-01-01

Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania, reaching in 2013 the average value of 8.06/ 100,000 women, and 15.97/ 100,000 women within the highest risk age range, having in recent years an increasing trend, being higher in urban than in rural population. Annually, approximately 800 new cases are registered in our country. The estimated lifetime risk of a woman to develop endometrial cancer is of about 1,03%. Based on an abnormal uterine bleeding, 35% of the endometrial cancers are diagnosed in an advanced stage of the disease, with significantly diminished lifetime expectancy. Drafting a national program for the early diagnosis of endometrial cancer. We proposed a standardization of the diagnostic steps and focused on 4 key elements for the early diagnosis of endometrial cancer: investigation of abnormal uterine bleeding occurring in pre/ post-menopausal women, investigating features/ anomalies of cervical cytology examination, diagnosis, treatment and proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR = International Normalized Ratio, MSI = Microsatellites instability, MSI

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

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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.

Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy.

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Della Badia, Carl; Karini, Homa

2010-01-01

Endometrial stromal sarcoma is a rare uterine cancer with no reliable method for preoperative diagnosis. A 30-year-old parous woman underwent laparoscopic supracervical hysterectomy because of a leiomyoma. The uterus was removed from the abdominal cavity with an electric morcellator with a spinning blade. The pathology report revealed low-grade endometrial stromal sarcoma. Two months after the initial surgery, a second laparoscopic procedure was performed. The final pathology report confirmed low-grade endometrial stromal sarcoma involving the ovary, fallopian tube, and ovarian artery. It was concluded that morcellation of leiomyomas at laparoscopic supracervical hysterectomy may potentially increase metastasis if the tumor is a sarcoma. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Estrogen receptor alpha gene polymorphism and endometrial cancer risk – a case-control study

International Nuclear Information System (INIS)

Wedrén, Sara; Stiger, Fredrik; Persson, Ingemar; Baron, John A; Weiderpass, Elisabete; Lovmar, Lovisa; Humphreys, Keith; Magnusson, Cecilia; Melhus, Håkan; Syvänen, Ann-Christine; Kindmark, Andreas; Landegren, Ulf; Fermér, Maria Lagerström

2008-01-01

Estrogen is an established endometrial carcinogen. One of the most important mediators of estrogenic action is the estrogen receptor alpha. We have investigated whether polymorphic variation in the estrogen receptor alpha gene (ESR1) is associated with endometrial cancer risk. In 702 cases with invasive endometrial cancer and 1563 controls, we genotyped five markers in ESR1 and used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI). We found an association between rs2234670, rs2234693, as well as rs9340799, markers in strong linkage disequilibrium (LD), and endometrial cancer risk. The association with rs9340799 was the strongest, OR 0.75 (CI 0.60–0.93) for heterozygous and OR 0.53 (CI 0.37–0.77) for homozygous rare compared to those homozygous for the most common allele. Haplotype models did not fit better to the data than single marker models. We found that intronic variation in ESR1 was associated with endometrial cancer risk

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.

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.

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

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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.

Management of unerupted maxillary deciduous central incisor: a case report.

Science.gov (United States)

Shakra, Karam Abu

2014-01-01

Failure of eruption of primary teeth can be considered rare, especially in maxillary anterior teeth. The problem can be either mechanical obstruction of eruption or a failure of the eruption mechanism. This case report presents failure of eruption of the maxillary right deciduous central incisor in a 4-year-old girl. The unerupted primary tooth was removed surgically. The histological finding revealed fibroma with reactive giant cells. Periodic follow-up visits were advised to monitor the developing dentition and to ensure enough space for the permanent incisor. How to cite this article: Shakra KA. Management of Unerupted Maxillary Deciduous Central Incisor: A Case Report. Int J Clin Pediatr Dent 2014;7(1):58-60.

Application of micro-PIXE analysis to investigate trace elements in deciduous teeth enamel

International Nuclear Information System (INIS)

Igari, K.; Takahashi, A.; Ando, H.

2010-01-01

The early life environment has widespread consequences for later health and disease. To prevent the disease in later life, the assessment of fetal environment is very important. In Japan, birthweight has fallen rapidly during recent two decades. The reduction of birthweight represents reduced fetal nutrition. Deciduous tooth enamel contains pre- and postnatal enamel and its chemical composition reflects the status of metabolism of trace elements during formation period. Deciduous tooth enamel is considered to be a suitable indicator of trace elements exposure in utero. We applied micro-PIXE analysis to investigate the trace elemental content in deciduous tooth enamel. Two deciduous canines from one healthy Japanese boy were used for this study. The enamel section including pre- and postnatal enamel was prepared for micro-PIXE analysis. Five trace elements (Na, Mg, Cl, Zn, and Sr) were detected in the scanning area of tooth. The distribution profiles of 5 elements were obtained as X-ray maps. The distribution profiles of zinc and chlorine were specific, and showed higher concentration in surface enamel. No elements showed different profiles of X-ray maps between pre- and postnatal enamel in this sample. The results of this study suggested that micro-PIXE analysis would be able to estimate the trace elements in prenatal and postnatal enamel, respectively. (author)

Emerging molecular-targeted therapies—the challenging case of endometrial cancer

Directory of Open Access Journals (Sweden)

Ines Vasconcelos

2015-10-01

Full Text Available Endometrial cancer newly affects an estimated 54,870 women in the United States, being responsible for an estimated 10,170 deaths in 2015. It has demonstrated to harbor a complex carcinogenesis process, with limited treatment options for advanced or persistent disease. Identification and targeting of genetic alterations that lead to progressive disease and therapy resistance is not only challenging, but also often does not correlate with a clinical benefit. Targeted maintenance therapies in endometrial cancer have been largely disappointing. Nonetheless, targeted personalized treatment should be the main goal of treatment of advanced disease in the future. Due to the high variety of drugs being tested in early clinical trials, it is hard to keep pace with the latest developments and ongoing trials. This review aims to summarize the latest published and ongoing trials on targeted therapies in endometrial cancer.