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Sample records for endometrial matrix remodeling

  1. Endometrial stromal cell attachment and matrix homeostasis in abdominal wall endometriomas.

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    Itoh, Hiroko; Mogami, Haruta; Bou Nemer, Laurice; Word, Larry; Rogers, David; Miller, Rodney; Word, R Ann

    2018-02-01

    How does progesterone alter matrix remodeling in abdominal wall endometriomas compared with normal endometrium? Progesterone may prevent attachment of endometrial cells to the abdominal wall, but does not ameliorate abnormal stromal cell responses of abdominal wall endometriomas. Menstruation is a tightly orchestrated physiologic event in which steroid hormones and inflammatory cells cooperatively initiate shedding of the endometrium. Abdominal wall endometriomas represent a unique form of endometriosis in which endometrial cells inoculate fascia or dermis at the time of obstetrical or gynecologic surgery. Invasion of endometrium into ectopic sites requires matrix metalloproteinases (MMPs) for tissue remodeling but endometrium is not shed externally. Observational study in 14 cases and 19 controls. Tissues and stromal cells isolated from 14 abdominal wall endometriomas were compared with 19 normal cycling endometrium using immunohistochemistry, quantitative PCR, gelatin zymography and cell attachment assays. P values cell preps to provide scientific rigor to the conclusions. The results indicate that MMP2 and MMP9 are not increased by TGFβ1 in endometrioma stromal cells. Although progesterone prevents attachment of endometrioma cells to matrix components of the abdominal wall, it does not ameliorate these abnormal stromal cell responses to TGFβ1. N/A. Endometriomas were collected from women identified pre-operatively. Not all endometriomas were collected. Stromal cells from normal endometrium were from different patients, not women undergoing endometrioma resection. This work provides insight into the mechanisms by which progesterone may prevent abdominal wall endometriomas but, once established, are refractory to progesterone treatment. Tissue acquisition was supported by NIH P01HD087150. Authors have no competing interests. © The Author(s) 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All

  2. Matrix remodeling between cells and cellular interactions with collagen bundle

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    Kim, Jihan; Sun, Bo

    When cells are surrounded by complex environment, they continuously probe and interact with it by applying cellular traction forces. As cells apply traction forces, they can sense rigidity of their local environment and remodel the matrix microstructure simultaneously. Previous study shows that single human carcinoma cell (MDA-MB-231) remodeled its surrounding extracellular matrix (ECM) and the matrix remodeling was reversible. In this study we examined the matrix microstructure between cells and cellular interaction between them using quantitative confocal microscopy. The result shows that the matrix microstructure is the most significantly remodeled between cells consisting of aligned, and densified collagen fibers (collagen bundle)., the result shows that collagen bundle is irreversible and significantly change micromechanics of ECM around the bundle. We further examined cellular interaction with collagen bundle by analyzing dynamics of actin and talin formation along with the direction of bundle. Lastly, we analyzed dynamics of cellular protrusion and migrating direction of cells along the bundle.

  3. A Collagen-based Scaffold Delivering Exogenous MicroRNA-29B to Modulate Extracellular Matrix Remodeling

    OpenAIRE

    Monaghan, Michael; Browne, Shane; Schenke-Layland, Katja; Pandit, Abhay

    2014-01-01

    Directing appropriate extracellular matrix remodeling is a key aim of regenerative medicine strategies. Thus, antifibrotic interfering RNA (RNAi) therapy with exogenous microRNA (miR)-29B was proposed as a method to modulate extracellular matrix remodeling following cutaneous injury. It was hypothesized that delivery of miR-29B from a collagen scaffold will efficiently modulate the extracellular matrix remodeling response and reduce maladaptive remodeling such as aggressive deposition of coll...

  4. The role of extracellular matrix metalloproteinase inducer (EMMPRIN) in the regulation of bovine endometrial cell functions.

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    Mishra, Birendra; Kizaki, Keiichiro; Sato, Takashi; Ito, Akira; Hashizume, Kazuyoshi

    2012-06-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell surface glycoprotein that stimulates the production of several matrix metalloproteinases (MMPs) for tissue remodeling. Previously, we detected EMMPRIN in the bovine endometrium, and it is mainly expressed in the luminal and glandular epithelium whereas MMPs are expressed in the underlying stroma. From this expression pattern, we hypothesized that EMMPRIN may regulate stromal MMPs in endometrial cell functions. To test this hypothesis, a coculture of epithelial and stromal cells was performed using a transwell system. In the coculture, epithelial cells were cultured on the insert membrane and stromal cell on the surface of well plates. Expression of stromal MMP-2 and MMP-14 was significantly higher in coculture with epithelial cell. Further, with the addition of anti-EMMPRIN antibody into the epithelial cell compartment, the expression of stromal EMMPRIN and MMP-2 and MMP-14 was decreased. To identify the active site of EMMPRIN for the augmentation of MMPs, EMMPRIN synthetic peptides that correspond to the extracellular loop domain-I (EM1, EM2, EM3, and EM4) were added into the epithelial cell compartment, and only EM2 at a higher dose interfered with EMMPRIN-mediated expression of MMP-14. Next, we examined the effects of progesterone and/or estrogen on the expression of EMMPRIN, MMP-2, and MMP-14. Progesterone (300 nM) significantly stimulated the expression of EMMPRIN but had no effects on any of the MMPs. These results suggest that EMMPRIN derived from epithelial cells regulates MMPs in the endometrium under progesterone-rich conditions and may thereby modulate bovine endometrial cell functions during gestation.

  5. Biglycan fragmentation in pathologies associated with extracellular matrix remodeling by matrix metalloproteinases

    DEFF Research Database (Denmark)

    Genovese, Federica; Barascuk, Natasha; Larsen, Lise Skakkebæk

    2013-01-01

    The proteoglycan biglycan (BGN) is involved in collagen fibril assembly and its fragmentation is likely to be associated with collagen turnover during the pathogenesis of diseases which involve dysregulated extracellular matrix remodeling (ECMR), such as rheumatoid arthritis (RA) and liver fibrosis...

  6. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

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    Chiu, Chi-Li; Digman, Michelle A.; Gratton, Enrico

    2013-01-01

    Extracellular matrix (ECM) remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG) images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7), which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3). We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments. PMID:23935614

  7. 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.

  8. The emerging role of skeletal muscle extracellular matrix remodelling in obesity and exercise.

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    Martinez-Huenchullan, S; McLennan, S V; Verhoeven, A; Twigg, S M; Tam, C S

    2017-07-01

    Skeletal muscle extracellular matrix remodelling has been proposed as a new feature associated with obesity and metabolic dysfunction. Exercise training improves muscle function in obesity, which may be mediated by regulatory effects on the muscle extracellular matrix. This review examined available literature on skeletal muscle extracellular matrix remodelling during obesity and the effects of exercise. A non-systematic literature review was performed on PubMed of publications from 1970 to 2015. A total of 37 studies from humans and animals were retained. Studies reported overall increases in gene and protein expression of different types of collagen, growth factors and enzymatic regulators of the skeletal muscle extracellular matrix in obesity. Only two studies investigated the effects of exercise on skeletal muscle extracellular matrix during obesity, with both suggesting a regulatory effect of exercise. The effects of exercise on muscle extracellular matrix seem to be influenced by the duration and type of exercise training with variable effects from a single session compared with a longer duration of exercise. More studies are needed to elucidate the mechanisms behind skeletal muscle extracellular matrix remodelling during obesity and the effects of exercise. © 2017 World Obesity Federation.

  9. A collagen-based scaffold delivering exogenous microrna-29B to modulate extracellular matrix remodeling.

    Science.gov (United States)

    Monaghan, Michael; Browne, Shane; Schenke-Layland, Katja; Pandit, Abhay

    2014-04-01

    Directing appropriate extracellular matrix remodeling is a key aim of regenerative medicine strategies. Thus, antifibrotic interfering RNA (RNAi) therapy with exogenous microRNA (miR)-29B was proposed as a method to modulate extracellular matrix remodeling following cutaneous injury. It was hypothesized that delivery of miR-29B from a collagen scaffold will efficiently modulate the extracellular matrix remodeling response and reduce maladaptive remodeling such as aggressive deposition of collagen type I after injury. The release of RNA from the scaffold was assessed and its ability to silence collagen type I and collagen type III expression was evaluated in vitro. When primary fibroblasts were cultured with scaffolds doped with miR-29B, reduced levels of collagen type I and collagen type III mRNA expression were observed for up to 2 weeks of culture. When the scaffolds were applied to full thickness wounds in vivo, reduced wound contraction, improved collagen type III/I ratios and a significantly higher matrix metalloproteinase (MMP)-8: tissue inhibitor of metalloproteinase (TIMP)-1 ratio were detected when the scaffolds were functionalized with miR-29B. Furthermore, these effects were significantly influenced by the dose of miR-29B in the collagen scaffold (0.5 versus 5 μg). This study shows a potential of combining exogenous miRs with collagen scaffolds to improve extracellular matrix remodeling following injury.

  10. Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.

    Science.gov (United States)

    Horn, Margaux A; Trafford, Andrew W

    2016-04-01

    Cardiovascular disease is a leading cause of death worldwide and there is a pressing need for new therapeutic strategies to treat such conditions. The risk of developing cardiovascular disease increases dramatically with age, yet the majority of experimental research is executed using young animals. The cardiac extracellular matrix (ECM), consisting predominantly of fibrillar collagen, preserves myocardial integrity, provides a means of force transmission and supports myocyte geometry. Disruptions to the finely balanced control of collagen synthesis, post-synthetic deposition, post-translational modification and degradation may have detrimental effects on myocardial functionality. It is now well established that the aged heart is characterized by fibrotic remodelling, but the mechanisms responsible for this are incompletely understood. Furthermore, studies using aged animal models suggest that interstitial remodelling with disease may be age-dependent. Thus with the identification of new therapeutic strategies targeting fibrotic remodelling, it may be necessary to consider age-dependent mechanisms. In this review, we discuss remodelling of the cardiac collagen matrix as a function of age, whilst highlighting potential novel mediators of age-dependent fibrotic pathways. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts

    DEFF Research Database (Denmark)

    Perentes, Jean Y; McKee, Trevor D; Ley, Carsten D

    2009-01-01

    Here we integrated multiphoton laser scanning microscopy and the registration of second harmonic generation images of collagen fibers to overcome difficulties in tracking stromal cell-matrix interactions for several days in live mice. We show that the matrix-modifying hormone relaxin increased...... tumor-associated fibroblast (TAF) interaction with collagen fibers by stimulating beta1-integrin activity, which is necessary for fiber remodeling by matrix metalloproteinases....

  12. Matrix Remodeling in Pulmonary Fibrosis and Emphysema

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    O’Reilly, Philip; Antony, Veena B.; Gaggar, Amit

    2016-01-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

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

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    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.

  14. Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

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    Qishan Chen

    2013-01-01

    Full Text Available Abnormal angiogenesis and vascular remodeling contribute to pathogenesis of a number of disorders such as tumor, arthritis, atherosclerosis, restenosis, hypertension, and neurodegeneration. During angiogenesis and vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs, and vascular smooth muscle cells (VSMCs and its interaction with extracellular matrix (ECM play a critical role in the processes. Matrix metalloproteinases (MMPs, well-known inflammatory mediators are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and pathological processes. MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated, MMPs degrade ECM proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of MMPs shows therapeutic potential.

  15. Maintenance of neural progenitor cell stemness in 3D hydrogels requires matrix remodelling

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    Madl, Christopher M.; Lesavage, Bauer L.; Dewi, Ruby E.; Dinh, Cong B.; Stowers, Ryan S.; Khariton, Margarita; Lampe, Kyle J.; Nguyen, Duong; Chaudhuri, Ovijit; Enejder, Annika; Heilshorn, Sarah C.

    2017-12-01

    Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from ~0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodelling to facilitate cadherin-mediated cell-cell contact and promote β-catenin signalling. In two additional hydrogel systems, permitting NPC-mediated matrix remodelling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodelling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D.

  16. Spatio-Temporal Mapping of Matrix Remodeling and Evidence of in-situ Elastogenesis in Experimental Abdominal Aortic Aneurysms

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    Deb, Partha Pratim; Ramamurthi, Anand

    2014-01-01

    Spatio-temporal changes in the extracellular matrix (ECM) were studied within abdominal aortic aneurysms (AAA) generated in rats via elastase-infusion. At 7, 14, and 21 days post-induction, AAA tissues were divided into proximal, mid and distal regions based on their location relative to the renal arteries and region of maximal aortic diameter. Wall thicknesses differed significantly between the AAA spatial regions, initially increasing due to positive matrix remodeling, and then decreasing due to wall thinning and compaction of matrix as the disease progressed. Histological images analyzed using custom segmentation tools indicated significant differences in ECM composition and structure, versus healthy tissue and in the extent and nature of matrix remodeling, between the AAA spatial regions. Histology and immunofluorescence (IF) labeling provided evidence of neointimal AAA remodeling characterized by presence of elastin-containing fibers. This remodeling was effected by smooth muscle alpha actin-positive neointimal cells that transmission electron microscopy (TEM) showed to morphologically differ from medial SMCs. TEM of the neointima further showed presence of elongated deposits of amorphous elastin and presence of nascent, but not mature elastic fibers. These structures appeared to be deficient in at least one microfibrillar component, fibrillin-1, which is critical to mature elastic fiber assembly. The substantial production of elastin and elastic fiber-like structures that we observed in the AAA neointima, which was not observed elsewhere within AAA tissues, provides us a unique opportunity to capitalize on this auto-regenerative phenomenon and direct it from the standpoint of matrix organization towards restoring healthy aortic matrix structure, mechanics, and function. PMID:24799390

  17. Expression of extracellular matrix metalloproteinase inducer (EMMPRIN and its related extracellular matrix degrading enzymes in the endometrium during estrous cycle and early gestation in cattle

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    Hosoe Misa

    2010-06-01

    Full Text Available Abstract Background Extracellular matrix metalloproteinase inducer (EMMPRIN regulates several biological functions involving the modulation of cell behaviors via cell-cell and cell-matrix interactions. According to its diverse functions, we hypothesized that EMMPRIN may play an important role in endometrial remodeling and establishment of pregnancy in cow. Methods In this study, endometrial tissues from the cyclic cows during before ovulation, after ovulation and middle of estrous cycle; and pregnant endometrial tissues from Day 19 to 35 of gestation have been used. Expression of mRNA was analyzed by RT-PCR, qPCR and in situ hybridization whereas protein expression by immunohistochemistry and western blot analysis. Results EMMPRIN mRNA was expressed in both cyclic and pregnant endometrium and significantly higher in the endometrium at Day 35 of gestation than the cyclic endometrium. In Western blot analysis, an approximately 65 kDa band was detected in the endometrium, and approximately 51 kDa in the cultured bovine epithelial cells and BT-1 cells, respectively. Both in situ hybridization and immunohistochemistry data showed that EMMPRIN was primarily expressed in luminal and glandular epithelium with strong staining on Day 19 conceptus. At Day 19 of gestation, expression of EMMPRIN mRNA on luminal epithelium was decreased than that observed at middle of estrous cycle, however, on Day 30 of gestation, slightly increased expression was found at the site of placentation. Expression of matrix metalloproteinase-2 (MMP-2 and MMP-14 mRNA were mainly detected in stroma and their expression also decreased at Day 19 of gestation however it was also expressed at the site of placentation at Day 30 of gestation as observed for EMMPRIN. Expression of MMP-1 or -9 mRNA was very low and was below the detection limit in the cyclic and pregnant endometrium. Conclusion EMMPRIN from the luminal epithelium may regulate the expression of stromal MMP-2 and -14

  18. "Tipping" extracellular matrix remodeling towards regression of liver fibrosis

    DEFF Research Database (Denmark)

    Magdaleno, Fernando; Schierwagen, Robert; Uschner, Frank E

    2018-01-01

    Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established...... fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration...

  19. Matrix metalloproteinases (MMPs) in the endometrium of bitches.

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    Chu Py, Po-yin; Salamonsen, L A; Lee, C S; Wright, P J

    2002-03-01

    The relationships between activities of matrix metalloproteinases (MMPs) in the canine uterus and the occurrence of degeneration of the luminal epithelium, cystic endometrial hyperplasia, pyometra and uterine remodelling post partum were determined. Mature bitches (n = 10) were ovariectomized, treated with hormones (oestradiol benzoate, progestagen) and investigated at stages simulating pro-oestrus (n = 2), oestrus (n = 2), dioestrus (n = 2), and mid- (n = 2) and late (n = 2) anoestrus (3 and 9 weeks, respectively, after cessation of treatment with progestagen). Untreated bitches (n = 1 per group) served as controls (Expt 1). An additional 10 ovariectomized bitches, at the end of treatment-induced simulated dioestrus, were treated each day for a further 3 weeks either with the same dose (standard dose, n = 3), a decreased dose (n = 3) or an increased dose (n = 3) of progestagen, or no treatment (withdrawal dose, n = 1). These bitches were then investigated (Expt 2). A suture was placed in the lumen of one uterine horn of another five bitches at ovariectomy. Three of these bitches were treated to induce simulated dioestrus and two bitches served as untreated controls. In the hormone-treated bitches, the suture resulted in cystic endometrial hyperplasia in one bitch and in cystic endometrial hyperplasia with pyometra in two bitches. The control bitches showed no cystic endometrial hyperplasia or pyometra (Expt 3). Four intact bitches were studied at 2 (n = 1), 3 (n = 2) and 11 (n = 1) weeks post partum. Uterine tissues were also collected from two bitches with naturally occurring cystic endometrial hyperplasia with pyometra (Expt 4). All uteri were examined histologically and the activities of MMP-2, -7 and -9 (latent and active forms) were assessed using zymography of extracts of endometrium. In Expts 1 and 2, marked degeneration of the luminal epithelium in six of 25 bitches (simulated mid-anoestrus, withdrawal dose and decreased dose groups) was not associated

  20. 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.

  1. Aberrant DNA methylation of matrix remodeling and cell adhesion related genes in pterygium.

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    Andri K Riau

    Full Text Available BACKGROUND: Pterygium is a common ocular surface disease characterized by abnormal epithelial and fibrovascular proliferation, invasion, and matrix remodeling. This lesion, which migrates from the periphery to the center of the cornea, impairs vision and causes considerable irritation. The mechanism of pterygium formation remains ambiguous, and current treatment is solely surgical excision, with a significant risk of recurrence after surgery. Here, we investigate the role of methylation in DNA sequences that regulate matrix remodeling and cell adhesion in pterygium formation. METHODOLOGY/PRINCIPAL FINDINGS: Pterygium and uninvolved conjunctiva samples were obtained from the same eye of patients undergoing surgery. The EpiTYPER Sequenom technology, based on differential base cleavage and bisulfite sequencing was used to evaluate the extent of methylation of 29 matrix and adhesion related genes. In pterygium, three CpG sites at -268, -32 and -29 bp upstream of transglutaminase 2 (TGM-2 transcription initiation were significantly hypermethylated (p<0.05, whereas hypomethylation was detected at CpGs +484 and +602 bp downstream of matrix metalloproteinase 2 (MMP-2 transcription start site, and -809, -762, -631 and -629 bp upstream of the CD24 transcription start site. RT-qPCR, western blot and immunofluorescent staining showed that transcript and protein expression were reduced for TGM-2 and increased for MMP-2 and CD24. Inhibition of methylation in cultured conjunctival epithelial cells increased these transcripts. CONCLUSIONS/SIGNIFICANCE: We found regions of aberrant DNA methylation which were consistent with alteration of TGM-2, MMP-2, and CD24 transcript and protein expression, and that inhibition of methylation in cultured cells can increase the expression of these genes. Since these genes were related to cell adhesion and matrix remodeling, dysregulation may lead to fibroblastic and neovascular changes and pterygium formation. These results

  2. Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery

    NARCIS (Netherlands)

    Pasterkamp, G.; Schoneveld, A. H.; Hijnen, D. J.; de Kleijn, D. P.; Teepen, H.; van der Wal, A. C.; Borst, C.

    2000-01-01

    Atherosclerotic luminal narrowing is determined by plaque mass and the mode of geometrical remodeling. Recently, we reported that the type of atherosclerotic remodeling is associated with the presence of histological markers for plaque vulnerability. Inflammation and matrix degrading proteases

  3. 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...

  4. 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.

  5. Matrix Remodeling During Intervertebral Disc Growth and Degeneration Detected by Multichromatic FAST Staining

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    Leung, Victor Y.L.; Chan, Wilson C.W.; Hung, Siu-Chun; Cheung, Kenneth M.C.; Chan, Danny

    2009-01-01

    Various imaging techniques have been used to assess degeneration of the intervertebral disc, including many histological methods, but cartilage-oriented histological stains do not clearly show the comparatively complex structures of the disc. In addition, there is no integrated method to assess efficiently both the compartmental organization and matrix composition in disc samples. In this study, a novel histological method, termed FAST staining, has been developed to investigate disc growth and degeneration by sequential staining with fast green, Alcian blue, Safranin-O, and tartrazine to generate multichromatic histological profiles (FAST profiles). This identifies the major compartments of the vertebra-disc region, including the cartilaginous endplate and multiple zones of the annulus fibrosus, by specific FAST profile patterns. A disc degeneration model in rabbit established using a previously described puncture method showed gradual but profound alteration of the FAST profile during disc degeneration, supporting continual alteration of glycosaminoglycan. Changes of the FAST profile pattern in the nucleus pulposus and annulus fibrosus of the postnatal mouse spine suggested matrix remodeling activity during the growth of intervertebral discs. In summary, we developed an effective staining method capable of defining intervertebral disc compartments in detail and showing matrix remodeling events within the disc. The FAST staining method may be used to develop a histopathological grading system to evaluate disc degeneration or malformation. (J Histochem Cytochem 57:249–256, 2009) PMID:19001641

  6. Quantification of fibronectin as a method to assess ex vivo extracellular matrix remodeling

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    Bager, Cecilie Liv; Gudmann, N.; Willumsen, N.

    2016-01-01

    Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components...... of the ECM is fibronectin. Fibronectin serves as an adhesion molecule anchoring cells to the underlying basement membrane through direct interaction with integrin receptors. Fibronectin hereby modulates the properties of the ECM and affects cellular processes. Quantification of fibronectin remodeling could...... therefore be used to assess the changes in the ECM that occur during progression of fibro-proliferative pathologies. Ex vivo models are becoming state-of-the-art tools to study ECM remodeling as the cellular composition and the organization of the ECM are preserved. Ex vivo models may therefore...

  7. Specific extracellular matrix remodeling signature of colon hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Maguy Del Rio

    Full Text Available To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.

  8. Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice

    DEFF Research Database (Denmark)

    Barascuk, N; Vassiliadis, E; Zheng, Qiuju

    2011-01-01

    Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA...

  9. Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution.

    Directory of Open Access Journals (Sweden)

    Andrea Baiocchini

    Full Text Available Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis. Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

  10. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    International Nuclear Information System (INIS)

    Garcia, Larissa Ferraz; Mataveli, Fábio D’Aguiar; Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell; Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva

    2015-01-01

    Evaluate the effects of VEGF_1_6_5 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF_1_6_5 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF_1_6_5. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF_1_6_5, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF_1_6_5 seems to provide a protective effect in the treatment of acute myocardial infarct

  11. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Larissa Ferraz [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Mataveli, Fábio D’Aguiar [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva [Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2015-07-01

    Evaluate the effects of VEGF{sub 165} gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF{sub 165} treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF{sub 165}. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF{sub 165}, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF{sub 165} seems to provide a protective effect in the treatment of acute myocardial infarct.

  12. The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis

    OpenAIRE

    Yang, Mei; Jiang, Chunfan; Chen, Hua; Nian, Yan; Bai, Zhimiao; Ha, Chunfang

    2015-01-01

    Background Endometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration. Methods We performed primary culture of EECs and investigated the expression o...

  13. Extracellular matrix remodeling and matrix metalloproteinase inhibition in visceral adipose during weight cycling in mice.

    Science.gov (United States)

    Caria, Cíntia Rabelo E Paiva; Gotardo, Érica Martins Ferreira; Santos, Paola Souza; Acedo, Simone Coghetto; de Morais, Thainá Rodrigues; Ribeiro, Marcelo Lima; Gambero, Alessandra

    2017-10-15

    Extracellular matrix (ECM) remodeling is necessary for a health adipose tissue (AT) expansion and also has a role during weight loss. We investigate the ECM alteration during weight cycling (WC) in mice and the role of matrix metalloproteinases (MMPs) was assessed using GM6001, an MMP inhibitor, during weight loss (WL). Obesity was induced in mice by a high-fat diet. Obese mice were subject to caloric restriction for WL followed by reintroduction to high-fat diet for weight regain (WR), resulting in a WC protocol. In addition, mice were treated with GM6001 during WL period and the effects were observed after WR. Activity and expression of MMPs was intense during WL. MMP inhibition during WL results in inflammation and collagen content reduction. MMP inhibition during WL period interferes with the period of subsequent expansion of AT resulting in improvements in local inflammation and systemic metabolic alterations induced by obesity. Our results suggest that MMPs inhibition could be an interesting target to improve adipose tissue inflammation during WL and to support weight cyclers. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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.

  15. Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix

    DEFF Research Database (Denmark)

    Kehlet, Stephanie N.; Willumsen, Nicholas; Armbrecht, Gabriele

    2018-01-01

    The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small...... collagen fragments are released into the circulation, which act as important biomarkers in the study of certain tissue-related remodeling factors in health and disease. The aim of this study was to establish an age-related collagen turnover profile of the main collagens of the interstitial matrix (type I...... an increased turnover. In summary, collagen turnover is affected by age and sex with the interstitial matrix and the basement membrane being differently regulated. The observed changes needs to be accounted for when measuring ECM related biomarkers in clinical studies....

  16. Macrophage-mediated proteolytic remodeling of the extracellular matrix in atherosclerosis results in neoepitopes

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Barascuk, Natasha; Register, Thomas

    2010-01-01

    in almost all stages of atherosclerosis, by both initiating atherosclerotic plaques and degrading them through the secretion of proteolytic enzymes leading to rupture. This review summarizes the literature on the role of macrophages and their proteolytic activity on proteins in the extracellular matrix (ECM......) of the atherosclerotic plaque with a view to suggest a novel approach for identification of vulnerable plaques and turnover by the use of a new type of biomarker. The PubMed database was searched using the terms macrophages, foam cells, atherosclerosis, CVD, ECM remodeling, biomarker, neoepitope, matrix...... of the constituents of the ECM of the atherosclerotic plaque. At present it is not clear which proteases play pivotal roles at distinct stages of pathogenesis, rather that the combined proteolytic potential with some proteases at early stages and other at later stages may result in plaque rupture. This macrophage...

  17. The planar cell polarity protein VANGL2 coordinates remodeling of the extracellular matrix.

    Science.gov (United States)

    Williams, B Blairanne; Mundell, Nathan; Dunlap, Julie; Jessen, Jason

    2012-07-01

    Understanding how planar cell polarity (PCP) is established, maintained, and coordinated in migrating cell populations is an important area of research with implications for both embryonic morphogenesis and tumor cell invasion. We recently reported that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell surface level of membrane type-1 matrix metalloproteinase (MMP14 or MT1-MMP). Here, we further discuss these findings in terms of extracellular matrix (ECM) remodeling, cell migration, and zebrafish gastrulation. We also demonstrate that VANGL2 function impacts the focal degradation of ECM by human cancer cells including the formation or stability of invadopodia. Together, our findings implicate MMP14 as a downstream effector of VANGL2 signaling and suggest a model whereby the regulation of pericellular proteolysis is a fundamental aspect of PCP in migrating cells.

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

    Science.gov (United States)

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

    2017-01-01

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

  19. Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on MMP expression and extracellular matrix remodeling by fibroblasts

    NARCIS (Netherlands)

    Zhang, Y.; Lin, Z.; Foolen, J.; Schoen, I.; Santoro, A.; Zenobi-Wong, M.; Vogel, Viola

    2014-01-01

    Early wound healing is associated with fibroblasts assembling a provisional fibronectin-rich extracellular matrix (ECM), which is subsequently remodeled and interlaced by type I collagen. This exposes fibroblasts to time-variant sets of matrices during different stages of wound healing. Our goal was

  20. Granulocytes and vascularization regulate uterine bleeding and tissue remodeling in a mouse menstruation model.

    Directory of Open Access Journals (Sweden)

    Astrid Menning

    Full Text Available Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery.

  1. Cytoskeletal remodeling of connective tissue fibroblasts in response to static stretch is dependent on matrix material properties

    Science.gov (United States)

    Abbott, Rosalyn D; Koptiuch, Cathryn; Iatridis, James C; Howe, Alan K; Badger, Gary J; Langevin, Helene M

    2012-01-01

    In areolar “loose” connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in and dissociated from areolar and dense connective tissue in response to 2 hours of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large “sheet-like” morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells’ tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues. PMID:22552950

  2. ECM remodeling and its plasticity

    Science.gov (United States)

    Feng, Jingchen; Jones, Christopher A. R.; Cibula, Matthew; Mao, Xiaoming; Sander, Leonard M.; Levine, Herbert; Sun, Bo

    The mechanical interactions between cells and Extracellular Matrix (ECM) are of great importance in many cellular processes. These interactions are reciprocal, i.e. contracting cells pull and reorganize the surrounding matrix, while the remodeled matrix feeds back to regulate cell activities. Recent experiments show in collagen gels with densely distributed cells, aligned fiber bundles are formed in the direction between neighboring cells. Fibers flow into the center region between contracting cell pairs in this process, which causes the concentration of fibers in the fiber bundles to become significantly enhanced. Using an extended lattice-based model, we show that viscoelasticity plays an essential role in ECM remodeling and contributes to the enhanced concentration in fiber bundles. We further characterize ECM plasticity within our model and verify our results with rheometer experiments.

  3. THE ROLE OF MATRIX METALLOPROTEINASES IN PROCESSES OF HEART RE-MODELING IN CHILDREN WITH RESTRICTIVE CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    T.V. Bershova

    2009-01-01

    Full Text Available Restrictive cardiomyopathy (RCMP is heart disorder with unclear etiology; it can be characterized as disease with disorder of diastolic myocardium function of left ventricle, conditioned by restriction. The chronic heart failure as a syndrome of RCMP can develop as a result of disbalance in system of complex biochemical, structural, and geometrical mechanisms of myocardium re-modeling. Extra cellular matrix play significant role in heart structure and geometry breaking. The destruction of heart is realized by matrix metalloproteinases (MMP. The activity of MMP, in its turn, is controlled by its tissue inhibitors. The present study analyzed the role of MMP in process of collagen’s synthesis and catabolism deregulation, myocardium fibrosis, change of heart chambers, and development of diastolic dysfunction in children with RCMP.Key words: children, chronic heart failure, restrictive cardiomyopathy, matrix metalloproteinases.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:36-39

  4. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

    Directory of Open Access Journals (Sweden)

    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.

  5. YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration

    DEFF Research Database (Denmark)

    Yui, Shiro; Azzolin, Luca; Maimets, Martti

    2018-01-01

    by remodeling the extracellular matrix (ECM), increased FAK/Src signaling, and ultimately YAP/TAZ activation. In a defined cell culture system recapitulating the extracellular matrix remodeling observed in vivo, we show that a collagen 3D matrix supplemented with Wnt ligands is sufficient to sustain endogenous...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Platelet-rich plasma and chronic wounds: remaining fibronectin may influence matrix remodeling and regeneration success.

    Science.gov (United States)

    Moroz, Andrei; Deffune, Elenice

    2013-11-01

    Platelet-rich plasma has been largely used as a therapeutic option for the treatment of chronic wounds of different etiologies. The enhanced regeneration observed after the use of platelet-rich plasma has been systematically attributed to the growth factors that are present inside platelets' granules. We hypothesize that the remaining plasma and platelet-bound fibronectin may act as a further bioactive protein in platelet-rich plasma preparations. Recent reports were analyzed and presented as direct evidences of this hypotheses. Fibronectin may directly influence the extracellular matrix remodeling during wound repair. This effect is probably through matrix metalloproteinase expression, thus exerting an extra effect on chronic wound regeneration. Physicians should be well aware of the possible fibronectin-induced effects in their future endeavors with PRP in chronic wound treatment. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-05-15

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

  10. Public data mining plus domestic experimental study defined involvement of the old-yet-uncharacterized gene matrix-remodeling associated 7 (MXRA7) in physiopathology of the eye.

    Science.gov (United States)

    Jia, Changkai; Zhang, Feng; Zhu, Ying; Qi, Xia; Wang, Yiqiang

    2017-10-20

    Matrix-remodeling associated 7 (MXRA7) gene was first reported in 2002 and named so for its co-expression with several genes known to relate with matrix-remodeling. However, not any studies had been intentionally performed to characterize this gene. We started defining the functions of MXRA7 by integrating bioinformatics analysis and experimental study. Data mining of MXRA7 expression in BioGPS, Gene Expression Omnibus and EurExpress platforms highlighted high level expression of Mxra7 in murine ocular tissues. Real-time PCR was employed to measure Mxra7 mRNA in tissues of adult C57BL/6 mice and demonstrated that Mxra7 was preferentially expressed at higher level in retina, corneas and lens than in other tissues. Then the inflammatory corneal neovascularization (CorNV) model and fungal corneal infections were induced in Balb/c mice, and mRNA levels of Mxra7 as well as several matrix-remodeling related genes (Mmp3, Mmp13, Ecm1, Timp1) were monitored with RT-PCR. The results demonstrated a time-dependent Mxra7 under-expression pattern (U-shape curve along timeline), while all other matrix-remodeling related genes manifested an opposite changes pattern (dome-shape curve). When limited data from BioGPS concerning human MXRA7 gene expression in human tissues were looked at, it was found that ocular tissue was also the one expressing highest level of MXRA7. To conclude, integrative assay of MXRA7 gene expression in public databank as well as domestic animal models revealed a selective high expression MXRA7 in murine and human ocular tissues, and its change patterns in two corneal disease models implied that MXRA7 might play a role in pathological processes or diseases involving injury, neovascularization and would healing. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Magnitude and duration of stretch modulate fibroblast remodeling.

    Science.gov (United States)

    Balestrini, Jenna L; Billiar, Kristen L

    2009-05-01

    Mechanical cues modulate fibroblast tractional forces and remodeling of extracellular matrix in healthy tissue, healing wounds, and engineered matrices. The goal of the present study is to establish dose-response relationships between stretch parameters (magnitude and duration per day) and matrix remodeling metrics (compaction, strength, extensibility, collagen content, contraction, and cellularity). Cyclic equibiaxial stretch of 2-16% was applied to fibroblast-populated fibrin gels for either 6 h or 24 h/day for 8 days. Trends in matrix remodeling metrics as a function of stretch magnitude and duration were analyzed using regression analysis. The compaction and ultimate tensile strength of the tissues increased in a dose-dependent manner with increasing stretch magnitude, yet remained unaffected by the duration in which they were cycled (6 h/day versus 24 h/day). Collagen density increased exponentially as a function of both the magnitude and duration of stretch, with samples stretched for the reduced duration per day having the highest levels of collagen accumulation. Cell number and failure tension were also dependent on both the magnitude and duration of stretch, although stretch-induced increases in these metrics were only present in the samples loaded for 6 h/day. Our results indicate that both the magnitude and the duration per day of stretch are critical parameters in modulating fibroblast remodeling of the extracellular matrix, and that these two factors regulate different aspects of this remodeling. These findings move us one step closer to fully characterizing culture conditions for tissue equivalents, developing improved wound healing treatments and understanding tissue responses to changes in mechanical environments during growth, repair, and disease states.

  12. Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2017-01-01

    Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

  13. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de

    2003-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  14. Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on MMP expression and extracellular matrix remodeling by fibroblasts.

    Science.gov (United States)

    Zhang, Yang; Lin, Zhe; Foolen, Jasper; Schoen, Ingmar; Santoro, Alberto; Zenobi-Wong, Marcy; Vogel, Viola

    2014-11-01

    Early wound healing is associated with fibroblasts assembling a provisional fibronectin-rich extracellular matrix (ECM), which is subsequently remodeled and interlaced by type I collagen. This exposes fibroblasts to time-variant sets of matrices during different stages of wound healing. Our goal was thus to gain insight into the ECM-driven functional regulation of human foreskin fibroblasts (HFFs) being either anchored to a fibronectin (Fn) or to a collagen-decorated matrix, in the absence or presence of cyclic mechanical strain. While the cells reoriented in response to the onset of uniaxial cyclic strain, cells assembled exogenously added Fn with a preferential Fn-fiber alignment along their new orientation. Exposure of HFFs to exogenous Fn resulted in an increase in matrix metalloproteinase (MMP) expression levels, i.e. MMP-15 (RT-qPCR), and MMP-9 activity (zymography), while subsequent exposure to collagen slightly reduced MMP-15 expression and MMP-9 activity compared to Fn-exposure alone. Cyclic strain upregulated Fn fibrillogenesis and actin stress fiber formation, but had comparatively little effect on MMP activity. We thus propose that the appearance of collagen might start to steer HFFs towards homeostasis, as it decreased both MMP secretion and the tension of Fn matrix fibrils as assessed by Fluorescence Resonance Energy Transfer. These results suggest that HFFs might have a high ECM remodeling or repair capacity in contact with Fn alone (early event), which is reduced in the presence of Col1 (later event), thereby down-tuning HFF activity, a processes which would be required in a tissue repair process to finally reach tissue homeostasis. Copyright © 2014. Published by Elsevier B.V.

  15. Endometrial cancer.

    Science.gov (United States)

    Porter, Stephanie

    2002-08-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  17. Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice.

    Science.gov (United States)

    Kyriakides, T R; Zhu, Y H; Yang, Z; Huynh, G; Bornstein, P

    2001-10-01

    The matricellular angiogenesis inhibitor, thrombospondin (TSP) 2, has been shown to be an important modulator of wound healing and the foreign body response. Specifically, TSP2-null mice display improved healing with minimal scarring and form well-vascularized foreign body capsules. In this study we performed subcutaneous implantation of sponges and investigated the resulting angiogenic and fibrogenic responses. Histological and immunohistochemical analysis of sponges, excised at 7, 14, and 21 days after implantation, revealed significant differences between TSP2-null and wild-type mice. Most notably, TSP2-null mice exhibited increased angiogenesis and fibrotic encapsulation of the sponge. However, invasion of dense tissue was compromised, even though its overall density was increased. Furthermore, histomorphometry and biochemical assays demonstrated a significant increase in the extracellular distribution of matrix metalloproteinase (MMP) 2, but no change in the levels of active transforming growth factor-beta(1). The alterations in neovascularization, dense tissue invasion, and MMP2 in TSP2-null mice coincided with the deposition of TSP2 in the extracellular matrix of wild-type animals. These observations support the proposed role of TSP2 as a modulator of angiogenesis and matrix remodeling during tissue repair. In addition, they provide in vivo evidence for a newly proposed function of TSP2 as a modulator of extracellular MMP2 levels.

  18. The role of adhesive molecules in endometrial cancer: part II

    Directory of Open Access Journals (Sweden)

    Andrzej Malinowski

    2010-12-01

    Full Text Available The carcinogenesis is a result of both functional and structural disorders in the tissue. It initiates as a mutationin a gene encoding protein that is essential for cellular function. The subsequent cascade of eventsleads to accumulation of mutations and loss of cellular function. The cell loses its tissue-specific morphology,disconnects from other cells and extracellular matrix and migrates – the invasion begins. It is now clear thatadhesive molecules are a key player in this cascade. These proteins of the cell membrane surface are responsiblefor attachment of the cells to each other and to the extracellular matrix. These interactions are crucial forboth structural and functional tissue organization. Lack of this homeostasis destroys the tissue architectureand impairs its function and results in invasion. Abnormal expression of adhesive molecules was reported in allexamined cancers, including endometrial cancer.Endometrial cancer is the most common gynaecological cancer in developed countries. Although in many casesdiagnosed and treated in early stages, and thus with good results, some patients cannot be cured. Completeknowledge of the pathogenesis of the disease will be helpful in identifying the patients with negative prognosticfactors, increased risk of recurrence and, perhaps, to find other therapeutic options. In the paper we are trying tosum up the up-to-date knowledge of the role of adhesive molecules in pathogenesis of endometrial cancer.

  19. Correlation between genetic polymorphism of matrix metalloproteinase-9 in patients with coronary artery disease and cardiac remodeling.

    Science.gov (United States)

    Yu, Qibin; Li, Hanmei; Li, Linlin; Wang, Shaoye; Wu, Yongbo

    2015-01-01

    To explore the correlation between genetic polymorphism of matrix metalloproteinase-9 (MMP-9) in patients with coronary artery disease (CAD) and cardiac remodeling. A total of 272 subjects who received coronary angiography in our hospital from July 2008 to September 2013 were selected, including 172 CAD patients (CAD group) and another 100 ones (control group). Both groups were subjected to MMP-9 and ultrasonic detections to determine vascular remodeling and atherosclerotic plaques. C1562G polymorphism of MMP-9 gene was detected, and correlation with vascular remodeling and atherosclerotic plaque was analyzed. Serum MMP-9 level of CAD group (330.87±50.39 ng/ml) was significantly higher than that of control group (134.87±34.02 ng/ml) (P<0.05). Compared with control group, CAD group had significantly higher intima-media thickness, and significantly lower systolic peak velocity, mean systolic velocity and end-diastolic velocity (P<0.05). Total area of stenotic blood vessels was 67.34±22.98 mm(2), while that of control blood vessels was 64.00±20.83 mm(2). G/G, G/C and C/C genotype frequencies of MMP-9 differed significantly in the two groups (P<0.05). G and C allele frequencies of CAD group (70.9% and 29.1%) were significantly different from those of control group (50.0% and 50.0%) (P<0.05). G/G, G/C and C/C genotypes were manifested as lipid-rich, fibrous and calcified or ulcerated plaques respectively. Total area of stenotic blood vessels of G/G genotype significantly exceeded those of G/C and C/C genotypes (P<0.05), whereas the latter two had no significant differences. CAD promoted 1562C-G transformation of MMP-9 gene into genetic polymorphism, thus facilitating arterial remodeling and increasing unstable atherosclerotic plaques.

  20. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    Science.gov (United States)

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  1. Premature loss of bone remodeling compartment canopies is associated with deficient bone formation

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent

    2011-01-01

    A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling, were proposed to be critical players in this mechanism. Here, we provide...

  2. Left ventricular remodeling in preclinical experimental mitral regurgitation of dogs.

    Science.gov (United States)

    Dillon, A Ray; Dell'Italia, Louis J; Tillson, Michael; Killingsworth, Cheryl; Denney, Thomas; Hathcock, John; Botzman, Logan

    2012-03-01

    Dogs with experimental mitral regurgitation (MR) provide insights into the left ventricular remodeling in preclinical MR. The early preclinical left ventricular (LV) changes after mitral regurgitation represent progressive dysfunctional remodeling, in that no compensatory response returns the functional stroke volume (SV) to normal even as total SV increases. The gradual disease progression leads to mitral annulus stretch and enlargement of the regurgitant orifice, further increasing the regurgitant volume. Remodeling with loss of collagen weave and extracellular matrix (ECM) is accompanied by stretching and hypertrophy of the cross-sectional area and length of the cardiomyocyte. Isolated ventricular cardiomyocytes demonstrate dysfunction based on decreased cell shortening and reduced intracellular calcium transients before chamber enlargement or decreases in contractility in the whole heart can be clinically appreciated. The genetic response to increased end-diastolic pressure is down-regulation of genes associated with support of the collagen and ECM and up-regulation of genes associated with matrix remodeling. Experiments have not demonstrated any beneficial effects on remodeling from treatments that decrease afterload via blocking the renin-angiotensin system (RAS). Beta-1 receptor blockade and chymase inhibition have altered the progression of the LV remodeling and have supported cardiomyocyte function. The geometry of the LV during the remodeling provides insight into the importance of regional differences in responses to wall stress. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen.

    Science.gov (United States)

    Thievessen, Ingo; Fakhri, Nikta; Steinwachs, Julian; Kraus, Viola; McIsaac, R Scott; Gao, Liang; Chen, Bi-Chang; Baird, Michelle A; Davidson, Michael W; Betzig, Eric; Oldenbourg, Rudolf; Waterman, Clare M; Fabry, Ben

    2015-11-01

    Vinculin is filamentous (F)-actin-binding protein enriched in integrin-based adhesions to the extracellular matrix (ECM). Whereas studies in 2-dimensional (2D) tissue culture models have suggested that vinculin negatively regulates cell migration by promoting cytoskeleton-ECM coupling to strengthen and stabilize adhesions, its role in regulating cell migration in more physiologic, 3-dimensional (3D) environments is unclear. To address the role of vinculin in 3D cell migration, we analyzed the morphodynamics, migration, and ECM remodeling of primary murine embryonic fibroblasts (MEFs) with cre/loxP-mediated vinculin gene disruption in 3D collagen I cultures. We found that vinculin promoted 3D cell migration by increasing directional persistence. Vinculin was necessary for persistent cell protrusion, cell elongation, and stable cell orientation in 3D collagen, but was dispensable for lamellipodia formation, suggesting that vinculin-mediated cell adhesion to the ECM is needed to convert actin-based cell protrusion into persistent cell shape change and migration. Consistent with this finding, vinculin was necessary for efficient traction force generation in 3D collagen without affecting myosin II activity and promoted 3D collagen fiber alignment and macroscopical gel contraction. Our results suggest that vinculin promotes directionally persistent cell migration and tension-dependent ECM remodeling in complex 3D environments by increasing cell-ECM adhesion and traction force generation. © FASEB.

  4. The differences in RCAS1 and DFF45 endometrial expression between late proliferative, early secretory, and mid-secretory cycle phases.

    Directory of Open Access Journals (Sweden)

    Jerzy Sikora

    2008-04-01

    Full Text Available RCAS1 expression is related to the regulation of activated immune cells and to connective tissue remodeling within the endometrium. DFF45 seems to play an important role in the apoptotic process, most likely by acting through the regulation of DNA fragmentation. Its expression changes within the endometrium seem to be related to the resistance of endometrial cells to apoptosis. The aim of the present study was to evaluate RCAS1 and DFF45 endometrial expressions during ovulation and the implantation period. RCAS1 and DFF45 expression was assessed by the Western-blot method in endometrial tissue samples obtained from 20 patients. The tissue samples were classified according to the menstrual cycle phases in which they were collected, with a division into three phases: late proliferative, early secretory, and mid-secretory. The lowest level of RCAS1 and the highest level of DFF45 endometrial expression was found during the early secretory cycle phase. Statistically significantly higher RCAS1 and statistically significantly lower DFF45 endometrial expression was identified in the endometrium during the late proliferative as compared to the early secretory cycle phase. Moreover, statistically significantly higher RCAS1 and statistically significantly lower DFF45 expression was found in the endometrium during the mid-secretory as compared to the early secretory cycle phase. The preparation for implantation process in the endometrium is preceded by dynamic changes in endometrial ECM and results from the proper interaction between endometrial and immune cells. The course of this process is conditioned by the immunomodulating activity of endometrial cells and their resistance to immune-mediated apoptosis. These dynamic changes are closely related to RCAS1 and DFF45 expression alterations.

  5. Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Keith Dadson

    Full Text Available Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM remodeling in response to pressure overload (PO. Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO and wild-type (WT mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson's trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects.

  6. Markers of Airway Remodeling in Bronchopulmonary Diseases

    Directory of Open Access Journals (Sweden)

    O.Ye. Chernyshova

    2014-10-01

    Full Text Available The article presents information about markers of airway remodeling in bronchopulmonary diseases. There is described the influence of matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase, transforming growth factor, collagen autoantibodies III type, endothelin-1 on the processes of morphological airway reconstruction as smooth muscle hypertrophy, enhanced neovascularization, epithelial cell hyperplasia, collagen deposition, compaction of the basal membrane, observed in bronchial asthma.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Renuka Devi Balakrishnan

    2016-11-01

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

  9. Expression of Genes Involved in Cellular Adhesion and Extracellular Matrix Remodeling Correlates with Poor Survival of Patients with Renal Cancer.

    Science.gov (United States)

    Boguslawska, Joanna; Kedzierska, Hanna; Poplawski, Piotr; Rybicka, Beata; Tanski, Zbigniew; Piekielko-Witkowska, Agnieszka

    2016-06-01

    Renal cell carcinoma is the most common highly metastatic kidney malignancy. Adhesion has a crucial role in the metastatic process. TGF (transforming growth factor)-β1 is a pleiotropic cytokine that influences cancerous transformation. We hypothesized that 1) changes in the expression of adhesion related genes may influence survival rate of patients with renal cell carcinoma and 2) TGF-β1 may contribute to changed expression of adhesion related genes. Two-step quantitative real-time polymerase chain reaction arrays were used to analyze the expression of adhesion related genes in 77 tumors and matched pair controls. The prognostic significance of genes was evaluated in TCGA (The Cancer Genome Atlas) data on 468 patients with renal cell carcinoma. Quantitative real-time polymerase chain reaction and Western blot were applied for TGF-β1 analysis. TGF-β1 mediated regulation of gene expression was analyzed by TGF-β1 supplementation of Caki-2 cells and quantitative real-time polymerase chain reaction. The expression of 19 genes related to adhesion and extracellular matrix remodeling was statistically significantly disturbed in renal cell carcinoma compared with controls. The 10-gene expression signature (COL1A1, COL5A1, COL11A1, FN1, ICAM1, ITGAL, ITGAM, ITGB2, THBS2 and TIMP1) correlated with poor survival (HR 2.85, p = 5.7e-10). TGF-β1 expression was 22 times higher in renal cell carcinoma than in controls (p adhesion and extracellular matrix remodeling develops early during renal cell carcinoma carcinogenesis and correlates with poor survival. TGF-β1 contributes to changed expression of extracellular matrix and adhesion related genes. Bioinformatic analysis performed on a broad panel of cancers of nonkidney origin suggests that disturbed expression of genes related to extracellular matrix and adhesion may be a universal feature of cancerous progression. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All

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

    Directory of Open Access Journals (Sweden)

    Yu-Li Chen

    2009-06-01

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

  11. 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)

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

    Directory of Open Access Journals (Sweden)

    Gang Feng

    2014-01-01

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

  13. Interleukin-1β regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    International Nuclear Information System (INIS)

    Zitta, Karina; Brandt, Berenice; Wuensch, Annegret; Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

    2010-01-01

    Research highlights: → Levels of IL-1β are increased in the pig myocardium after infarction. → Cultured pig heart cells possess IL-1 receptors. → IL-1β increases cell proliferation of pig heart cells in-vitro. → IL-1β increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. → IL-1β may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1β is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1β on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1β. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1β resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1β plays a major role in the events of tissue remodelling in the heart. Combined with our recently published in vivo data (Meybohm et al., PLoS One

  14. Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    Energy Technology Data Exchange (ETDEWEB)

    Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

    2010-09-03

    Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

  15. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-06-01

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

  17. Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis.

    Science.gov (United States)

    Zhang, Ling; Xiong, Wenqian; Xiong, Yao; Liu, Hengwei; Li, Na; Du, Yu; Liu, Yi

    2016-03-01

    Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease. © 2016 by the Society for the Study of Reproduction, Inc.

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

    Directory of Open Access Journals (Sweden)

    H. Gbelcová

    2015-01-01

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

  19. Genetics of Endometrial Cancers

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Okuda

    2010-01-01

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

  20. MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis

    Directory of Open Access Journals (Sweden)

    Yingmei Wang

    2016-10-01

    Full Text Available Abstract Background Endometrial carcinoma (EC is one of the most common malignancies of the female reproductive system. Migration and invasion inhibitory protein (MIIP gene was recently discovered candidate tumor suppress gene which located at chromosome 1p36.22. 1p36 deletion was found in many types of tumor including EC. In the present study, we will determine the role and mechanism of MIIP in EC metastasis. Methods Immunohistochemistry was used to measure MIIP expression in normal and EC tissue. Both gain-of-function (infection and loss-of-function (siRNA assays were used to alter MIIP expression levels. The effect of MIIP on cell migration and invasion was measured by transwell assay. F-actin immunofluorescence staining was used to observe the cell morphology. The activation of GTP-loaded Rac1 was evaluated by Rac activity assay kit. Immunoprecipitation/WB was used to measure the interaction between MIIP and PAK1. Results We demonstrate that MIIP expression was significantly decreased in EC patients comparing to the normal ones, and decreased MIIP expression in EC tissues is associated with deep myometrial invasion, advanced stage, and the presence of lymph node metastasis. Using both gain-of-function (infection and loss-of-function (siRNA assays, we show that MIIP markedly blocked EC cell migration, whereas loss of MIIP led to increase in EC cell migration. We demonstrate that elevated expression of MIIP resulted in cytoskeleton reorganization with decreased formation of lamellipodia. We also provide evidence that MIIP is a key molecule in directing Rac1 signaling cascades in EC. Ectopically expressed MIIP consistently competed with Rac1-GTP for binding with the PAK1 p21-binding domain. Our data show that MIIP and PAK1 bind each other and that a C-terminal polyproline domain of MIIP is required for PAK1 binding. Deletion of the PAK1-binding domain of MIIP reduced cell migration-inhibiting activity. Conclusions MIIP may function as a tumor

  1. MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis.

    Science.gov (United States)

    Wang, Yingmei; Hu, Limei; Ji, Ping; Teng, Fei; Tian, Wenyan; Liu, Yuexin; Cogdell, David; Liu, Jinsong; Sood, Anil K; Broaddus, Russell; Xue, Fengxia; Zhang, Wei

    2016-10-19

    Endometrial carcinoma (EC) is one of the most common malignancies of the female reproductive system. Migration and invasion inhibitory protein (MIIP) gene was recently discovered candidate tumor suppress gene which located at chromosome 1p36.22. 1p36 deletion was found in many types of tumor including EC. In the present study, we will determine the role and mechanism of MIIP in EC metastasis. Immunohistochemistry was used to measure MIIP expression in normal and EC tissue. Both gain-of-function (infection) and loss-of-function (siRNA) assays were used to alter MIIP expression levels. The effect of MIIP on cell migration and invasion was measured by transwell assay. F-actin immunofluorescence staining was used to observe the cell morphology. The activation of GTP-loaded Rac1 was evaluated by Rac activity assay kit. Immunoprecipitation/WB was used to measure the interaction between MIIP and PAK1. We demonstrate that MIIP expression was significantly decreased in EC patients comparing to the normal ones, and decreased MIIP expression in EC tissues is associated with deep myometrial invasion, advanced stage, and the presence of lymph node metastasis. Using both gain-of-function (infection) and loss-of-function (siRNA) assays, we show that MIIP markedly blocked EC cell migration, whereas loss of MIIP led to increase in EC cell migration. We demonstrate that elevated expression of MIIP resulted in cytoskeleton reorganization with decreased formation of lamellipodia. We also provide evidence that MIIP is a key molecule in directing Rac1 signaling cascades in EC. Ectopically expressed MIIP consistently competed with Rac1-GTP for binding with the PAK1 p21-binding domain. Our data show that MIIP and PAK1 bind each other and that a C-terminal polyproline domain of MIIP is required for PAK1 binding. Deletion of the PAK1-binding domain of MIIP reduced cell migration-inhibiting activity. MIIP may function as a tumor suppressor gene for endometrial carcinoma. MIIP attenuates Rac1

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

    Science.gov (United States)

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

    2017-10-01

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

  3. Matrix Metalloproteinase-2 Activity is Associated with Divergent Regulation of Calponin-1 in Conductance and Resistance Arteries in Hypertension-induced Early Vascular Dysfunction and Remodelling.

    Science.gov (United States)

    Parente, Juliana M; Pereira, Camila A; Oliveira-Paula, Gustavo H; Tanus-Santos, José E; Tostes, Rita C; Castro, Michele M

    2017-10-01

    Matrix metalloproteinase (MMP)-2 participates in hypertension-induced maladaptive vascular remodelling by degrading extra- and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMCs) lead to increased cellular migration and proliferation. As calponin-1 degradation by MMP-2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP-2 activity contributes to early hypertension-induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin-1. The main objective was to analyse whether MMP-2 exerts similar effects on the structure and function of the resistance and conductance arteries during early hypertension. Two-kidney, one-clip (2K-1C) hypertensive male rats and corresponding controls were treated with doxycycline (30 mg/kg/day) or water until reaching one week of hypertension. Systolic blood pressure was increased in 2K-1C rats, and doxycycline did not reduce it. Aortas and mesenteric arteries were analysed. MMP-2 activity and expression were increased in both arteries, and doxycycline reduced it. Significant hypertrophic remodelling and VSMC proliferation were observed in aortas but not in mesenteric arteries of 2K-1C rats. The contractility of mesenteric arteries to phenylephrine was increased in 2K-1C rats, and doxycycline prevented this alteration. The potency of phenylephrine to contract aortas of 2K-1C rats was increased, and doxycycline decreased it. Whereas calponin-1 expression was increased in 2K-1C mesenteric arteries, calponin-1 was reduced in aortas. Doxycycline treatment reverted changes in calponin-1 expression. MMP-2 contributes to hypertrophic remodelling in aortas by decreasing calponin-1 levels, which may result in VSMC proliferation. On the other hand, MMP-2-dependent increased calponin-1 in mesenteric arteries may contribute to vascular hypercontractility in 2K-1C rats. Divergent

  4. 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

  5. Extracellular matrix remodeling and matrix metalloproteinases (ajMMP-2 like and ajMMP-16 like) characterization during intestine regeneration of sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Miao, Ting; Wan, Zixuan; Sun, Lina; Li, Xiaoni; Xing, Lili; Bai, Yucen; Wang, Fang; Yang, Hongsheng

    2017-10-01

    Remodeling of extracellular matrix (ECM) regulated by matrix metalloproteinases (MMPs) is essential for tissue regeneration. In the present study, we used immunohistochemistry (IHC) techniques against ECM components to reveal changes of ECM during intestine regeneration of Apostichopus japonicus. The expression of collagen I and laminin reduced apparently from the eviscerated intestine, while fibronectin exhibited continuous expression in all regeneration stages observed. Meanwhile, we cloned two MMP genes from A. japonicus by RACE PCR. The full-length cDNA of ajMMP-2 like is 2733bp and contains a predicted open reading frame (ORF) of 1716bp encoding 572 amino acids. The full-length cDNA of ajMMP-16 like is 2705bp and contains an ORF of 1452bp encoding 484 amino acids. The predicted protein sequences of each MMP contain two conserved domains, ZnMc_MMP and HX. Homology and phylogenetic analysis revealed that ajMMP-2 like and ajMMP-16 like share high sequence similarity with MMP-2 and MMP-16 from Strongylocentrotus purpuratus, respectively. Then we investigated spatio-temporal expression of ajMMP-2 like and ajMMP-16 like during different regeneration stages by qRT-PCR and IHC. The expression pattern of them showed a roughly opposite trend from that of ECM components. According to our results, a fibronectin-dominate temporary matrix is created in intestine regeneration, and it might provide structural integrity for matrix and promote cell movement. We also hypothesize that ajMMP-2 like and ajMMP-16 like could accelerate cell migration and regulate interaction between ECM components and growth factors. This work provides new evidence of ECM and MMPs involvement in sea cucumber regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 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...

  7. 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.

  8. Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix.

    Science.gov (United States)

    Kehlet, Stephanie N; Willumsen, Nicholas; Armbrecht, Gabriele; Dietzel, Roswitha; Brix, Susanne; Henriksen, Kim; Karsdal, Morten A

    2018-01-01

    The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small collagen fragments are released into the circulation, which act as important biomarkers in the study of certain tissue-related remodeling factors in health and disease. The aim of this study was to establish an age-related collagen turnover profile of the main collagens of the interstitial matrix (type I and III collagen) and basement membrane (type IV collagen) in healthy men and women. By using well-characterized competitive ELISA-assays, we assessed specific fragments of degraded (C1M, C3M, C4M) and formed (PINP, Pro-C3, P4NP7S) type I, III and IV collagen in serum from 617 healthy men and women ranging in ages from 22 to 86. Subjects were divided into 5-year age groups according to their sex and age. Groups were compared using Kruskal-Wallis adjusted for Dunn's multiple comparisons test and Mann-Whitney t-test. Age-specific changes in collagen turnover was most profound for type I collagen. PINP levels decreased in men with advancing age, whereas in women, the level decreased in early adulthood followed by an increase around the age of menopause (age 40-60). Sex-specific changes in type I, III and IV collagen turnover was present at the age around menopause (age 40-60) with women having an increased turnover. In summary, collagen turnover is affected by age and sex with the interstitial matrix and the basement membrane being differently regulated. The observed changes needs to be accounted for when measuring ECM related biomarkers in clinical studies.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yinghua Li

    2015-10-01

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

  11. Lipocalins Are Required for Apical Extracellular Matrix Organization and Remodeling in Caenorhabditis elegans.

    Science.gov (United States)

    Forman-Rubinsky, Rachel; Cohen, Jennifer D; Sundaram, Meera V

    2017-10-01

    A lipid and glycoprotein-rich apical extracellular matrix (aECM) or glycocalyx lines exposed membranes in the body, and is particularly important to protect narrow tube integrity. Lipocalins ("fat cups") are small, secreted, cup-shaped proteins that bind and transport lipophilic cargo and are often found in luminal or aECM compartments such as mammalian plasma, urine, or tear film. Although some lipocalins can bind known aECM lipids and/or matrix metalloproteinases, it is not known if and how lipocalins affect aECM structure due to challenges in visualizing the aECM in most systems. Here we show that two Caenorhabditis elegans lipocalins, LPR-1 and LPR-3, have distinct functions in the precuticular glycocalyx of developing external epithelia. LPR-1 moves freely through luminal compartments, while LPR-3 stably localizes to a central layer of the membrane-anchored glycocalyx, adjacent to the transient zona pellucida domain protein LET-653 Like LET-653 and other C. elegans glycocalyx components, these lipocalins are required to maintain the patency of the narrow excretory duct tube, and also affect multiple aspects of later cuticle organization. lpr-1 mutants cannot maintain a continuous excretory duct apical domain and have misshapen cuticle ridges (alae) and abnormal patterns of cuticular surface lipid staining. lpr-3 mutants cannot maintain a passable excretory duct lumen, properly degrade the eggshell, or shed old cuticle during molting, and they lack cuticle barrier function. Based on these phenotypes, we infer that both LPR-1 and LPR-3 are required to build a properly organized aECM, while LPR-3 additionally is needed for aECM clearance and remodeling. The C. elegans glycocalyx provides a powerful system, amenable to both genetic analysis and live imaging, for investigating how lipocalins and lipids affect aECM structure. Copyright © 2017 by the Genetics Society of America.

  12. 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 ...

  13. A study of extracellular matrix remodeling in aortic heart valves using a novel biaxial stretch bioreactor.

    Science.gov (United States)

    Lei, Ying; Masjedi, Shirin; Ferdous, Zannatul

    2017-11-01

    In aortic valves, biaxial cyclic stretch is known to modulate cell differentiation, extracellular matrix (ECM) synthesis and organization. We designed a novel bioreactor that can apply independent and precise stretch along radial and circumferential directions in a tissue culture environment. While this bioreactor can be used for either native or engineered tissues, this study determined matrix remodeling and strain distribution of aortic cusps after culturing under biaxial stretch for 14 days. The contents of collagen and glycosaminoglycans were determined using standard biochemical assays and compared with fresh controls. Strain fields in static cusps were more uniform than those in stretched cusps, which indicated degradation of the ECM fibers. The glycosaminoglycan content was significantly elevated in the static control as compared to fresh or stretched cusps, but no difference was observed in collagen content among the groups. The strain profile of freshly isolated fibrosa vs. ventricularis and left, right, and noncoronary cusps were also determined by Digital Image Correlation technique. Distinct strain patterns were observed under stretch on fibrosa and ventricularis sides and among the three cusps. This work highlights the critical role of the anisotropic ECM structure for proper functions of native aortic valves and the beneficial effects of biaxial stretch for maintenance of the native ECM structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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

  15. 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

  16. 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...

  17. 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.

  18. Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

    Science.gov (United States)

    Tanaka, Leonardo Y; Laurindo, Francisco R M

    2017-08-01

    Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases. Copyright © 2017 Elsevier Inc. All

  19. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in gingival crevicular fluid during orthodontic tooth movement.

    NARCIS (Netherlands)

    Bildt, M.M.; Bloemen, M.; Kuijpers-Jagtman, A.M.; Hoff, J.W. Von den

    2009-01-01

    Orthodontic tooth movement requires extensive re-modelling of the periodontium. Matrix metalloproteinases (MMPs) degrade the extracellular matrix during re-modelling, while their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was to investigate

  20. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in gingival crevicular fluid during orthodontic tooth movement

    NARCIS (Netherlands)

    Bildt, Miriam; Bloemen, M; Kuijpers-Jagtman, A.M.; Von Den Hoff, Johannes W

    2009-01-01

    Orthodontic tooth movement requires extensive re-modelling of the periodontium. Matrix metalloproteinases (MMPs) degrade the extracellular matrix during re-modelling, while their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was to investigate

  1. The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis.

    Science.gov (United States)

    Yang, Mei; Jiang, Chunfan; Chen, Hua; Nian, Yan; Bai, Zhimiao; Ha, Chunfang

    2015-08-20

    Endometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration. We performed primary culture of EECs and investigated the expression of OPN and MMP-9 in EECs regulated by 17beta-estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and to explore the corresponding change in MMP-9 expression. Real-time RT-PCR, western blot analysis and flow cytometry were used to determine the expression levels of OPN and MMP-9. Gelatin zymography was performed to observe the enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch assays were performed to investigate the migration ability of EECs. The expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those in EECs from patients with endometriosis (EEECs). The expression levels of OPN and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA interference. Active MMP-9 expression increased with E2 treatment and decreased with siRNA treatment in EEECs compared with the same treatments in NEECs. The migratory abilities of EEECs were enhanced after cells were treated with E2; in contrast, these abilities were reduced by siRNA interference. In NEECs, active MMP-9 and cellular migration abilities were only minimally influenced by E2 and siRNA treatment. The present study suggests that the up-regulation of MMP-9 via activation of OPN induced by estrogen may correlate with the migration of endometrial epithelial cells in patients with endometriosis.

  2. PHAGOCYTOSIS AND REMODELING OF COLLAGEN MATRICES

    OpenAIRE

    Abraham, Leah C.; Dice, J Fred.; Lee, Kyongbum; Kaplan, David L.

    2007-01-01

    The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lun...

  3. 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.

  4. Matrix metalloproteinases in acute coronary syndromes: current perspectives.

    Science.gov (United States)

    Kampoli, Anna-Maria; Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Androulakis, Emmanuel; Tsiamis, Eleftherios; Latsios, George; Stefanadis, Christodoulos

    2012-01-01

    Matrix metalloproteinases (MMPs) are a family of zinc metallo-endopeptidases secreted by cells and are responsible for much of the turnover of matrix components. Several studies have shown that MMPs are involved in all stages of the atherosclerotic process, from the initial lesion to plaque rupture. Recent evidence suggests that MMP activity may facilitate atherosclerosis, plaque destabilization, and platelet aggregation. In the heart, matrix metalloproteinases participate in vascular remodeling, plaque instability, and ventricular remodelling after cardiac injury. The aim of the present article is to review the structure, function, regulation of MMPs and to discuss their potential role in the pathogenesis of acute coronary syndromes, as well as their contribution and usefullness in the setting of the disease.

  5. [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.

  6. Lysyl oxidases regulate fibrillar collagen remodelling in idiopathic pulmonary fibrosis

    NARCIS (Netherlands)

    Tjin, Gavin; White, Eric S; Faiz, Alen; Sicard, Delphine; Tschumperlin, Daniel J; Mahar, Annabelle; Kable, Eleanor P W; Burgess, Janette K

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with feweffective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linkingmediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease

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

    Science.gov (United States)

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

    2015-01-01

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

  8. Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling

    Science.gov (United States)

    Carpio, Lomeli R.; Bradley, Elizabeth W.; McGee-Lawrence, Meghan E.; Weivoda, Megan M.; Poston, Daniel D.; Dudakovic, Amel; Xu, Ming; Tchkonia, Tamar; Kirkland, James L.; van Wijnen, Andre J.; Oursler, Merry Jo; Westendorf, Jennifer J.

    2017-01-01

    Histone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, each of these drugs inhibits multiple HDACs and has detrimental effects on the skeleton. To better understand how HDAC inhibitors affect endochondral bone formation, we conditionally deleted one of their targets, Hdac3, pre- and postnatally in type II collagen α1 (Col2α1)–expressing chondrocytes. Embryonic deletion was lethal, but postnatal deletion of Hdac3 delayed secondary ossification center formation, altered maturation of growth plate chondrocytes, and increased osteoclast activity in the primary spongiosa. HDAC3-deficient chondrocytes exhibited increased expression of cytokine and matrix-degrading genes (Il-6, Mmp3, Mmp13, and Saa3) and a reduced abundance of genes related to extracellular matrix production, bone development, and ossification (Acan, Col2a1, Ihh, and Col10a1). Histone acetylation increased at and near genes that had increased expression. The acetylation and activation of nuclear factor κB (NF-κB) were also increased in HDAC3-deficient chondrocytes. Increased cytokine signaling promoted autocrine activation of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and NF-κB pathways to suppress chondrocyte maturation, as well as paracrine activation of osteoclasts and bone resorption. Blockade of interleukin-6 (IL-6)–JAK–STAT signaling, NF-κB signaling, and bromodomain extraterminal proteins, which recognize acetylated lysines and promote transcriptional elongation, significantly reduced Il-6 and Mmp13 expression in HDAC3-deficient chondrocytes and secondary activation in osteoclasts. The JAK inhibitor ruxolitinib also reduced osteoclast activity in Hdac3 conditional knockout mice. Thus, HDAC3 controls the temporal and spatial expression of tissue-remodeling genes and inflammatory responses in chondrocytes to ensure proper endochondral ossification during development. PMID

  9. 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.

  10. Matrix Metalloproteinase Enzyme Family

    Directory of Open Access Journals (Sweden)

    Ozlem Goruroglu Ozturk

    2013-04-01

    Full Text Available Matrix metalloproteinases play an important role in many biological processes such as embriogenesis, tissue remodeling, wound healing, and angiogenesis, and in some pathological conditions such as atherosclerosis, arthritis and cancer. Currently, 24 genes have been identified in humans that encode different groups of matrix metalloproteinase enzymes. This review discuss the members of the matrix metalloproteinase family and their substrate specificity, structure, function and the regulation of their enzyme activity by tissue inhibitors. [Archives Medical Review Journal 2013; 22(2.000: 209-220

  11. New aspects of vascular remodelling: the involvement of all vascular cell types.

    Science.gov (United States)

    McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

    2005-07-01

    Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

  12. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kaoru Miyazaki

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

  15. 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

  16. 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.

  17. 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...

  18. 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 ...

  19. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Directory of Open Access Journals (Sweden)

    Toshifumi Tezuka

    Full Text Available Plasminogen activator inhibitor (PAI-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp. IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

  20. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Science.gov (United States)

    Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

    2015-01-01

    Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

  1. Bone remodelling: its local regulation and the emergence of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2008-10-01

    Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

  2. Concomitant lack of MMP9 and uPA disturbs physiological tissue remodeling

    DEFF Research Database (Denmark)

    Lund, Ida K; Nielsen, Boye S; Almholt, Kasper

    2011-01-01

    Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9, gelatinase B) have separately been recognized to play important roles in various tissue remodeling processes. In this study, we demonstrate that deficiency for MMP9 in combination with ablation of either uPA- or tiss......PAR, when MMP9 is absent. Notably, compensatory upregulation of uPA activity was seen in wounds from MMP9-deficient mice. Taken together, these studies reveal essential functional dependency between MMP9 and uPA during gestation and tissue repair.......Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9, gelatinase B) have separately been recognized to play important roles in various tissue remodeling processes. In this study, we demonstrate that deficiency for MMP9 in combination with ablation of either uPA- or tissue...

  3. 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.

  4. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha

    2010-01-01

    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via...

  5. Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

    NARCIS (Netherlands)

    Liu, Gang; Cooley, Marion A; Jarnicki, Andrew G; Hsu, Alan C-Y; Nair, Prema M; Haw, Tatt Jhong; Fricker, Michael; Gellatly, Shaan L; Kim, Richard Y; Inman, Mark D; Tjin, Gavin; Wark, Peter A B; Walker, Marjorie M; Horvat, Jay C; Oliver, Brian G; Argraves, W Scott; Knight, Darryl A; Burgess, Janette K; Hansbro, Philip M

    2016-01-01

    Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM protein

  6. A supra-cellular model for coupling of bone resorption to formation during remodeling

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L

    2014-01-01

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the ost......The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released...... by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow...... and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors...

  7. Level of matrix metalloproteinase-9 and myocardium remodeling in patients with acute postinfarction aneurism of left ventricle

    Directory of Open Access Journals (Sweden)

    V. D. Syvolap

    2013-12-01

    Full Text Available 67 patients with diagnosis: Q-wave myocardial infarction – were examined. Level of matrix metalloproteinase-9, structural and functional indexes of myocardium remodeling were studied in patients with acute postinfarction aneurism of left ventricle. Early predictors of left ventricle aneurism formation were revealed in patients with acute Q-wave myocardial infarction. Abstract Background. Problem of acute myocardial infarction till nowadays remains relevant, because it’s one of the leading causes of mortality, morbidity and disability in most developed countries. Severity of postinfarction remodeling is a factor that determines the degree of myocardial dysfunction and prognosis of survival. During the first few days after the onset of AMI disproportionately thinned and stretched infarcted area, which is no longer able to resist to intraventricular pressure, which subsequently leads to an expansion of a heart attack until the formation of an aneurysm or heart failure. In this case, the structural and functional changes in the heart muscle affects both the affected and intact areas of the myocardium , marked by the passage of the phase of adaptive and maladaptive processes. Mechanisms of postinfarction remodeling caused by the interaction of cell as well as extracellular factors, starting immediately after coronary artery occlusion with the normal degradation of the extracellular matrix , migration of inflammatory cells to the site of damage and induction of biologically active peptides. In recent studies there was a high expression of MMP -9 in patients with acute coronary syndrome, showing the value of its serum concentration as a marker of inflammation, a predictor of restenosis and cardiovascular mortality in patients with coronary heart disease. This gives reason to explore the prognostic value of early detection of the level of MMP -9 in myocardial infarction as a marker of adverse postinfarction remodeling. Methods. Sixty seven patients

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

    Science.gov (United States)

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

    2017-06-01

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

  9. Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction.

    Science.gov (United States)

    Jenkins, Molly H; Alrowaished, Sarah S; Goody, Michelle F; Crawford, Bryan D; Henry, Clarissa A

    2016-01-01

    Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition. We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture. These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.

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

    Directory of Open Access Journals (Sweden)

    Ahmed Walid A. Morad

    2015-09-01

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

  11. Human Endometrial CD98 Is Essential for Blastocyst Adhesion

    Science.gov (United States)

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

    2010-01-01

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

  12. Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?

    Science.gov (United States)

    Agarwal, Puneet; Agarwal, Renu

    2018-06-14

    Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.

  13. Extrauterine Low-Grade Endometrial Stromal Sarcoma

    Directory of Open Access Journals (Sweden)

    Yu-Ju Chen

    2005-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-15

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

  15. 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

  16. 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 ...

  17. 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 ...

  18. Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities.

    Science.gov (United States)

    Gajarsa, Jason J; Kloner, Robert A

    2011-01-01

    As more patients survive myocardial infarctions, the incidence of heart failure increases. After an infarction, the human heart undergoes a series of structural changes, which are governed by cellular and molecular mechanisms in a pathological metamorphosis termed "remodeling." This review will discuss the current developments in our understanding of these molecular and cellular events in remodeling and the various pharmacological, cellular and device therapies used to treat, and potentially retard, this condition. Specifically, this paper will examine the neurohormonal activity of the renin-angiotensin-aldosterone axis and its molecular effects on the heart. The emerging understanding of the extra-cellular matrix and the various active molecules within it, such as the matrix metalloproteinases, elicits new appreciation for their role in cardiac remodeling and as possible future therapeutic targets. Cell therapy with stem cells is another recent therapy with great potential in improving post-infarcted hearts. Lastly, the cellular and molecular effects of left ventricular assist devices on remodeling will be reviewed. Our increasing knowledge of the cellular and molecular mechanisms underlying cardiac remodeling enables us not only to better understand how our more successful therapies, like angiotensin-converting enzyme inhibitors, work, but also to explore new therapies of the future.

  19. 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...

  20. Multifaceted role of matrix metalloproteinases (MMPs)

    OpenAIRE

    Singh, Divya; Srivastava, Sanjeev K.; Chaudhuri, Tapas K.; Upadhyay, Ghanshyam

    2015-01-01

    Matrix metalloproteinases (MMPs), a large family of calcium-dependent zinc-containing endopeptidases, are involved in the tissue remodeling and degradation of the extracellular matrix. MMPs are widely distributed in the brain and regulate various processes including microglial activation, inflammation, dopaminergic apoptosis, blood-brain barrier disruption, and modulation of ?-synuclein pathology. High expression of MMPs is well documented in various neurological disorders including Parkinson...

  1. CELLULAR MECHANISMS OF BONE REMODELING DUE TO EXTERNAL OVERLOAD AND UNDER CONDITIONS OF TITAN IMPLANT OSSEOINTEGRATION

    Directory of Open Access Journals (Sweden)

    Gaifullin N.M.

    2016-04-01

    Full Text Available The goal of article concludes to describe the remodeling of the femur, caused by two processes: the increased strain on supporting tissue as a result of anterior cruciate ligament transection and stimulation by installation of endosseous titanium implants with a porous bioactive coating. The process is traced through 4, 8 and 12 weeks in 28 adult Wistar rats. To characterize the bone remodeling the classical methods of histology and morphometry as well as immune histochemistry to reveal osteonectin, tartrate-resistant acid phosphatase, endothelial marker СD31, matrix metalloproteinases MMP-2, MMP-9, and its tissue inhibitor TIMP-1, were used with necessary morphometrics. The study showed for bone remodelling caused by implants with a porous bioactive coating, to be superior to a similar process under conditions of overload on the bone after transection of the anterior cruciate ligament by its intensity and dynamics. This indicates a high osteoinductive effect of bioactive coating that allows not only to achieve full osseointegration, but also to stimulate a process of intensive remodeling of adjacent cancellous bone. The cooperative participation of cell populations as osteoblasts/osteocytes, osteoclasts, and endothelial cells with characteristic parallel intensive expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitor TIMP-1, used to be main characteristics of bone remodeling in these conditions.

  2. 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)

  3. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  4. EMMPRIN is secreted by human uterine epithelial cells in microvesicles and stimulates metalloproteinase production by human uterine fibroblast cells.

    Science.gov (United States)

    Braundmeier, A G; Dayger, C A; Mehrotra, P; Belton, R J; Nowak, R A

    2012-12-01

    Endometrial remodeling is a physiological process involved in the gynecological disease, endometriosis. Tissue remodeling is directed by uterine fibroblast production of matrix metalloproteinases (MMPs). Several MMPs are regulated directly by the protein extracellular matrix metalloproteinase inducer (EMMPRIN) and also by proinflammatory cytokines such as interleukin (IL)1-α/β. We hypothesized that human uterine epithelial cells (HESs) secrete intact EMMPRIN to stimulate MMPs. Microvesicles from HES cell-conditioned medium (CM) expressed intact EMMPRIN protein. Treatment of HES cells with estradiol or phorbyl 12-myristate-13-acetate increased the release of EMMPRIN-containing microvesicles. The HES CM stimulated MMP-1, -2, and -3 messenger RNA levels in human uterine fibroblasts (HUFs) and EMMPRIN immunodepletion from HES-cell concentrated CM reduced MMP stimulation (P EMMPRIN, in response to ovarian hormones, proinflammatory cytokines as well as activation of protein kinase C.

  5. Residency and Activation of Myeloid Cells During Remodeling of the Prepartum Murine Cervix1

    Science.gov (United States)

    Payne, Kimberly J.; Clyde, Lindsey A.; Weldon, Abby J.; Milford, Terry-Ann; Yellon, Steven M.

    2012-01-01

    ABSTRACT Remodeling of the cervix is a critical early component of parturition and resembles an inflammatory process. Infiltration and activation of myeloid immune cells along with production of proinflammatory mediators and proteolytic enzymes are hypothesized to regulate cervical remodeling as pregnancy nears term. The present study standardized an approach to assess resident populations of immune cells and phenotypic markers of functional activities related to the mechanism of extracellular matrix degradation in the cervix in preparation for birth. Analysis of cells from the dispersed cervix of mice that were nonpregnant or pregnant (Days 15 and 18 postbreeding) by multicolor flow cytometry indicated increased total cell numbers with pregnancy as well as increased numbers of macrophages, the predominant myeloid cell, by Day 18, the day before birth. The number of activated macrophages involved in matrix metalloproteinase induction (CD147) and signaling for matrix adhesion (CD169) significantly increased by the day before birth. Expression of the adhesion markers CD54 and CD11b by macrophages decreased in the cervix by Day 18 versus that on Day 15 or in nonpregnant mice. The census of cells that expressed the migration marker CD62L was unaffected by pregnancy. The data suggest that remodeling of the cervix at term in mice is associated with recruitment and selective activation of macrophages that promote extracellular matrix degradation. Indices of immigration and activities by macrophages may thus serve as markers for local immune cell activity that is critical for ripening of the cervix in the final common mechanism for parturition at term. PMID:22914314

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

    Science.gov (United States)

    Kato, Kiyoko; Takao, Tomoka; Kuboyama, Ayumi; Tanaka, Yoshihiro; Ohgami, Tatsuhiro; Yamaguchi, Shinichiro; Adachi, Sawako; Yoneda, Tomoko; Ueoka, Yousuke; Kato, Keiji; Hayashi, Shinichi; Asanoma, Kazuo; Wake, Norio

    2010-01-01

    Cancer stem-like cell subpopulations, referred to as “side-population” (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and, uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, α-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into α-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage. PMID:20008133

  7. Gelatinase (MMP-2 and -9 expression profiles during gestation in the bovine endometrium

    Directory of Open Access Journals (Sweden)

    Sato Takashi

    2008-12-01

    Full Text Available Abstract Background Various molecules participate in implantation and maintaining endometrial function during gestation. The remodeling of endometrial matrices is a necessary process in the coordination of gestational progress. Matrix-metalloproteinases (MMPs like gelatinases (MMP-2 and -9 and collagenase (MMP-1 are considered to play important roles in this process. We examined MMP-2 and -9 expression using zymography, in situ hybridization, real-time PCR, and microarray analysis to clarify their roles in the bovine endometrium during gestation. Methods Endometria, placentomes, and fetal membranes were collected from Japanese black cows that were killed on day 15 to 252 of gestation or during their estrous cycle. The gene expression of MMP-related molecules (mainly MMP-2 and -9 was examined using a custom-made microarray, real-time RT-PCR, and in-situ hybridization. Gelatinase activity was detected by zymography and film in situ zymography. Results Both gelatinases were expressed in the endometrium and fetal tissues throughout gestation. MMP-2 gene expression declined with the progress of gestation, but its intensity was maintained at a high level during the peri-implantation period and increased in late gestation. The expression level of MMP-9 was stably maintained, but was relatively low compared to that of MMP-2. These gene expression patterns matched those detected by zymography for the proteins. Microarray analysis suggested that the functions of MMP-2 during implantation and the last part of gestation are closely related with those of other molecules such as tissue inhibitors of metalloproteinase (TIMP-2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS 1, membrane type 1 (MT1-MMP, and extracellular matrix metalloproteinase inducer (EMMPRIN. Conclusion We detected MMP-2 and -9 gene expression in the bovine endometrium and placentome throughout gestation. These data suggest that MMP-2 is one of the main endometrial

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Disorganized collagen scaffold interferes with fibroblast mediated deposition of organized extracellular matrix in vitro.

    Science.gov (United States)

    Saeidi, Nima; Guo, Xiaoqing; Hutcheon, Audrey E K; Sander, Edward A; Bale, Shyam Sundar; Melotti, Suzanna A; Zieske, James D; Trinkaus-Randall, Vickery; Ruberti, Jeffrey W

    2012-10-01

    Many tissue engineering applications require the remodeling of a degradable scaffold either in vitro or in situ. Although inefficient remodeling or failure to fully remodel the temporary matrix can result in a poor clinical outcome, very few investigations have examined in detail, the interaction of regenerative cells with temporary scaffoldings. In a recent series of investigations, randomly oriented collagen gels were directly implanted into human corneal pockets and followed for 24 months. The resulting remodeling response exhibited a high degree of variability which likely reflects differing regenerative/synthetic capacity across patients. Given this variability, we hypothesize that a disorganized, degradable provisional scaffold could be disruptive to a uniform, organized reconstruction of stromal matrix. In this investigation, two established corneal stroma tissue engineering culture systems (collagen scaffold-based and scaffold-free) were compared to determine if the presence of the disorganized collagen gel influenced matrix production and organizational control exerted by primary human corneal fibroblast cells (PHCFCs). PHCFCs were cultured on thin disorganized reconstituted collagen substrate (RCS--five donors: average age 34.4) or on a bare polycarbonate membrane (five donors: average age 32.4 controls). The organization and morphology of the two culture systems were compared over the long-term at 4, 8, and 11/12 weeks. Construct thickness and extracellular matrix organization/alignment was tracked optically with bright field and differential interference contrast (DIC) microscopy. The details of cell/matrix morphology and cell/matrix interaction were examined with standard transmission, cuprolinic blue and quick-freeze/deep-etch electron microscopy. Both the scaffold-free and the collagen-based scaffold cultures produced organized arrays of collagen fibrils. However, at all time points, the amount of organized cell-derived matrix in the scaffold

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

    Directory of Open Access Journals (Sweden)

    Longwen Chen

    2014-01-01

    Full Text Available The 2001 Bethesda system recommends further classifying atypical glandular cells (AGCs as either endocervical or endometrial origin. Numerous studies have investigated the clinical significance of AGC. In this study, we investigated the incidence of clinically significant lesions among women with liquid-based Papanicolaou cervicovaginal (Pap interpretations of atypical endometrial cells (AEMs or AGC favor endometrial origin (AGC-EM. More importantly, we correlated patients of AEM or AGC-EM with their clinical presentations to determine if AEM/AGC-EM combined with abnormal vaginal bleeding is associated with a higher incidence of significant endometrial pathology. All liquid-based Pap tests with an interpretation of AEM and AGC-EM from July, 2004 through June, 2009 were retrieved from the database. Women with an interpretation of atypical endocervical cells, AGC, favor endocervical origin or AGC, favor neoplastic were not included in the study. The most severe subsequent histologic diagnoses were recorded for each patient. During this 5-year period, we accessioned 332,470 Pap tests of which 169 (0.05% were interpreted as either AEM or AGC-EM. Of the 169 patients, 133 had histologic follow-up within the health care system. The patients ranged in age from 21 to 71 years old (mean 49.7. On follow-up histology, 27 (20.3% had neoplastic/preneoplastic uterine lesions. Among them, 20 patients were diagnosed with adenocarcinoma (18 endometrial, 1 endocervical, and 1 metastatic colorectal, 3 with atypical endometrial hyperplasia, and 4 with endometrial hyperplasia without atypia. All patients with significant endometrial pathology, except one, were over 40 years old, and 22 of 25 patients reported abnormal vaginal bleeding at the time of endometrial biopsy or curettage. This study represents a large series of women with liquid-based Pap test interpretations of AEM and AGC-EM with clinical follow-up. Significant preneoplastic or neoplastic endometrial

  15. 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...

  16. 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...

  17. A novel assay for extracellular matrix remodeling associated with liver fibrosis

    DEFF Research Database (Denmark)

    Barascuk, N; Veidal, S S; Larsen, L

    2010-01-01

    Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation.......Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation....

  18. 25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

    International Nuclear Information System (INIS)

    Ichikawa, Tomohiro; Sugiura, Hisatoshi; Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki; Ichinose, Masakazu

    2013-01-01

    Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P 1 production (P 1 release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway

  19. Redundancy of IL-1 Isoform Signaling and Its Implications for Arterial Remodeling.

    Directory of Open Access Journals (Sweden)

    Marina Beltrami-Moreira

    Full Text Available Mice deficient in IL-1 receptor 1 (hence unresponsive to both IL-1 isoforms α and β have impaired expansive arterial remodeling due to diminished expression of matrix-degrading enzymes, especially MMP-3. Emergence of IL-1 as a target in cardiovascular disease prompted the investigation of the redundancy of IL-1α and IL-1β in the induction of MMP-3 and other matrix-remodeling enzymes in human cells.Human primary vascular smooth muscle cells (VSMCs and carotid endarterectomy specimens were stimulated with equimolar concentrations of IL-1α or IL-1β and analyzed protease expression by immunoblot and ELISA. Either IL-1α or IL-1β increased the expression of pro-MMP-3 in VSMCs, facilitated VSMC migration through Matrigel, and induced MMP-3 production in specimens from atheromatous plaques. VSMCs also secreted MMP-1 and Cathepsin S (CatS upon stimulation with IL-1α or IL-1β. IL-1 isoforms similarly increased MMP-1 and MMP-9 expression in carotid endarterectomy specimens. We examined the expression of MMP-3 and IL-1 isoforms by immunostaining of carotid atheromata, calculated the % positive areas, and tested associations by linear regression. MMP-3 colocalized with IL-1 isoforms in atheromata. MMP-3+ area in plaques positively associated with IL-1α+ (R2 = 0.61, P<0.001 and with IL-1β + areas (R2 = 0.68, P<0.001. MMP-3+ area within atheroma also associated with CD68+ area, but not with α-smooth muscle actin area.Either IL-1α or IL-1β can induce the expression of enzymes implicated in remodeling of the arterial extracellular matrix, and facilitate human VSMC migration in vitro. Human atheromata contain both IL-1 isoforms in association with immunoreactive MMP-3. This redundancy of IL-1 isoforms suggests that selective blocking of one IL-1 isoform should not impair expansive arterial remodeling, a finding with important clinical implications for therapeutic targeting of IL-1 in atherosclerosis.

  20. Functional dilatation and medial remodeling of the renal artery in response to chronic increased blood flow.

    Science.gov (United States)

    Roan, Jun-Neng; Yeh, Chin-Yi; Chiu, Wen-Cheng; Lee, Chou-Hwei; Chang, Shih-Wei; Jiangshieh, Ya-Fen; Tsai, Yu-Chuan; Lam, Chen-Fuh

    2011-01-01

    Renal blood flow (RBF) is tightly regulated by several intrinsic pathways in maintaining optimal kidney blood supply. Using a rat model of aortocaval (AC) fistula, we investigated remodeling of the renal artery following prolonged increased blood flow. An AC fistula was created in the infrarenal aorta of anesthetized rats, and changes of blood flow in the renal artery were assessed using an ultrasonic flow probe. Morphological changes and expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 in the remodeled renal artery were analyzed. Blood flow in the renal artery increased immediately after creation of AC fistula, but normal RBF was restored 8 weeks later. The renal artery dilated significantly 8 weeks after operation. Expression of endothelial nitric oxide synthase and matrix metalloproteinase-2 was upregulated shortly after blood flow increase, and returned to baseline levels after 3 weeks. Histological sections showed luminal dilatation with medial thickening and endothelial cell-to-smooth muscle cell attachments in the remodeled renal artery. Increased RBF was accommodated by functional dilatation and remodeling in the medial layer of the renal artery in order to restore normal blood flow. Our results provide important mechanistic insight into the intrinsic regulation of the renal artery in response to increased RBF. Copyright © 2011 S. Karger AG, Basel.

  1. Matrix metalloproteinases in exercise and obesity

    OpenAIRE

    Jaoude, Jonathan; Koh, Yunsuk

    2016-01-01

    Jonathan Jaoude,1 Yunsuk Koh2 1Department of Biology, 2Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA Abstract: Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endoproteinases that have the ability to break down extracellular matrix. The large range of MMPs’ functions widens their spectrum of potential role as activators or inhibitors in tissue remodeling, cardiovascular diseases, and obesity. In particular, MMP-1, -2, and ...

  2. Left ventricular remodelling in chronic primary mitral regurgitation: implications for medical therapy.

    Science.gov (United States)

    McCutcheon, Keir; Manga, Pravin

    Surgical repair or replacement of the mitral valve is currently the only recommended therapy for severe primary mitral regurgitation. The chronic elevation of wall stress caused by the resulting volume overload leads to structural remodelling of the muscular, vascular and extracellular matrix components of the myocardium. These changes are initially compensatory but in the long term have detrimental effects, which ultimately result in heart failure. Understanding the changes that occur in the myocardium due to volume overload at the molecular and cellular level may lead to medical interventions, which potentially could delay or prevent the adverse left ventricular remodelling associated with primary mitral regurgitation. The pathophysiological changes involved in left ventricular remodelling in response to chronic primary mitral regurgitation and the evidence for potential medical therapy, in particular beta-adrenergic blockers, are the focus of this review.

  3. 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 ...

  4. Integration of concepts: cardiac extracellular matrix remodeling after myocardial infarction

    NARCIS (Netherlands)

    Cleutjens, Jack P. M.; Creemers, Esther E. J. M.

    2002-01-01

    The cardiac extracellular matrix consists of a three-dimensional structural network of interstitial collagens to which other matrix components are attached. The main physiological functions of this network are to retain tissue integrity and cardiac pump function. Collagen deposition is controlled

  5. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms.

    Science.gov (United States)

    Stenmark, Kurt R; Fagan, Karen A; Frid, Maria G

    2006-09-29

    Chronic hypoxic exposure induces changes in the structure of pulmonary arteries, as well as in the biochemical and functional phenotypes of each of the vascular cell types, from the hilum of the lung to the most peripheral vessels in the alveolar wall. The magnitude and the specific profile of the changes depend on the species, sex, and the developmental stage at which the exposure to hypoxia occurred. Further, hypoxia-induced changes are site specific, such that the remodeling process in the large vessels differs from that in the smallest vessels. The cellular and molecular mechanisms vary and depend on the cellular composition of vessels at particular sites along the longitudinal axis of the pulmonary vasculature, as well as on local environmental factors. Each of the resident vascular cell types (ie, endothelial, smooth muscle, adventitial fibroblast) undergo site- and time-dependent alterations in proliferation, matrix protein production, expression of growth factors, cytokines, and receptors, and each resident cell type plays a specific role in the overall remodeling response. In addition, hypoxic exposure induces an inflammatory response within the vessel wall, and the recruited circulating progenitor cells contribute significantly to the structural remodeling and persistent vasoconstriction of the pulmonary circulation. The possibility exists that the lung or lung vessels also contain resident progenitor cells that participate in the remodeling process. Thus the hypoxia-induced remodeling of the pulmonary circulation is a highly complex process where numerous interactive events must be taken into account as we search for newer, more effective therapeutic interventions. This review provides perspectives on each of the aforementioned areas.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

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

  10. Adjuvant radiotherapy for stage I endometrial cancer.

    Science.gov (United States)

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

    2007-04-18

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

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

    Directory of Open Access Journals (Sweden)

    Arthur-Quan Tran

    2017-01-01

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

  12. Serum markers of the extracellular matrix remodelling reflect antifibrotic therapy in bile-duct ligated rats.

    Directory of Open Access Journals (Sweden)

    Robert eSchierwagen

    2013-07-01

    Full Text Available BackgroundProgression of liver fibrosis is characterized by synthesis and degradation of extracellular matrix (ECM. Matrix-metalloproteinases (MMP cleave collagen fibers at a specific site and thereby generate soluble fragments of ECM (neo-epitopes. The levels of these neo-epitopes might reflect the stage of liver fibrosis and may allow monitoring of anti-fibrotic therapies. Here we analyzed these neo-epitopes as read-out for a liver directed therapy with statins.MethodsBile duct ligation (BDL was performed on wildtype rats, which received atorvastatin (15mg/kg*d for one week starting at one, two, three, four and five weeks after BDL (T1-T5, while controls remained untreated. Hepatic fibrosis was analyzed by immunohistochemistry and hepatic hydroxyproline content. TGFβ levels were measured by RT-PCR. Proteolytic activity of MMP-2 was examined by zymography. Levels of degradation MMP driven type I, III, IV and VI collagen degradation (C1M, C3M, C4M and C6M and type III and IV collagen formation (PRO-C3 and P4NP7S markers were assessed by specific ELISAs in serum probes.ResultsSerum markers of ECM neo-epitopes reflected significantly the deposition of ECM in the liver and were able to distinguish between early (T1-T3 and severe fibrosis (T4-T5. Statin treatment to the fibrotic livers resulted in reduction of neo-epitope markers, especially when therapy was started in the stage of severe fibrosis (T4-T5. Furthermore, these markers correlated with hepatic expression of profibrotic cytokines TGFβ1 and TGFβ2. Formation markers of type III and IV collagen (PRO-C3 and P4NP7S and degradation markers C4M and C6M correlated significantly with MMP-2 activity in rats with severe fibrosis. ConclusionDetermination of ECM remodelling turnover markers in serum allowed a distinction between mild and severe fibrosis. With respect to statin therapy, the markers may serve as read-out for efficacy of anti-fibrotic treatment.

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

    Science.gov (United States)

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

    2017-11-13

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

  14. Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fu [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Chambon, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104, INSERM U596, ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg (France); Tellides, George [Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT (United States); Kong, Wei [Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing (China); Zhang, Xiaoming, E-mail: rmygxgwk@163.com [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Li, Wei [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China)

    2014-11-07

    Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

  15. 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%.

  16. Altered protein expression in serum from endometrial hyperplasia and carcinoma patients

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    Cong Qing

    2011-04-01

    Full Text Available Abstract Background Endometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions. Methods In this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™, and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database. Results In total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein. Conclusions The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.

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

    Science.gov (United States)

    Bantysh, B B; Paukov, v S; Kogan, E A

    2012-01-01

    The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.

  18. Increased endometrial thickness in women with hypertension.

    Science.gov (United States)

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

    2000-09-01

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

  19. Repeated short climatic change affects the epidermal differentiation program and leads to matrix remodeling in a human organotypic skin model.

    Science.gov (United States)

    Boutrand, Laetitia-Barbollat; Thépot, Amélie; Muther, Charlotte; Boher, Aurélie; Robic, Julie; Guéré, Christelle; Vié, Katell; Damour, Odile; Lamartine, Jérôme

    2017-01-01

    Human skin is subject to frequent changes in ambient temperature and humidity and needs to cope with these environmental modifications. To decipher the molecular response of human skin to repeated climatic change, a versatile model of skin equivalent subject to "hot-wet" (40°C, 80% relative humidity [RH]) or "cold-dry" (10°C, 40% RH) climatic stress repeated daily was used. To obtain an exhaustive view of the molecular mechanisms elicited by climatic change, large-scale gene expression DNA microarray analysis was performed and modulated function was determined by bioinformatic annotation. This analysis revealed several functions, including epidermal differentiation and extracellular matrix, impacted by repeated variations in climatic conditions. Some of these molecular changes were confirmed by histological examination and protein expression. Both treatments (hot-wet and cold-dry) reduced the expression of genes encoding collagens, laminin, and proteoglycans, suggesting a profound remodeling of the extracellular matrix. Strong induction of the entire family of late cornified envelope genes after cold-dry exposure, confirmed at protein level, was also observed. These changes correlated with an increase in epidermal differentiation markers such as corneodesmosin and a thickening of the stratum corneum, indicating possible implementation of defense mechanisms against dehydration. This study for the first time reveals the complex pattern of molecular response allowing adaption of human skin to repeated change in its climatic environment.

  20. The extracellular matrix deposited by asthmatic airway smooth muscle cells in a resting state reflects a healthy matrix

    NARCIS (Netherlands)

    Harkness, Louise; Ashton, Anthony; Burgess, Janette

    2015-01-01

    Introduction: The remodelled asthmatic airway features an altered extracellular matrix (ECM) & increased vasculature. Previous studies found asthmatic (A) airway smooth muscle cells (ASMCs) to deposit an ECM with enhanced bioactivity. These studies however investigated ECM deposited in the presence

  1. IKKα/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation.

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    Eleonora Olivotto

    Full Text Available BACKGROUND: The non-canonical NF-κB activating kinase IKKα, encoded by CHUK (conserved-helix-loop-helix-ubiquitous-kinase, has been reported to modulate pro- or anti- inflammatory responses, cellular survival and cellular differentiation. Here, we have investigated the mechanism of action of IKKα as a novel effector of human and murine chondrocyte extracellular matrix (ECM homeostasis and differentiation towards hypertrophy. METHODOLOGY/PRINCIPAL FINDINGS: IKKα expression was ablated in primary human osteoarthritic (OA chondrocytes and in immature murine articular chondrocytes (iMACs derived from IKKα(f/f:CreERT2 mice by retroviral-mediated stable shRNA transduction and Cre recombinase-dependent Lox P site recombination, respectively. MMP-10 was identified as a major target of IKKα in chondrocytes by mRNA profiling, quantitative RT-PCR analysis, immunohistochemistry and immunoblotting. ECM integrity, as assessed by type II collagen (COL2 deposition and the lack of MMP-dependent COL2 degradation products, was enhanced by IKKα ablation in mice. MMP-13 and total collagenase activities were significantly reduced, while TIMP-3 (tissue inhibitor of metalloproteinase-3 protein levels were enhanced in IKKα-deficient chondrocytes. IKKα deficiency suppressed chondrocyte differentiation, as shown by the quantitative inhibition of.Alizarin red staining and the reduced expression of multiple chondrocyte differentiation effectors, including Runx2, Col10a1 and Vegfa,. Importantly, the differentiation of IKKα-deficient chondrocytes was rescued by a kinase-dead IKKα protein mutant. CONCLUSIONS/SIGNIFICANCE: IKKα acts independent of its kinase activity to help drive chondrocyte differentiation towards a hypertrophic-like state. IKKα positively modulates ECM remodeling via multiple downstream targets (including MMP-10 and TIMP-3 at the mRNA and post-transcriptional levels, respectively to maintain maximal MMP-13 activity, which is required for ECM

  2. Monitoring of arterial wall remodelling in atherosclerotic rabbits with a magnetic resonance imaging contrast agent binding to matrix metalloproteinases

    Science.gov (United States)

    Hyafil, Fabien; Vucic, Esad; Cornily, Jean-Christophe; Sharma, Rahul; Amirbekian, Vardan; Blackwell, Francis; Lancelot, Eric; Corot, Claire; Fuster, Valentin; Galis, Zorina S.; Feldman, Laurent J.; Fayad, Zahi A.

    2011-01-01

    Aims P947 is a gadolinium-based magnetic resonance imaging (MRI) contrast agent with high affinity for several matrix metalloproteinases (MMPs) involved in arterial wall remodelling. We tested whether the intensity of enhancement detected in vivo in the arterial wall with P947 and MRI correlates with actual tissue MMP-related enzymatic activity measured in a rabbit atherosclerotic model subjected to dietary manipulations. Methods and results Aortas of 15 rabbits in which atherosclerotic lesions were induced by balloon angioplasty and 4 months of hypercholesterolaemic diet were imaged at ‘baseline’ with P947-enhanced MRI. Atherosclerotic rabbits were divided into three groups: five rabbits were sacrificed (‘baseline’ group); five rabbits continued to be fed a lipid-supplemented diet (‘high-fat’ group); and five rabbits were switched from atherogenic to a purified chow diet (‘low-fat’ group). Four months later, a second P947-enhanced MRI was acquired in the 10 remaining rabbits. A significantly lower signal was detected in the aortic wall of rabbits from the ‘low-fat’ group as compared with rabbits from the ‘high-fat’ group (21 ± 6 vs. 46 ± 3%, respectively; P = 0.04). Such differences were not detected with the contrast agent P1135, which lacks the MMP-specific peptide sequence. In addition, the intensity of aortic wall enhancement detected with MRI after injection of P947 strongly correlated with actual MMP-2 gelatinolytic activity measured in corresponding aortic segments using zymography (r = 0.87). Conclusion P947-enhanced MRI can distinguish dietary-induced variations in MMP-related enzymatic activity within plaques in an experimental atherosclerotic model, supporting its utility as a clinical imaging tool for in vivo detection of arterial wall remodelling. PMID:21118852

  3. Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert T; Liu, Xuhui

    2014-01-01

    extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

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

    Science.gov (United States)

    Sladkevicius, P; Installé, A; Van Den Bosch, T; Timmerman, D; Benacerraf, B; Jokubkiene, L; Di Legge, A; Votino, A; Zannoni, L; De Moor, B; De Cock, B; Van Calster, B; Valentin, L

    2018-02-01

    To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted

  5. 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

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

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    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.

  7. Hypoxia and cell cycle deregulation in endometrial carcinogenesis

    NARCIS (Netherlands)

    Horrée, N.

    2007-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  9. 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

  10. 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

  11. 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.

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

    Science.gov (United States)

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

    2016-02-01

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

  13. Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy.

    Science.gov (United States)

    Moustafa, Passant E; Abdelkader, Noha F; El Awdan, Sally A; El-Shabrawy, Osama A; Zaki, Hala F

    2018-04-27

    The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored

  14. 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, ...

  15. 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 ...

  16. 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.

  17. 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 ...

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Nalina S

    2017-07-01

    Full Text Available BACKGROUND Hysteroscopic-guided biopsy is the gold standard for endometrial sampling, but it carries risk of general anaesthesia, infection and perforation, whereas Pipelle does not require anaesthesia or cervical dilatation and it allows outpatient and painless endometrial sampling. The aim of the study is to determine the reliability and accuracy of Pipelle aspiration in acquiring an adequate and representative endometrial sample and to compare its histopathology with hysteroscopic-directed biopsy. MATERIALS AND METHODS A prospective observational comparative study evaluating the role of Pipelle aspiration as an outpatient procedure in endometrial sampling of perimenopausal women with AUB. 150 perimenopausal women with clinical diagnosis of abnormal uterine bleeding were selected from the Gynaecology OPD of IOG, Chennai, between October 2014 and September 2015. They were subjected to endometrial sampling by Pipelle followed by hysteroscopic-directed biopsy. The efficacy of Pipelle was determined by correlating the histopathological results obtained from it and the hysteroscopic-directed biopsy. RESULTS The histopathology of the endometrium obtained using Pipelle’s curette showed a sensitivity of 93%, specificity of 90% in the detection of abnormal findings with PPV of 88% and NPV of 94%. However, accuracy of Pipelle is found to be less in the diagnosis of polyps and submucous fibroids with accuracy of nearing 100% when using hysteroscopy. CONCLUSION Pipelle endometrial sampling is convenient, easy, painless and safe in obtaining an adequate sample for histopathology with high sensitivity and specificity for endometrial pathologies and endometrial carcinoma.

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

    Science.gov (United States)

    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.

  1. Beneficial Regulation of Matrix Metalloproteinases for Skin Health

    Directory of Open Access Journals (Sweden)

    Neena Philips

    2011-01-01

    Full Text Available Matrix metalloproteinases (MMPs are essential to the remodeling of the extracellular matrix. While their upregulation facilitates aging and cancer, they are essential to epidermal differentiation and the prevention of wound scars. The pharmaceutical industry is active in identifying products that inhibit MMPs to prevent or treat aging and cancer and products that stimulate MMPs to prevent epidermal hyperproliferative diseases and wound scars.

  2. Modeling the formation of cell-matrix adhesions on a single 3D matrix fiber.

    Science.gov (United States)

    Escribano, J; Sánchez, M T; García-Aznar, J M

    2015-11-07

    Cell-matrix adhesions are crucial in different biological processes like tissue morphogenesis, cell motility, and extracellular matrix remodeling. These interactions that link cell cytoskeleton and matrix fibers are built through protein clutches, generally known as adhesion complexes. The adhesion formation process has been deeply studied in two-dimensional (2D) cases; however, the knowledge is limited for three-dimensional (3D) cases. In this work, we simulate different local extracellular matrix properties in order to unravel the fundamental mechanisms that regulate the formation of cell-matrix adhesions in 3D. We aim to study the mechanical interaction of these biological structures through a three dimensional discrete approach, reproducing the transmission pattern force between the cytoskeleton and a single extracellular matrix fiber. This numerical model provides a discrete analysis of the proteins involved including spatial distribution, interaction between them, and study of the different phenomena, such as protein clutches unbinding or protein unfolding. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Identification, replication and characterization of epigenetic remodelling in the aging genome

    DEFF Research Database (Denmark)

    Li, Shuxia; Christiansen, Lene; Christensen, Kaare

    Background: Aging is a complex biological process that involves numerous changes at various levels through remodelling of multiple biological processes and regulatory mechanisms including epigenetics. Recent analysis of the DNA methylome has reported large numbers of epigenetic markers associated......, and by overwhelming age-related methylation in CpG island and demethylation at shore/shelf and open sea. Biological pathway analysis showed that age-dependent methylations were especially involved in cellular signalling activities while demethylations were particularly related to functions of the extracellular matrix....... Conclusion: Extensive epigenetic remodelling in the DNA methylome could be involved in the aging process. The identified age-methylated and demethylated sites displayed differential distribution patterns over genomic regions and were involved in biological pathways closely related to aging phenotypes and age...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-11-01

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

  5. 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

  6. 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

  7. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha

    2010-01-01

    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via...... their activity in the proteolytic degradation of extracellular macromolecules such as collagens, resulting in the generation of specific cleavage fragments. These neo-epitopes may be used as markers of fibrosis....

  8. Immunomodulatory Role of Adipose-Derived Stem Cells on Equine Endometriosis

    Directory of Open Access Journals (Sweden)

    Maria Elena Falomo

    2015-01-01

    Full Text Available Endometriosis is a degenerative process due to a chronic inflammatory damage leading to extracellular matrix components deposition and glandular fibrosis. It is known that mesenchymal stem cells secrete a wide range of bioactive molecules, some of them modulating the immune inflammatory response, and others providing regeneration and remodeling of injured tissue. We have performed in vitro experiments in order to analyze the capability of allogenic equine adipose-derived stem cells (ADSCs to infiltrate mares’ endometrial tissues and to stimulate the expression of cytokines and metallopeptidases. Differences in the biologic response to the exposure to ADSCs between pathological and healthy endometrial tissue have been identified. These results could challenge researchers to progress forward with future studies for the development of a biological therapy with a possible application in translational medicine.

  9. Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the endometrium of patients with repeated implantation failure after in vitro fertilization.

    Science.gov (United States)

    Turgut, A; Goruk, N Y; Tunc, S Y; Agaçayak, E; Alabalik, U; Yalinkaya, A; Gül, T

    2014-01-01

    To compare the immunohistochemical expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in repeated implantation failure (RIF) patients with normal fertile controls. The study group consisted of primary infertile patients with RIF and normal fertile controls between January 2011 and February 2013. Endometrial samples received at the luteal phase were exposed to immunohistochemical staining for EMMPRIN antibodies. EMMPRIN expression of endometrial glandular epithelial cells, stromal cells and vascular endothelial cells were evaluated. The main outcome measure was defined as immunohistochemical score with regard to the severity and extent of staining. The study group consisted of 26 primary infertile patients, whereas the control group consisted of 40 normal fertile controls. The fertile group was found to have stronger expression of EMMPRIN than the study group when endometrial glandular epithelial cells, stromal cells and vascular endothelial cells were evaluated with regards to the severity of staining (p EMMPRIN in the endometrial cells of the patients with RIF compared with fertile healthy controls. We suggest that reduced EMMPRIN expression in the human endometrium may lead to poor endometrial receptivity.

  10. 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.

  11. Mirror of the refined topological vertex from a matrix model

    CERN Document Server

    Eynard, B

    2011-01-01

    We find an explicit matrix model computing the refined topological vertex, starting from its representation in terms of plane partitions. We then find the spectral curve of that matrix model, and thus the mirror symmetry of the refined vertex. With the same method we also find a matrix model for the strip geometry, and we find its mirror curve. The fact that there is a matrix model shows that the refined topological string amplitudes also satisfy the remodeling the B-model construction.

  12. 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.

  13. 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 ...

  14. 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 ...

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression.

    Science.gov (United States)

    Wang, Feng-Wei; Cai, Mu-Yan; Mai, Shi-Juan; Chen, Jie-Wei; Bai, Hai-Yan; Li, Yan; Liao, Yi-Ji; Li, Chang-Peng; Tian, Xiao-Peng; Kung, Hsiang-Fu; Guan, Xin-Yuan; Xie, Dan

    2014-08-30

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.

  1. Periodontal Disease, Matrix Metalloproteinases and Chemically Modified Tetracyclines

    OpenAIRE

    Steinsvoll, Svein

    2011-01-01

    Matrix metalloproteinases (MMPs) are crucial in the degradation of the main components in the extracellular matrix and thereby play important roles in cell migration, wound healing and tissue remodelling. MMPs have pathogenic roles in arthritis, periodontitis, hepatitis, glomerulonephritis, atherosclerosis and cancer cell invasion. MMPs are activators of pro-inflammatory mediators that occur in latent forms, such as interleukin (IL)-1β, membrane-bound tumour necrosis factor (TNF) and dif...

  2. 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

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

    African Journals Online (AJOL)

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

  4. Assessment of Myocardial Remodeling Using an Elastin/Tropoelastin Specific Agent with High Field Magnetic Resonance Imaging (MRI)

    OpenAIRE

    Protti, Andrea; Lavin, Begoña; Dong, Xuebin; Lorrio, Silvia; Robinson, Simon; Onthank, David; Shah, Ajay M; Botnar, Rene M

    2015-01-01

    BACKGROUND: Well-defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction (MI) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin-specific contrast agent (Gd-...

  5. Mechanisms of action of sacubitril/valsartan on cardiac remodeling: a systems biology approach.

    Science.gov (United States)

    Iborra-Egea, Oriol; Gálvez-Montón, Carolina; Roura, Santiago; Perea-Gil, Isaac; Prat-Vidal, Cristina; Soler-Botija, Carolina; Bayes-Genis, Antoni

    2017-01-01

    Sacubitril/Valsartan, proved superiority over other conventional heart failure management treatments, but its mechanisms of action remains obscure. In this study, we sought to explore the mechanistic details for Sacubitril/Valsartan in heart failure and post-myocardial infarction remodeling, using an in silico, systems biology approach. Myocardial transcriptome obtained in response to myocardial infarction in swine was analyzed to address post-infarction ventricular remodeling. Swine transcriptome hits were mapped to their human equivalents using Reciprocal Best (blast) Hits, Gene Name Correspondence, and InParanoid database. Heart failure remodeling was studied using public data available in gene expression omnibus (accession GSE57345, subseries GSE57338), processed using the GEO2R tool. Using the Therapeutic Performance Mapping System technology, dedicated mathematical models trained to fit a set of molecular criteria, defining both pathologies and including all the information available on Sacubitril/Valsartan, were generated. All relationships incorporated into the biological network were drawn from public resources (including KEGG, REACTOME, INTACT, BIOGRID, and MINT). An artificial neural network analysis revealed that Sacubitril/Valsartan acts synergistically against cardiomyocyte cell death and left ventricular extracellular matrix remodeling via eight principal synergistic nodes. When studying each pathway independently, Valsartan was found to improve cardiac remodeling by inhibiting members of the guanine nucleotide-binding protein family, while Sacubitril attenuated cardiomyocyte cell death, hypertrophy, and impaired myocyte contractility by inhibiting PTEN. The complex molecular mechanisms of action of Sacubitril/Valsartan upon post-myocardial infarction and heart failure cardiac remodeling were delineated using a systems biology approach. Further, this dataset provides pathophysiological rationale for the use of Sacubitril/Valsartan to prevent post

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

    Science.gov (United States)

    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

  7. Equibiaxial cyclic stretch stimulates fibroblasts to rapidly remodel fibrin.

    Science.gov (United States)

    Balestrini, Jenna Leigh; Billiar, Kristen Lawrence

    2006-01-01

    Understanding the effects of the mechanical environment on wound healing is critical for developing more effective treatments to reduce scar formation and contracture. The aim of this study was to investigate the effects of dynamic mechanical stretch on cell-mediated early wound remodeling independent of matrix alignment which obscures more subtle remodeling mechanisms. Cyclic equibiaxial stretch (16% stretch at 0.2 Hz) was applied to fibroblast-populated fibrin gel in vitro wound models for eight days. Compaction, density, tensile strength, and collagen content were quantified as functional measures of remodeling. Stretched samples were approximately ten times stronger, eight-fold more dense, and eight times thinner than statically cultured samples. These changes were accompanied by a 15% increase in net collagen but no significant differences in cell number or viability. When collagen crosslinking was inhibited in stretched samples, the extensibility increased and the strength decreased. The apparent weakening was due to a reduction in compaction rather than a decrease in ability of the tissue to withstand tensile forces. Interestingly, inhibiting collagen crosslinking had no measurable effects on the statically cultured samples. These results indicate that amplified cell-mediated compaction and even a slight addition in collagen content play substantial roles in mechanically induced wound strengthening. These findings increase our understanding of how mechanical forces guide the healing response in skin, and the methods employed in this study may also prove valuable tools for investigating stretch-induced remodeling of other planar connective tissues and for creating mechanically robust engineered tissues.

  8. 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

  9. 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

  10. 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

  11. Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c.

    Science.gov (United States)

    Liu, Gang; Cooley, Marion A; Nair, Prema M; Donovan, Chantal; Hsu, Alan C; Jarnicki, Andrew G; Haw, Tatt Jhong; Hansbro, Nicole G; Ge, Qi; Brown, Alexandra C; Tay, Hock; Foster, Paul S; Wark, Peter A; Horvat, Jay C; Bourke, Jane E; Grainge, Chris L; Argraves, W Scott; Oliver, Brian G; Knight, Darryl A; Burgess, Janette K; Hansbro, Philip M

    2017-12-01

    Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibulin-1 (Fbln1) is an important ECM protein that stabilizes collagen and other ECM proteins. The level of Fbln1c, one of the four Fbln1 variants, which predominates in both humans and mice, is increased in the serum and airways fluids in asthma but its function is unclear. We show that the level of Fbln1c was increased in the lungs of mice with house dust mite (HDM)-induced chronic allergic airway disease (AAD). Genetic deletion of Fbln1c and therapeutic inhibition of Fbln1c in mice with chronic AAD reduced airway collagen deposition, and protected against AHR. Fbln1c-deficient (Fbln1c -/- ) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild-type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c -/- mice with AAD also had reduced numbers of α-smooth muscle actin-positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)-5, IL-13, IL-33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL-5, IL-33 and TNF levels in lung-draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3-positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL-5 and IL-13 from co-cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium-treated controls. Our data show

  12. 25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, Tomohiro [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Sugiura, Hisatoshi, E-mail: sugiura@rm.med.tohoku.ac.jp [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan); Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Ichinose, Masakazu [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan)

    2013-05-01

    Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P<0.001) and collagen I (P<0.001) expression in HFL-1. 25-HC also significantly enhanced the release and activation of matrix metallaoproteinase (MMP)-2 (P<0.001) and MMP-9 (P<0.001) without any significant effect on the production of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. 25-HC stimulated transforming growth factor (TGF)-β{sub 1} production (P<0.01) and a neutralizing anti-TGF-β antibody restored these 25-HC-augmented pro-fibrotic responses. 25-HC significantly promoted the translocation of nuclear factor (NF)-κB p65 into the nuclei (P<0.01), but not phospholylated-c-jun, a complex of activator protein-1. Pharmacological inhibition of NF-κB restored the 25-HC-augmented pro-fibrotic responses and TGF-β{sub 1} release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway.

  13. Tissue alignment enhances remodeling potential of tendon-derived cells - Lessons from a novel microtissue model of tendon scarring.

    Science.gov (United States)

    Foolen, Jasper; Wunderli, Stefania L; Loerakker, Sandra; Snedeker, Jess G

    2018-01-01

    Tendinopathy is a widespread and unresolved clinical challenge, in which associated pain and hampered mobility present a major cause for work-related disability. Tendinopathy associates with a change from a healthy tissue with aligned extracellular matrix (ECM) and highly polarized cells that are connected head-to-tail, towards a diseased tissue with a disorganized ECM and randomly distributed cells, scar-like features that are commonly attributed to poor innate regenerative capacity of the tissue. A fundamental clinical dilemma with this scarring process is whether treatment strategies should focus on healing the affected (disorganized) tissue or strengthen the remaining healthy (anisotropic) tissue. The question was thus asked whether the intrinsic remodeling capacity of tendon-derived cells depends on the organization of the 3D extracellular matrix (isotropic vs anisotropic). Progress in this field is hampered by the lack of suitable in vitro tissue platforms. We aimed at filling this critical gap by creating and exploiting a next generation tissue platform that mimics aspects of the tendon scarring process; cellular response to a gradient in tissue organization from isotropic (scarred/non-aligned) to highly anisotropic (unscarred/aligned) was studied, as was a transient change from isotropic towards highly anisotropic. Strikingly, cells residing in an 'unscarred' anisotropic tissue indicated superior remodeling capacity (increased gene expression levels of collagen, matrix metalloproteinases MMPs, tissue inhibitors of MMPs), when compared to their 'scarred' isotropic counterparts. A numerical model then supported the hypothesis that cellular remodeling capacity may correlate to cellular alignment strength. This in turn may have improved cellular communication, and could thus relate to the more pronounced connexin43 gap junctions observed in anisotropic tissues. In conclusion, increased tissue anisotropy was observed to enhance the cellular potential for

  14. Quantification of three-dimensional cell-mediated collagen remodeling using graph theory.

    Science.gov (United States)

    Bilgin, Cemal Cagatay; Lund, Amanda W; Can, Ali; Plopper, George E; Yener, Bülent

    2010-09-30

    Cell cooperation is a critical event during tissue development. We present the first precise metrics to quantify the interaction between mesenchymal stem cells (MSCs) and extra cellular matrix (ECM). In particular, we describe cooperative collagen alignment process with respect to the spatio-temporal organization and function of mesenchymal stem cells in three dimensions. We defined two precise metrics: Collagen Alignment Index and Cell Dissatisfaction Level, for quantitatively tracking type I collagen and fibrillogenesis remodeling by mesenchymal stem cells over time. Computation of these metrics was based on graph theory and vector calculus. The cells and their three dimensional type I collagen microenvironment were modeled by three dimensional cell-graphs and collagen fiber organization was calculated from gradient vectors. With the enhancement of mesenchymal stem cell differentiation, acceleration through different phases was quantitatively demonstrated. The phases were clustered in a statistically significant manner based on collagen organization, with late phases of remodeling by untreated cells clustering strongly with early phases of remodeling by differentiating cells. The experiments were repeated three times to conclude that the metrics could successfully identify critical phases of collagen remodeling that were dependent upon cooperativity within the cell population. Definition of early metrics that are able to predict long-term functionality by linking engineered tissue structure to function is an important step toward optimizing biomaterials for the purposes of regenerative medicine.

  15. Quantification of three-dimensional cell-mediated collagen remodeling using graph theory.

    Directory of Open Access Journals (Sweden)

    Cemal Cagatay Bilgin

    2010-09-01

    Full Text Available Cell cooperation is a critical event during tissue development. We present the first precise metrics to quantify the interaction between mesenchymal stem cells (MSCs and extra cellular matrix (ECM. In particular, we describe cooperative collagen alignment process with respect to the spatio-temporal organization and function of mesenchymal stem cells in three dimensions.We defined two precise metrics: Collagen Alignment Index and Cell Dissatisfaction Level, for quantitatively tracking type I collagen and fibrillogenesis remodeling by mesenchymal stem cells over time. Computation of these metrics was based on graph theory and vector calculus. The cells and their three dimensional type I collagen microenvironment were modeled by three dimensional cell-graphs and collagen fiber organization was calculated from gradient vectors. With the enhancement of mesenchymal stem cell differentiation, acceleration through different phases was quantitatively demonstrated. The phases were clustered in a statistically significant manner based on collagen organization, with late phases of remodeling by untreated cells clustering strongly with early phases of remodeling by differentiating cells. The experiments were repeated three times to conclude that the metrics could successfully identify critical phases of collagen remodeling that were dependent upon cooperativity within the cell population.Definition of early metrics that are able to predict long-term functionality by linking engineered tissue structure to function is an important step toward optimizing biomaterials for the purposes of regenerative medicine.

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    Lifescience Database Archive (English)

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  20. 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

  1. Binding of matrix metalloproteinase inhibitors to extracellular matrix: 3D-QSAR analysis.

    Science.gov (United States)

    Zhang, Yufen; Lukacova, Viera; Bartus, Vladimir; Nie, Xiaoping; Sun, Guorong; Manivannan, Ethirajan; Ghorpade, Sandeep R; Jin, Xiaomin; Manyem, Shankar; Sibi, Mukund P; Cook, Gregory R; Balaz, Stefan

    2008-10-01

    Binding to the extracellular matrix, one of the most abundant human protein complexes, significantly affects drug disposition. Specifically, the interactions with extracellular matrix determine the free concentrations of small molecules acting in tissues, including signaling peptides, inhibitors of tissue remodeling enzymes such as matrix metalloproteinases, and other drug candidates. The nature of extracellular matrix binding was elucidated for 63 matrix metalloproteinase inhibitors, for which the association constants to an extracellular matrix mimic were reported here. The data did not correlate with lipophilicity as a common determinant of structure-nonspecific, orientation-averaged binding. A hypothetical structure of the binding site of the solidified extracellular matrix surrogate was analyzed using the Comparative Molecular Field Analysis, which needed to be applied in our multi-mode variant. This fact indicates that the compounds bind to extracellular matrix in multiple modes, which cannot be considered as completely orientation-averaged and exhibit structural dependence. The novel comparative molecular field analysis models, exhibiting satisfactory descriptive and predictive abilities, are suitable for prediction of the extracellular matrix binding for the untested chemicals, which are within applicability domains. The results contribute to a better prediction of the pharmacokinetic parameters such as the distribution volume and the tissue-blood partition coefficients, in addition to a more imminent benefit for the development of more effective matrix metalloproteinase inhibitors.

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  6. 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....

  7. Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Martinez, Gerd; Midjord, Anne-Kirsten

    2016-01-01

    OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been...... of COPD, blood oxygen saturation, shuttle walk test distance, GOLD grades, or CAT scores. CONCLUSIONS: Serological biomarkers of collagen remodeling were elevated in subjects with COPD as compared with healthy individuals. Biomarker levels were significantly correlated with measures of dyspnea, indicating...... a relationship with degree of symptoms, while only C6M showed a weak but significant association with lung function. Biomarker levels were not related to GOLD grades, which was in line with previous studies indicating that ECM remodeling may be related to disease activity rather than severity....

  8. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  9. Cardiac-Restricted IGF-1Ea Overexpression Reduces the Early Accumulation of Inflammatory Myeloid Cells and Mediates Expression of Extracellular Matrix Remodelling Genes after Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Enrique Gallego-Colon

    2015-01-01

    Full Text Available Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9, their inhibitors (TIMP-1 and TIMP-2, and collagen types (Col 1α1 and Col 1α3 in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.

  10. 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...

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

    Directory of Open Access Journals (Sweden)

    Noriyuki Takai

    2010-01-01

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

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    Lifescience Database Archive (English)

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  1. Constructive remodeling of biologic scaffolds is dependent on early exposure to physiologic bladder filling in a canine partial cystectomy model.

    Science.gov (United States)

    Boruch, Alan V; Nieponice, Alejandro; Qureshi, Irfan R; Gilbert, Thomas W; Badylak, Stephen F

    2010-06-15

    Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the constructive remodeling of several tissue types. Previous studies suggest that the ECM scaffold remodeling process is dependent on microenvironmental factors, including tissue-specific biomechanical loading. The objective of the present study was to evaluate the effects of long-term catheterization (LTC), with its associated inhibition of bladder filling and physiologic biomechanical loading, on ECM scaffold remodeling following partial cystectomy in a canine model. Reconstruction of the partial cystectomy site was performed using ECM scaffolds prepared from porcine small intestinal submucosa (SIS) or porcine urinary bladder matrix (UBM). Animals were randomly assigned to either a long-term catheterization (LTC) group (n=5, catheterized 28 d) or a short-term catheterization group (STC, n=5, catheterized 24 h), and scaffold remodeling was assessed by histologic methods at 4 and 12 wk postoperatively. By 4 wk, animals in the STC group showed a well-developed and highly differentiated urothelium, a robust vascularization network, abundant smooth muscle actin (SMA), and smooth muscle myosin heavy chain (smMHC) expressing spindle-shaped cells, and many neuronal processes associated with newly formed arterioles. In contrast, at 4 wk the scaffolds in LTC animals were not epithelialized, and did not express neuronal markers. The scaffolds in the LTC group developed a dense granulation tissue containing SMA+, smMHC-, spindle-shaped cells that were morphologically and phenotypically consistent with myofibroblasts, but not smooth muscle cells. By 12 wk postoperatively, the ECM scaffolds in the STC animals showed a constructive remodeling response, with a differentiated urothelium and islands of smooth muscle cells within the remodeled scaffold. In contrast, at 12 wk the scaffolds in LTC animals had a remodeling response more consistent with fibrosis even though catheters had been

  2. 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 ...

  3. High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD – results from the ECLIPSE study

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Leeming, Diana J; Byrjalsen, Inger

    2016-01-01

    with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling. METHODS: Biomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort. Validated......BACKGROUND: There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated...... immunoassays measuring serological neo-epitopes produced by proteolytic cleavage associated with degradation of collagen type I, III, IV, and VI, elastin, and biglycan, and formation of collagen type VI as well as fibrinogen and C-reactive protein were used. Multivariate models were used to assess...

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

    Science.gov (United States)

    Heger, A; Sator, M; Pietrowski, D

    2012-08-01

    Endometrial receptivity plays a crucial role in the establishment of a healthy pregnancy in cycles of assisted reproduction. The endometrium as a key factor during reproduction can be assessed in multiple ways, most commonly through transvaginal grey-scale or 3-D ultrasound. It has been shown that controlled ovarian hyperstimulation has a great impact on the uterine lining, which leads to different study results for the predictive value of endometrial factors measured on different cycle days. There is no clear consensus on whether endometrial factors are appropriate to predict treatment outcome and if so, which one is suited best. The aim of this review is to summarize recent findings of studies about the influence of endometrial thickness, volume and pattern on IVF- and ICSI-treatment outcome and provide an overview of future developments in the field.

  5. 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.

  6. Increased Interleukin-32 Levels in Obesity Promote Adipose Tissue Inflammation and Extracellular Matrix Remodeling: Effect of Weight Loss.

    Science.gov (United States)

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Valentí, Víctor; Moncada, Rafael; Landecho, Manuel F; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

    2016-12-01

    Interleukin (IL)-32 is a recently described cytokine involved in the regulation of inflammation. We aimed to explore whether IL-32 could function as an inflammatory and angiogenic factor in human obesity and obesity-associated type 2 diabetes. Samples obtained from 90 subjects were used in the study. Obese patients exhibited higher expression levels of IL-32 in visceral adipose tissue (AT) as well as in subcutaneous AT and peripheral blood mononuclear cells. IL32 was mainly expressed by stromovascular fraction cells, and its expression was significantly enhanced by inflammatory stimuli and hypoxia, whereas no changes were found after the incubation with anti-inflammatory cytokines. The addition of exogenous IL-32 induced the expression of inflammation and extracellular matrix-related genes in human adipocyte cultures, and IL32-silenced adipocytes showed a downregulation of inflammatory genes. Furthermore, adipocyte-conditioned media obtained from obese patients increased IL32 gene expression in human monocyte cultures, whereas the adipocyte-conditioned media from lean volunteers had no effect on IL32 mRNA levels. These findings provide evidence, for the first time, about the inflammatory and remodeling properties of IL-32 in AT, implicating this cytokine in obesity-associated comorbidities. © 2016 by the American Diabetes Association.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  10. Extracellular Matrix in Plants and Animals: Hooks and Locks for Viruses

    Directory of Open Access Journals (Sweden)

    Livia Stavolone

    2017-09-01

    Full Text Available The extracellular matrix (ECM of animal and plants cells plays important roles in viral diseases. While in animal cells extracellular matrix components can be exploited by viruses for recognition, attachment and entry, the plant cell wall acts as a physical barrier to viral entry and adds a higher level of difficulty to intercellular movement of viruses. Interestingly, both in plant and animal systems, ECM can be strongly remodeled during virus infection, and the understanding of remodeling mechanisms and molecular players offers new perspectives for therapeutic intervention. This review focuses on the different roles played by the ECM in plant and animal hosts during virus infection with special emphasis on the similarities and differences. Possible biotechnological applications aimed at improving viral resistance are discussed.

  11. Avaliação de morfologia e histologia endometrial de mulheres após a menopausa Assessment of endometrial morphology and histology in postmenopausal women

    Directory of Open Access Journals (Sweden)

    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.

  12. 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 ...

  13. The Integrin-blocking Peptide RGDS Inhibits Airway Smooth Muscle Remodeling in a Guinea Pig Model of Allergic Asthma

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Bos, I. Sophie T.; Gosens, Reinoud; Halayko, Andrew J.; Zaagsma, Johan; Meurs, Herman

    2010-01-01

    Rationale: Airway remodeling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyper-responsiveness in asthma. The mechanisms driving these changes are, however, incompletely understood. Recently, an important role for extracellular matrix proteins in

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Jehn-Hsiahn Yang

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

  16. Extracellular matrix structure.

    Science.gov (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

    2016-02-01

    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Lifescience Database Archive (English)

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

    Directory of Open Access Journals (Sweden)

    Allison Jones

    2013-11-01

    Full Text Available Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development.Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64 and control samples (n = 23 revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A. Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop

  2. Periostin is an extracellular matrix protein required for eruption of incisors in mice

    International Nuclear Information System (INIS)

    Kii, Isao; Amizuka, Norio; Minqi, Li; Kitajima, Satoshi; Saga, Yumiko; Kudo, Akira

    2006-01-01

    A characteristic tooth of rodents, the incisor continuously grows throughout life by the constant formation of dentin and enamel. Continuous eruption of the incisor is accompanied with formation of shear zone, in which the periodontal ligament is remodeled. Although the shear zone plays a role in the remodeling, its molecular biological aspect is barely understood. Here, we show that periostin is essential for formation of the shear zone. Periostin -/- mice showed an eruption disturbance of incisors. Histological observation revealed that deletion of periostin led to disappearance of the shear zone. Electron microscopy revealed that the disappearance of the shear zone resulted from a failure in digestion of collagen fibers in the periostin -/- mice. Furthermore, immunohistochemical analysis using anti-periostin antibodies demonstrated the restricted localization of periostin protein in the shear zone. Periostin is an extracellular matrix protein, and immunoelectron microscopy showed a close association of periostin with collagen fibrils in vivo. These results suggest that periostin functions in the remodeling of collagen matrix in the shear zone

  3. The role of miRNAs in endometrial cancer.

    Science.gov (United States)

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

    2015-01-01

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

  4. Prevalence of Human Papillomavirus in endometrial cancer

    DEFF Research Database (Denmark)

    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....

  5. 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

  6. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

  7. Assessment of Myocardial Remodeling Using an Elastin/Tropoelastin Specific Agent with High Field Magnetic Resonance Imaging (MRI).

    Science.gov (United States)

    Protti, Andrea; Lavin, Begoña; Dong, Xuebin; Lorrio, Silvia; Robinson, Simon; Onthank, David; Shah, Ajay M; Botnar, Rene M

    2015-08-13

    Well-defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction (MI) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin-specific contrast agent (Gd-ESMA) was used to image tropoelastin and mature elastin fibers for in vivo assessment of extracellular matrix remodeling post-MI. Gd-ESMA enhancement was studied in a mouse model of myocardial infarction using a 7 T MRI scanner and results were compared to those achieved after injection of a nonspecific control contrast agent, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In the infarcted tissue, Gd-ESMA uptake (measured as R1 relaxation rate) steadily increased from day 3 to day 21 as a result of the synthesis of elastin/tropoelastin. R1 values were in good agreement with histological findings. A similar R1 behavior was observed in the remote myocardium. No mature cross-linked elastin was found at any time point. In contrast, Gd-DTPA uptake was only observed in the infarct with no changes in R1 values between 3 and 21 days post-MI. We demonstrate the feasibility of in vivo imaging of extracellular matrix remodeling post-MI using a tropoelastin/elastin binding MR contrast agent, Gd-ESMA. We found that tropoelastin is the main contributor to the increased MRI signal at late stages of MI where its augmentation in areas of infarction was in good agreement with the R1 increase. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

    Science.gov (United States)

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

    2013-01-01

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

  9. 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.

  10. 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

  11. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    Directory of Open Access Journals (Sweden)

    Dermot Phelan

    Full Text Available In asymptomatic subjects B-type natriuretic peptide (BNP is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS and peripheral serum from patients with low (n = 14 and high BNP (n = 27. Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001. CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008, CITP (r = 0.35, p = 0.03 and PIIINP (r = 0.35, p = 0.001, and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002, IL-6 (r = 0.35, p = 0.04, and IL-8 (r = 0.54, p<0.001. The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007, TNF-α (3.2±0.5 versus 3.7±1.1, p = 003, IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02 and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04, and greater left ventricular mass index (97±20 versus 118±26 g/m(2, p = 0.03 and left atrial volume index (18±2 versus 21±4, p = 0.008. Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  12. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    LENUS (Irish Health Repository)

    Phelan, Dermot

    2012-11-01

    In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g\\/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  13. 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

  14. 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.

  15. Effects of particle size and porosity on in vivo remodeling of settable allograft bone/polymer composites.

    Science.gov (United States)

    Prieto, Edna M; Talley, Anne D; Gould, Nicholas R; Zienkiewicz, Katarzyna J; Drapeau, Susan J; Kalpakci, Kerem N; Guelcher, Scott A

    2015-11-01

    Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity and high viscosity grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105-500 μm) allograft particles healed at 12 weeks postimplantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. © 2015 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

    Full Text Available Oth.Utr.05.AllAg.Endometrial_stromal_cells hg19 TFs and others Uterus Endometrial s...tromal cells SRX1048945,SRX1048948,SRX1048946,SRX372174,SRX735140,SRX735139 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Utr.05.AllAg.Endometrial_stromal_cells.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Oth.Utr.10.AllAg.Endometrial_stromal_cells hg19 TFs and others Uterus Endometrial s...tromal cells SRX1048945,SRX1048948,SRX1048946,SRX372174,SRX735140,SRX735139 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Utr.10.AllAg.Endometrial_stromal_cells.bed ...

  2. 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.

  3. 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.)

  4. 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...

  5. Diagnosis of endometrial tuberculosis: culture versus histopathological examination

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  6. 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.

  7. 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

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    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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  11. 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 ...

  12. 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.

  13. Impact of Persistent Intracellular Infections on the Processes of Airway Remodeling in Children with Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    O.Ye. Chernyshova

    2015-03-01

    Full Text Available The article presents information about the impact of persistent intracellular infections on the processes of airway remodeling in bronchial asthma in children. The influence of matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase, transforming growth factor, antibodies to type III collagen, endothelin-1 on the processes of morphological reconstruction of the airway by way of smooth muscle hypertrophy, enhanced neovascularization, epithelial cell hyperplasia, collagen deposition, thickening of the basal membrane, observed in bronchial asthma in children, were described.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

    Science.gov (United States)

    Chen, Juanjuan; Khalil, Raouf A.

    2017-01-01

    Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. Increases in MMP-2 and MMP-9 have been implicated in vasodilation, placentation and uterine expansion during normal pregnancy. The increases in MMPs could be induced by the increased production of estrogen and progesterone during pregnancy. MMP expression/activity may be altered during complications of pregnancy. Decreased vascular MMP-2 and MMP-9 may lead to decreased vasodilation, increased vasoconstriction, hypertensive pregnancy and preeclampsia. Abnormal expression of uteroplacental integrins, cytokines and MMPs may lead to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate remodeling of spiral arteries, and reduced uterine perfusion pressure (RUPP). RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, or stimulate the release of inflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could target MMPs in the extracellular matrix as well as endothelial and vascular smooth muscle cells, causing generalized vascular dysfunction, increased vasoconstriction and hypertension in pregnancy. MMP activity can also be altered by endogenous tissue inhibitors of metalloproteinases (TIMPs) and changes in the MMP/TIMP ratio. In addition to their vascular effects, decreases in expression/activity of MMP-2 and MMP-9 in the uterus could impede uterine growth and expansion and lead to premature labor. Understanding the role of MMPs in uteroplacental and

  19. 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.

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

    Science.gov (United States)

    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

  1. Inelastic behaviour of collagen networks in cell–matrix interactions and mechanosensation

    Science.gov (United States)

    Mohammadi, Hamid; Arora, Pamma D.; Simmons, Craig A.; Janmey, Paul A.; McCulloch, Christopher A.

    2015-01-01

    The mechanical properties of extracellular matrix proteins strongly influence cell-induced tension in the matrix, which in turn influences cell function. Despite progress on the impact of elastic behaviour of matrix proteins on cell–matrix interactions, little is known about the influence of inelastic behaviour, especially at the large and slow deformations that characterize cell-induced matrix remodelling. We found that collagen matrices exhibit deformation rate-dependent behaviour, which leads to a transition from pronounced elastic behaviour at fast deformations to substantially inelastic behaviour at slow deformations (1 μm min−1, similar to cell-mediated deformation). With slow deformations, the inelastic behaviour of floating gels was sensitive to collagen concentration, whereas attached gels exhibited similar inelastic behaviour independent of collagen concentration. The presence of an underlying rigid support had a similar effect on cell–matrix interactions: cell-induced deformation and remodelling were similar on 1 or 3 mg ml−1 attached collagen gels while deformations were two- to fourfold smaller in floating gels of high compared with low collagen concentration. In cross-linked collagen matrices, which did not exhibit inelastic behaviour, cells did not respond to the presence of the underlying rigid foundation. These data indicate that at the slow rates of collagen compaction generated by fibroblasts, the inelastic responses of collagen gels, which are influenced by collagen concentration and the presence of an underlying rigid foundation, are important determinants of cell–matrix interactions and mechanosensation. PMID:25392399

  2. 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...

  3. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves.

    Directory of Open Access Journals (Sweden)

    Philip R Buskohl

    Full Text Available Embryonic heart valve primordia (cushions maintain unidirectional blood flow during development despite an increasingly demanding mechanical environment. Recent studies demonstrate that atrioventricular (AV cushions stiffen over gestation, but the molecular mechanisms of this process are unknown. Transforming growth factor-beta (TGFβ and serotonin (5-HT signaling modulate tissue biomechanics of postnatal valves, but less is known of their role in the biomechanical remodeling of embryonic valves. In this study, we demonstrate that exogenous TGFβ3 increases AV cushion biomechanical stiffness and residual stress, but paradoxically reduces matrix compaction. We then show that TGFβ3 induces contractile gene expression (RhoA, aSMA and extracellular matrix expression (col1α2 in cushion mesenchyme, while simultaneously stimulating a two-fold increase in proliferation. Local compaction increased due to an elevated contractile phenotype, but global compaction appeared reduced due to proliferation and ECM synthesis. Blockade of TGFβ type I receptors via SB431542 inhibited the TGFβ3 effects. We next showed that exogenous 5-HT does not influence cushion stiffness by itself, but synergistically increases cushion stiffness with TGFβ3 co-treatment. 5-HT increased TGFβ3 gene expression and also potentiated TGFβ3 induced gene expression in a dose-dependent manner. Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter (SERT, resulted in complete cessation of TGFβ3 induced mechanical strengthening. Finally, systemic 5-HT administration in ovo induced cushion remodeling related defects, including thinned/atretic AV valves, ventricular septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in elevated remodeling gene expression and increased TGFβ signaling activity, supporting our ex-vivo findings. Collectively, these results highlight TGFβ/5-HT signaling as a potent mechanism for control of biomechanical

  7. 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...

  8. 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).

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

    Science.gov (United States)

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

    2017-12-18

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

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

    Directory of Open Access Journals (Sweden)

    Beata Leśniczak

    2015-09-01

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

  11. FK506 protects against articular cartilage collagenous extra-cellular matrix degradation

    NARCIS (Netherlands)

    M. Siebelt (Michiel); A.E. van der Windt (Anna); H.C. Groen (Harald); M. Sandker (Marjan); J.H. Waarsing (Jan); C. Müller (Cristina); M. de Jong (Marcel); H. Jahr (Holger); H.H. Weinans (Harrie)

    2014-01-01

    textabstractObjective: Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn)

  12. Decomposition cross-correlation for analysis of collagen matrix deformation by single smooth muscle cells

    NARCIS (Netherlands)

    van den Akker, Jeroen; Pistea, Adrian; Bakker, Erik N. T. P.; VanBavel, Ed

    2008-01-01

    Microvascular remodeling is known to depend on cellular interactions with matrix tissue. However, it is difficult to study the role of specific cells or matrix elements in an in vivo setting. The aim of this study is to develop an automated technique that can be employed to obtain and analyze local

  13. 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

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

    Science.gov (United States)

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

    2015-07-01

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

  15. Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition

    NARCIS (Netherlands)

    C.J. Slager (Cornelis); J. Kloet (Jeroen); J.A.F. Oomen; J.C.H. Schuurbiers (Johan); B.J. de Smet; M.J. Post (Mark); D.P.V. de Kleijn (Dominique); G. Pasterkamp (Gerard); R. Krams (Rob); C. Borst (Cornelius); J.J. Wentzel (Jolanda); I. Andhyiswara (Ivan)

    2001-01-01

    textabstractBACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA

  16. 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.

  17. The provisional matrix: setting the stage for tissue repair outcomes.

    Science.gov (United States)

    Barker, Thomas H; Engler, Adam J

    2017-07-01

    Since its conceptualization in the 1980s, the provisional matrix has often been characterized as a simple fibrin-containing scaffold for wound healing that supports the nascent blood clot and is functionally distinct from the basement membrane. However subsequent advances have shown that this matrix is far from passive, with distinct compositional differences as the wound matures, and providing an active role for wound remodeling. Here we review the stages of this matrix, provide an update on the state of our understanding of provisional matrix, and present some of the outstanding issues related to the provisional matrix, its components, and their assembly and use in vivo. Copyright © 2017. Published by Elsevier B.V.

  18. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  19. 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...

  20. Assessment of reliability of endometrial brush cytology to determine the etiology of abnormal uterine bleeding and postmenopausal bleeding

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    Delphine Haouzi

    2014-01-01

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

  2. Effects of dynamic matrix remodelling on en masse migration of fibroblasts on collagen matrices.

    Science.gov (United States)

    Ozcelikkale, Altug; Dutton, J Craig; Grinnell, Frederick; Han, Bumsoo

    2017-10-01

    Fibroblast migration plays a key role during various physiological and pathological processes. Although migration of individual fibroblasts has been well studied, migration in vivo often involves simultaneous locomotion of fibroblasts sited in close proximity, so-called ' en masse migration', during which intensive cell-cell interactions occur. This study aims to understand the effects of matrix mechanical environments on the cell-matrix and cell-cell interactions during en masse migration of fibroblasts on collagen matrices. Specifically, we hypothesized that a group of migrating cells can significantly deform the matrix, whose mechanical microenvironment dramatically changes compared with the undeformed state, and the alteration of the matrix microenvironment reciprocally affects cell migration. This hypothesis was tested by time-resolved measurements of cell and extracellular matrix movement during en masse migration on collagen hydrogels with varying concentrations. The results illustrated that a group of cells generates significant spatio-temporal deformation of the matrix before and during the migration. Cells on soft collagen hydrogels migrate along tortuous paths, but, as the matrix stiffness increases, cell migration patterns become aligned with each other and show coordinated migration paths. As cells migrate, the matrix is locally compressed, resulting in a locally stiffened and dense matrix across the collagen concentration range studied. © 2017 The Author(s).

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

    Science.gov (United States)

    Holden, Emily C; Dodge, Laura E; Sneeringer, Rita; Moragianni, Vasiliki A; Penzias, Alan S; Hacker, Michele R

    2017-06-18

    Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09-1.18) and live birth (RR: 1.08; 95% CI: 1.05-1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91-1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11 mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11 mm (adjusted RR: 1.23; 95% CI: 1.11-1.37) and significantly lower for the ≤7 mm group (adjusted RR: 0.64; 95% CI: 0.45-0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  5. 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

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

    Directory of Open Access Journals (Sweden)

    Nicolae Bacalbasa

    2018-05-01

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

  7. 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

  8. Callus remodelling model

    Science.gov (United States)

    Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

    2018-01-01

    The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

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

    Directory of Open Access Journals (Sweden)

    Wiesława Niklińska

    2009-05-01

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

  10. 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

  11. 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)

  12. 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

  13. In vivo extracellular matrix protein expression by human periodontal ...

    African Journals Online (AJOL)

    It is well known that the orthodontic force applied to teeth generates a series of events that remodel the periodontal ligament (PDL). Extracellular matrix proteins (ECM) are described as molecular regulators of these events. However, the exact contribution of these proteins in human PDL modeling by orthodontic force ...

  14. Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors.

    NARCIS (Netherlands)

    Snoek, P.A.; Hoff, J.W. Von den

    2005-01-01

    The balance between matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), is largely responsible for the remodeling of tissues. Deregulation of this balance is a characteristic of extensive tissue degradation in certain degenerative diseases. To

  15. Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the invasiveness of endometrial cancer cells through the GnRH-I receptor and mitogen-activated protein kinase (MAPK)-dependent activation of matrix metalloproteinase (MMP)-2

    International Nuclear Information System (INIS)

    Wu, Hsien-Ming; Wang, Hsin-Shih; Huang, Hong-Yuan; Lai, Chyong-Huey; Lee, Chyi-Long; Soong, Yung-Kuei; Leung, Peter CK

    2013-01-01

    More than 25% of patients diagnosed with endometrial carcinoma have an invasive primary cancer accompanied by metastases. Gonadotropin-releasing hormone (GnRH) plays an important role in reproduction. In mammals, expression of GnRH-II is higher than GnRH-I in reproductive tissues. Here, we examined the effect of a GnRH-II agonist on the motility of endometrial cancer cells and its mechanism of action in endometrial cancer therapy. Immunoblotting and immunohistochemistry (IHC) were used to determine the expression of the GnRH-I receptor protein in human endometrial cancer. The activity of MMP-2 in the conditioned medium was determined by gelatin zymography. Cell motility was assessed by invasion and migration assay. GnRH-I receptor si-RNA was applied to knockdown GnRH-I receptor. The GnRH-I receptor was expressed in the endometrial cancer cells. The GnRH-II agonist promoted cell motility in a dose-dependent manner. The GnRH-II agonist induced the phosphorylation of ERK1/2 and JNK, and the phosphorylation was abolished by ERK1/2 inhibitor (U0126) and the JNK inhibitor (SP600125). Cell motility promoted by GnRH-II agonist was suppressed in cells that were pretreated with U0126 and SP600125. Moreover, U0126 and SP600125 abolished the GnRH-II agonist-induced activation of MMP-2. The inhibition of MMP-2 with MMP-2 inhibitor (OA-Hy) suppressed the increase in cell motility in response to the GnRH-II agonist. Enhanced cell motility mediated by GnRH-II agonist was also suppressed by the knockdown of the endogenous GnRH-I receptor using siRNA. Our study indicates that GnRH-II agonist promoted cell motility of endometrial cancer cells through the GnRH-I receptor via the phosphorylation of ERK1/2 and JNK, and the subsequent, MAPK-dependent activation of MMP-2. Our findings represent a new concept regarding the mechanism of GnRH-II-induced cell motility in endometrial cancer cells and suggest the possibility of exploring GnRH-II as a potential therapeutic target for the

  16. 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.

  17. 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...

  18. Assessment of Matrix Metalloproteinases by Gelatin Zymography.

    Science.gov (United States)

    Cathcart, Jillian

    2016-01-01

    Matrix metalloproteinases are endopeptidases responsible for remodeling of the extracellular matrix and have been identified as critical contributors to breast cancer progression. Gelatin zymography is a valuable tool which allows the analysis of MMP expression. In this approach, enzymes are resolved electrophoretically on a sodium dodecyl sulfate-polyacrylamide gel copolymerized with the substrate for the MMP of interest. Post electrophoresis, the enzymes are refolded in order for proteolysis of the incorporated substrate to occur. This assay yields valuable information about MMP isoforms or changes in activation and can be used to analyze the role of MMPs in normal versus pathological conditions.

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

    Directory of Open Access Journals (Sweden)

    Leslie Kimberly K

    2011-08-01

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

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

    Science.gov (United States)

    Ip, Philip Pun-Ching

    2018-02-14

    Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial 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.

  1. Inflammatory responses, matrix remodeling, and re-epithelialization after fractional CO2 laser treatment of scars.

    Science.gov (United States)

    DeBruler, Danielle M; Blackstone, Britani N; Baumann, Molly E; McFarland, Kevin L; Wulff, Brian C; Wilgus, Traci A; Bailey, J Kevin; Supp, Dorothy M; Powell, Heather M

    2017-09-01

    Fractional CO 2 laser therapy has been used to improve scar pliability and appearance; however, a variety of treatment protocols have been utilized with varied outcomes. Understanding the relationship between laser power and extent of initial tissue ablation and time frame for remodeling could help determine an optimum power and frequency for laser treatment. The characteristics of initial injury caused by fractional CO 2 laser treatment, the rates of dermal remodeling and re-epithelialization, and the extent of inflammation as a function of laser stacking were assessed in this study in a porcine scar model. Full-thickness burn wounds were created on female Red Duroc pigs followed by immediate excision of the eschar and split-thickness autografting. Three months after injury, the resultant scars were treated with a fractional CO 2 laser with 70 mJ of energy delivered as either a single pulse or stacked for three consecutive pulses. Immediately prior to laser treatment and at 1, 24, 96, and 168 hours post-laser treatment, transepidermal water loss (TEWL), erythema, and microscopic characteristics of laser injury were measured. In addition, markers for inflammatory cytokines, extracellular matrix proteins, and re-epithelialization were quantified at all time points using qRT-PCR. Both treatments produced erythema in the scar that peaked 24 hours after treatment then decreased to basal levels by 168 hours. TEWL increased after laser treatment and returned to normal levels between 24 and 96 hours later. Stacking of the pulses did not significantly increase the depth of ablated wells or extend the presence of erythema. Interleukin 6 and monocyte chemoattractant protein-1 were found to increase significantly 1 hour after treatment but returned to baseline by 24 hours post laser. In contrast, expression of transforming growth factor β1 and transforming growth factor β3 increased slowly after treatment with a more modest increase than interleukin 6 and monocyte

  2. 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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Okulicz William C

    2004-07-01

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

  5. Extracellular matrix hydrogels from decellularized tissues: Structure and function.

    Science.gov (United States)

    Saldin, Lindsey T; Cramer, Madeline C; Velankar, Sachin S; White, Lisa J; Badylak, Stephen F

    2017-02-01

    Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed. More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. 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

    Can the presence of endometrial nerve fibres be used as a diagnostic test for endometriosis in women with pelvic pain? Endometrial fine nerve fibres were seen in the endometrium of women both with and without endometriosis, making their detection a poor diagnostic tool for endometriosis. Laparoscopy and biopsy are currently the gold standard for making a diagnosis of endometriosis. It has been reported that small density nerve fibres in the functional layer of the endometrium are unique to women with endometriosis and hence nerve fibre detection could function as a less invasive diagnostic test of endometriosis. However, it may be that other painful conditions of the pelvis are also associated with these nerve fibres. We therefore focused this prospective study on women with pelvic pain to examine the efficacy of endometrial nerve fibre detection as a diagnostic test for endometriosis. This prospective case-control study conducted between July 2009 and July 2013 included 44 women with pelvic pain undergoing laparoscopic examination for the diagnosis of endometriosis. Immunohistochemical nerve fibre detection in endometrial curettings and biopsies using anti-protein gene product 9.5 was compared with surgical diagnosis. Paired endometrial biopsies and curettings were taken from patients with (n = 22, study group) and without (n = 22, control group) endometriosis. Tissue was analysed by immunohistochemistry and nerve fibres were counted whenever they were present in the functional layer of the endometrium. Fine nerve fibres were present in the eutopic endometrium of patients both with and without endometriosis. The presence of nerve fibres in curettings was not effective for either diagnosing or excluding endometriosis; sensitivity and specificity were 31.8 and 45.5% respectively, positive predictive value was 36.8% and negative predictive value was 40.0%. Few endometrial biopsy specimens were found to have nerve fibres present; sensitivity and specificity for

  7. Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity.

    Science.gov (United States)

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Salvador, Javier; Frühbeck, Gema

    2012-10-01

    Obesity is associated with an altered inflammatory and extracellular matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with proinflammatory effects. We aimed to explore the expression levels of TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular fraction cells (SVFC) as well as its impact on inflammation and ECM regulation. We also analyzed the effect of the stimulation with TNF-α and lipopolysaccharide (LPS) on both SVFC and adipocytes. Samples obtained from 75 subjects were used in the study. Expression levels of TNC, TLR4, MMP2, and MMP9 were analyzed in visceral adipose tissue (VAT) as well as in both adipocytes and SVFC. In addition, Tnc expression was measured in two mice models of obesity. We show, for the first time, that VAT expression levels of TNC are increased in normoglycemic and type 2 diabetic obese patients (Pobese patients with nonalcoholic steatohepatitis (Pobesity were significantly increased (Pexogenous TNC induced (Pobesity via visceral adipose tissue inflammation representing a link with ECM remodeling.

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis

    DEFF Research Database (Denmark)

    Vassiliadis, Efstathios; Veidal, Sanne Skovgård; Simonsen, Henrik

    2011-01-01

    AIM: Liver fibrosis involves excessive remodeling and deposition of fibrillar extracellular matrix (ECM) components, which leads to malfunction of the organ, causing significant morbidity and mortality. The aim of this study was to assess whether levels of a type V collagen fragment, the propepti...

  15. Intermittent Hypoxia-Induced Cardiovascular Remodeling Is Reversed by Normoxia in a Mouse Model of Sleep Apnea.

    Science.gov (United States)

    Castro-Grattoni, Anabel L; Alvarez-Buvé, Roger; Torres, Marta; Farré, Ramon; Montserrat, Josep M; Dalmases, Mireia; Almendros, Isaac; Barbé, Ferran; Sánchez-de-la-Torre, Manuel

    2016-06-01

    Intermittent hypoxia (IH) is the principal injurious factor involved in the cardiovascular morbidity and mortality associated with OSA. The gold standard for treatment is CPAP, which eliminates IH and appears to reduce cardiovascular risk. There is no experimental evidence on the reversibility of cardiovascular remodeling after IH withdrawal. The objective of the present study is to assess the reversibility of early cardiovascular structural remodeling induced by IH after resumption of normoxic breathing in a novel recovery animal model mimicking OSA treatment. We investigated cardiovascular remodeling in C57BL/6 mice exposed to IH for 6 weeks vs the normoxia group and its spontaneous recovery after 6 subsequent weeks under normoxia. Aortic expansive remodeling was induced by IH, with intima-media thickening and without lumen perimeter changes. Elastic fiber network disorganization, fragmentation, and estrangement between the end points of disrupted fibers were increased by IH. Extracellular matrix turnover was altered, as visualized by collagen and mucoid interlaminar accumulation. Furthermore, left ventricular perivascular fibrosis was increased by IH, whereas cardiomyocytes size was unaffected. These cardiovascular remodeling events induced by IH were normalized after recovery in normoxia, mimicking CPAP treatment. The early structural cardiovascular remodeling induced by IH was normalized after IH removal, revealing a novel recovery model for studying the effects of OSA treatment. Our findings suggest the clinical relevance of early detection and effective treatment of OSA in patients to prevent the natural course of cardiovascular diseases. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  17. 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

  18. 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

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

    Science.gov (United States)

    Jurczyk, Mieczysława U; Chmaj-Wierzchowska, Karolina; Klofik, Joanna; Sajdak, Stefan; Opala, Tomasz

    2013-01-01

    Approximately 1 in 20 female cancers in Europe is of the endometrium. Endometrial carcinoma is the most common gynaecologic cancer. Considering the fact that an upward tendency has recently been observed in morbidity due to this type of cancer, this is a serious medical problem. The presented report describes the results of the analysis of selected demographic factors and their effect on the incidence of endometrial cancer. Analysis of the results of treatment of endometrial cancer during 1995-2010 was also an objective of the study. Based on medical records obtained from the HDR Laboratory of Brachytherapy at the Gynaecological & Obstetrics Clinical Hospital, University of Medical Sciences in Poznań, the results of treatment of patients with endometrial cancer by brachytherapy were analyzed. The analysis covered a group of 400 patients. More than a half of the patients completed their education on the level of elementary or secondary school. Taking into consideration the weight of the patients, it appeared that most women had excessive body weight. Most frequently, concomitant hypertension was observed. Moreover, the age at menarche was 12 and 13. Demographic factors exert a significant effect on the incidence of endometrial cancer. 1. Overweight and obesity are important risk factors of endometrial cancer. 2. A strong relationship is observed between the occurrence of hypertension or diabetes, and the development of endometrial cancer. 3. Women who come from the rural environment and continue to live in this environment are more likely to contract endometrial cancer.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Owuor, Theresa O; Reid, Michaela; Reschke, Lauren; Hagemann, Ian; Greco, Suellen; Modi, Zeel; Moley, Kelle H

    2018-01-01

    Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain. While offspring fed a HF/HS post-weaning diet resulted in poor metabolic health and decreased uterine weight (regardless of maternal diet), it did not lead to ECa. We also investigated the effects of the maternal obesogenic diet on ECa development in a Diethylstilbestrol (DES) carcinogenesis mouse model. All mice injected with DES had reproductive tract lesions including decreased number of glands, condensed and hyalinized endometrial stroma, and fibrosis and increased collagen deposition that in some mice extended into the myometrium resulting in extensive disruption and loss of the inner and outer muscular layers. Fifty percent of DES mice that were exposed to maternal HF/HS diet developed several features indicative of the initial stages of carcinogenesis including focal glandular and atypical endometrial hyperplasia versus 0% of their Chow counterparts. There was an increase in phospho-Akt expression in DES mice exposed to maternal HF/HS diet, a regulator of persistent proliferation in the endometrium, and no difference in total Akt, phospho-PTEN and total PTEN expression. In summary, maternal HF/HS diet exposure induces endometrial hyperplasia and other precancerous phenotypes in mice treated with DES. This study suggests that maternal obesity alone is not sufficient for the development of ECa, but has an additive effect in the presence of a secondary insult such as DES.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Effect of Radiofrequency Endometrial Ablation on Dysmenorrhea.

    Science.gov (United States)

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

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

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

    Directory of Open Access Journals (Sweden)

    Edison Natal Fedrizzi

    2004-05-01

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

  5. Novel serological neo-epitope markers of extracellular matrix proteins for the detection of portal hypertension

    DEFF Research Database (Denmark)

    Leeming, Diana Julie; Karsdal, M A; Byrjalsen, I

    2013-01-01

    The hepatic venous pressure gradient (HVPG) is an invasive, but important diagnostic and prognostic marker in cirrhosis with portal hypertension (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process generating small fragments of degrade...... extracellular matrix (ECM) proteins known as neoepitopes, which are then released into the circulation....

  6. 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...

  7. 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...

  8. 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...

  9. 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.

  10. Hysteroscopic endometrial resection: efficacy and factors for failure

    Directory of Open Access Journals (Sweden)

    Geraldo Rodrigues de Lima

    2008-09-01

    Full Text Available Objective: To evaluate the effectiveness of hysteroscopic endometrial ablation in women with abnormal benign uterine bleeding resistant to clinical treatment, and to identify factors potentially related to its failure. Methods: Ninety patients with abnormal benign uterine bleeding were retrospectively evaluated. They were submitted to endometrial ablation between January 2000 and August 2003. Their mean age was 44.3 years and their average parity was 2.3 childbirths. All patients had been given gonadotrophin-releasing hormone analogues prior to surgery, to make the procedure easier. Rresults: After surgery, amenorrhea occurred in 20% of cases, hypomenorrhea in 30%, and eumenorrhea in 32.2%. In 17.8% of patients, the procedure failed. No intra or postoperative complications occurred. There was no statistically significant difference between the patients in which the ablation failed and those in which it was successful regarding mean age (p = 0.557, parity (p = 0.891, presence of intramural myoma (p= 0.29, submucosal myoma (p = 0.68 or endometrial polyps (p = 0.76. A significant difference between the two groups was observed with regard to the uterine size median (7  cm in the successful group and 9 cm in the failure group, p  = 0.008. A statistically significant difference was also found in follow-up time: 13 months in the first group and nine months in the second group (p = 0.001. Cconclusions: Endometrial ablation is a good treatment method for abnormal uterine bleeding of benign etiology. Special attention must be paid to patients with increased uterine size, since failure is more frequent in these cases.

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

    Directory of Open Access Journals (Sweden)

    Olga Grechukhina

    2018-01-01

    Full Text Available Background. Bardet-Biedl Syndrome (BBS is a rare genetic condition characterized by cognitive impairment, dysmorphism, central obesity, and diabetes mellitus, among other abnormalities. Although some of these characteristics are known independent risk factors for endometrial cancer and its precursors, the association between BBS and endometrial cancer is underreported. Case. We present the case of a 26-year-old patient with BBS and clinical signs of hyperestrogenism who presented with abnormal uterine bleeding and was diagnosed with endometrioid adenocarcinoma. She ultimately underwent definitive surgical treatment with hysterectomy and bilateral salpingectomy. Conclusions. This is one of only a few reports in the literature describing the association of BBS and endometrioid endometrial adenocarcinoma. Given the association of BBS with risk factors for hyperestrogenism such as truncal obesity, hyperinsulinemia, and ovulatory dysfunction, providers should have increased suspicion for endometrial cancer in young patients with BBS and abnormal uterine bleeding.

  12. Effects of aging and resistance training in rat tendon remodeling.

    Science.gov (United States)

    Marqueti, Rita C; Durigan, João L Q; Oliveira, Anderson José S; Mekaro, Marcelo Shinyu; Guzzoni, Vinicius; Aro, Andrea A; Pimentel, Edson Rosa; Selistre-de-Araujo, Heloisa S

    2018-01-01

    In elderly persons, weak tendons contribute to functional limitations, injuries, and disability, but resistance training can attenuate this age-related decline. We evaluated the effects of resistance training on the extracellular matrix (ECM) of the calcaneal tendon (CT) in young and old rats and its effect on tendon remodeling. Wistar rats aged 3 mo (young, n = 30) and 20 mo (old, n = 30) were divided into 4 groups: young sedentary, young trained, old sedentary (OS), and old trained (OT). The training sessions were conducted over a 12-wk period. Aging in sedentary rats showed down-regulation in key genes that regulated ECM remodeling. Moreover, the OS group showed a calcification focus in the distal region of the CT, with reduced blood vessel volume density. In contrast, resistance training was effective in up-regulating connective tissue growth factor, VEGF, and decorin gene expression in old rats. Resistance training also increased proteoglycan content in young and old rats in special small leucine-rich proteoglycans and blood vessels and prevented calcification in OT rats. These findings confirm that resistance training is a potential mechanism in the prevention of aging-related loss in ECM and that it attenuates the detrimental effects of aging in tendons, such as ruptures and tendinopathies.-Marqueti, R. C., Durigan, J. L. Q., Oliveira, A. J. S., Mekaro, M. S., Guzzoni, V., Aro, A. A., Pimentel, E. R., Selistre-de-Araujo, H. S. Effects of aging and resistance training in rat tendon remodeling. © FASEB.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  17. 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

  18. 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.

  19. Implication of MMP and TIMP in the matrice remodeling: early and delayed radiation effects of the digestive tractus

    International Nuclear Information System (INIS)

    Strup-Perrot, C.

    2004-12-01

    irradiation induces a marked acute remodeling of the gut wall and may lead to late fibrosis. Combining morphological, biochemical and molecular approach, we studied the expression of MMP and TIMP in the ileum and colon of rats one to seven days after irradiation and in ileum of patients with radiation enteritis. In both studies expression and activity of MMP and TIMP were increased, their balance being in favor of extra-cellular matrix degradation in the acute phase while in favor of matrix accumulation in radiation enteritis. (author)

  20. 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.

  1. Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker--Rationale and design of the trial.

    Science.gov (United States)

    Tomasik, Andrzej; Jacheć, Wojciech; Wojciechowska, Celina; Kawecki, Damian; Białkowska, Beata; Romuk, Ewa; Gabrysiak, Artur; Birkner, Ewa; Kalarus, Zbigniew; Nowalany-Kozielska, Ewa

    2015-05-01

    Dual chamber pacing is known to have detrimental effect on cardiac performance and heart failure occurring eventually is associated with increased mortality. Experimental studies of pacing in dogs have shown contractile dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel, studies on experimental ischemia/reperfusion injury have shown efficacy of valsartan to inhibit activity of matrix metalloproteinase-9, to increase the activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global contractility and left ventricle ejection fraction. To present rationale and design of randomized blinded trial aimed to assess whether 12 month long administration of valsartan will prevent left ventricle remodeling in patients with preserved left ventricle ejection fraction (LVEF ≥ 40%) and first implantation of dual chamber pacemaker. A total of 100 eligible patients will be randomized into three parallel arms: placebo, valsartan 80 mg/daily and valsartan 160 mg/daily added to previously used drugs. The primary endpoint will be assessment of valsartan efficacy to prevent left ventricle remodeling during 12 month follow-up. We assess patients' functional capacity, blood plasma activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP, tumor necrosis factor alpha, and Troponin T. Left ventricle function and remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler imaging. If valsartan proves effective, it will be an attractive measure to improve long term prognosis in aging population and increasing number of pacemaker recipients. ClinicalTrials.org (NCT01805804). Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Radiation-induced circumscribed superficial morphea after brachytherapy for endometrial adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Apoorva Trivedi, BS

    2017-12-01

    Full Text Available Radiation-induced morphea (RIM is a rare and underrecognized complication of radiation therapy that most commonly occurs in women after treatment for breast cancer. Although not fully understood, RIM is hypothesized to arise from an increase in cytokines that stimulate collagen production and extracellular matrix formation. Most documented cases of RIM occur 1 year after radiation therapy and are localized to areas that were treated for breast cancer. We report on a case of a female patient with stage IB endometrial adenocarcinoma who was treated with 24 Gray of adjuvant brachytherapy. The patient developed a diffuse morpheaform, pruritic eruption only at distant sites from the brachytherapy treatment field. Although treatment for RIM is generally unsatisfactory, our patient experienced improvement in the pruritus and a regression of the lesions while applying topical 0.1% tacrolimus ointment and 0.1% triamcinolone creme. An early diagnosis of RIM can prevent extensive workup, guide treatment, and improve quality of life for patients. Keywords: radiation-induced morphea, postirradiation morphea

  3. Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth

    Directory of Open Access Journals (Sweden)

    Carlstrom Lucas P

    2011-11-01

    Full Text Available Abstract Background Chemotropic factors in the extracellular microenvironment guide nerve growth by acting on the growth cone located at the tip of extending axons. Growth cone extension requires the coordination of cytoskeleton-dependent membrane protrusion and dynamic adhesion to the extracellular matrix, yet how chemotropic factors regulate these events remains an outstanding question. We demonstrated previously that the inhibitory factor myelin-associated glycoprotein (MAG triggers endocytic removal of the adhesion receptor β1-integrin from the growth cone surface membrane to negatively remodel substrate adhesions during chemorepulsion. Here, we tested how a neurotrophin might affect integrin adhesions. Results We report that brain-derived neurotropic factor (BDNF positively regulates the formation of substrate adhesions in axonal growth cones during stimulated outgrowth and prevents removal of β1-integrin adhesions by MAG. Treatment of Xenopus spinal neurons with BDNF rapidly triggered β1-integrin clustering and induced the dynamic formation of nascent vinculin-containing adhesion complexes in the growth cone periphery. Both the formation of nascent β1-integrin adhesions and the stimulation of axon extension by BDNF required cytoplasmic calcium ion signaling and integrin activation at the cell surface. Exposure to MAG decreased the number of β1-integrin adhesions in the growth cone during inhibition of axon extension. In contrast, the BDNF-induced adhesions were resistant to negative remodeling by MAG, correlating with the ability of BDNF pretreatment to counteract MAG-inhibition of axon extension. Pre-exposure to MAG prevented the BDNF-induced formation of β1-integrin adhesions and blocked the stimulation of axon extension by BDNF. Conclusions Altogether, these findings demonstrate the neurotrophin-dependent formation of integrin-based adhesions in the growth cone and reveal how a positive regulator of substrate adhesions can block

  4. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

    Directory of Open Access Journals (Sweden)

    Neha S. Dole

    2017-11-01

    Full Text Available Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR. Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−, we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.

  5. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.

    Science.gov (United States)

    Dole, Neha S; Mazur, Courtney M; Acevedo, Claire; Lopez, Justin P; Monteiro, David A; Fowler, Tristan W; Gludovatz, Bernd; Walsh, Flynn; Regan, Jenna N; Messina, Sara; Evans, Daniel S; Lang, Thomas F; Zhang, Bin; Ritchie, Robert O; Mohammad, Khalid S; Alliston, Tamara

    2017-11-28

    Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/- ), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Published by Elsevier Inc.

  6. Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

    Science.gov (United States)

    Benoist, David; Dubes, Virginie; Roubertie, François; Gilbert, Stephen H; Charron, Sabine; Constantin, Marion; Elbes, Delphine; Vieillot, Delphine; Quesson, Bruno; Cochet, Hubert; Haïssaguerre, Michel; Rooryck, Caroline; Bordachar, Pierre; Thambo, Jean-Benoit; Bernus, Olivier

    2017-01-01

    Objective The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF). Methods and results Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV. Conclusion Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF. PMID:28051771

  7. Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Takaoki Saneyasu

    2016-01-01

    Full Text Available Tissue and matrix stiffness affect cell properties during morphogenesis, cell growth, differentiation, and migration and are altered in the tissue remodeling following injury and the pathological progression. However, detailed molecular mechanisms underlying alterations of stiffness in vivo are still poorly understood. Recent engineering technologies have developed powerful techniques to characterize the mechanical properties of cell and matrix at nanoscale levels. Extracellular matrix (ECM influences mechanical tension and activation of pathogenic signaling during the development of chronic fibrotic diseases. In this short review, we will focus on the present knowledge of the mechanisms of how ECM stiffness is regulated during the development of liver fibrosis and the molecules involved in ECM stiffness as a potential therapeutic target for liver fibrosis.

  8. 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.

  9. Effect of transcervical resection of adhesion combined with low-dose aspirin on uterine artery blood flow and Smad2/3 in endometrial tissue

    Directory of Open Access Journals (Sweden)

    Qian-Wen Chen

    2016-11-01

    Full Text Available Objective: To study the effect of transcervical resection of adhesion combined with lowdose aspirin on uterine artery blood flow and Smad2/3 in endometrial tissue. Methods: A total of 78 patients with severe intrauterine adhesions who received transcervical resection of adhesion in our hospital between June 2012 and October 2014 were prospectively studied and randomly divided into two groups, observation group received postoperative estrogenprogestogen combined with low-dose aspirin therapy, and control group received postoperative estrogen-progestogen therapy. Ultrasound examination was conducted before and after treatment to determine uterine artery and endometrial blood flow parameters, intrauterine adhesion tissue was collected to detect the expression levels of Smad2 and Smad3 as well as downstream molecules, and serum was collected to determine the levels of cytokines. Results: On the ovulation day after 3 cycles of treatment, uterine artery RI and PI of observation group were significantly lower than those of control group, and endometrial VI, FI and VFI were significantly higher than those of control group; uPA expression level in intrauterine adhesion tissue of observation group was significantly higher than that of control group, Smad2, Smad3, PAI-1, ADAM15 and ADAM17 expression levels were significantly lower than those of control group, and serum TGF-β, VEGF, CTGF, IGF-I and TNF-α levels were significantly lower than those of control group. Conclusions: Transcervical resection of adhesion combined with low-dose aspirin therapy can improve the postoperative uterine artery and endometrial blood flow state, inhibit extracellular matrix deposition mediated by Smad2/3 signaling pathway and prevent intrauterine re-adhesion in patients with intrauterine adhesions.

  10. Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling?

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Søe, Kent; Andersen, Thomas Levin

    2014-01-01

    matrix molecules, collagen's potency was superior and only equaled by fibronectin. Next, the majority of the newly recruited osteoblast lineage cells positioned immediately next to the osteoclasts exhibit uPARAP/Endo180, an endocytic collagen receptor reported to be involved in collagen internalization......Osteoblast recruitment during bone remodeling is obligatory to re-construct the bone resorbed by the osteoclast. This recruitment is believed to be triggered by osteoclast products and is therefore likely to start early during the remodeling cycle. Several osteoclast products with osteoblast...... recruitment potential are already known. Here we draw the attention on the osteoblast recruitment potential of the collagen that is freshly demineralized by the osteoclast. Our evidence is based on observations on adult human cancellous bone, combined with in vitro assays. First, freshly eroded surfaces where...

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

    OpenAIRE

    Nicolae Bacalbasa; Irina Balescu; Alexandru Filipescu

    2018-01-01

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

  12. Factors affecting the outcome of "endometrial scratch" in women with recurrent implantation failure.

    Science.gov (United States)

    Coughlan, Carol; Yuan, Xi; Demirol, Aygul; Ledger, William; Li, Tin Chiu

    2014-01-01

    To examine factors affecting the outcome of the endometrial scratch in women with recurrent implantation failure. A total of 57 eligible patients with a history of recurrent implantation failure underwent an endometrial biopsy in the luteal phase of the menstrual cycle in the month immediately preceding the embryo transfer cycle. The comparative group consisted of a retrospective cohort of 66 women with recurrent implantation failure but without endometrial biopsy. There were no significant differences between the intervention and control groups in terms of age, follicle-stimulating hormone (FSH), free androgen index, anti-Müllerian hormone, body mass index, the number of embryos transferred, and the number of embryo transfer cycles. The clinical pregnancy rate in the intervention group (53%) was significantly (p 10 IU/L. Women with a normal FSH are more likely to derive benefit from endometrial scratch.

  13. Prognostic factors and treatment of endometrial carcinoma

    International Nuclear Information System (INIS)

    Aalders, J.G.

    1982-01-01

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

  14. CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

    OpenAIRE

    Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

    2013-01-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occur...

  15. Smoking Decreases Endometrial Thickness in IVF/ICSI Patients.

    Science.gov (United States)

    Heger, Anna; Sator, Michael; Walch, Katharina; Pietrowski, Detlef

    2018-01-01

    Smoking is a serious problem for the health care system. Many of the compounds identified in cigarette smoke have toxic effects on the fertility of both females and males. The purpose of this study was to determine whether smoking affects clinical factors during IVF/ICSI therapy in a single-center reproductive unit. In a retrospective study of 200 IVF/ICSI cycles, endometrial thickness and the outcome of IVF/ICSI therapy were analyzed. Endometrial thickness was significantly lower in smoking patients than in non-smoking patients (10.4 ± 1.5 mm vs. 11.6 ± 1.8 mm). Age was significantly higher in women who failed to conceive. The total dose of gonadotropins administered was significantly lower in pregnant patients and the highest pregnancy rate was achieved with an rFSH protocol. BMI and number of cigarettes smoked did not influence treatment outcomes in this study. We showed that smoking has a negative effect on endometrial thickness on the day of embryo transfer. This may help to further explain the detrimental influence of tobacco smoke on implantation and pregnancy rates during assisted reproduction therapy.

  16. Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia.

    Science.gov (United States)

    Asyikeen, Wan Adnan Wan Nor; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Zin, Anani Aila Mat; Othman, Nor Hayati

    2016-11-01

    Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.

  17. Staging in local endometrial carcinoma

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Paul H van der Horst

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

  20. Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Lianlian Wang

    2015-07-01

    Full Text Available Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR: 0.77, 95% CI: 0.62–0.96, I2: 63.0%, especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95. A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99. Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk.

  1. Matrix metalloproteinase 2 genotype is associated with nonanastomotic biliary strictures after orthotopic liver transplantation

    NARCIS (Netherlands)

    Ten Hove, W. Rogier; Korkmaz, Kerem S.; den Dries, Sanna Op; de Rooij, Bert-Jan F.; van Hoek, Bart; Porte, Robert J.; van der Reijden, Johan J.; Coenraad, Minneke J.; Dubbeld, Jeroen; Hommes, Daniel W.; Verspaget, Hein W.

    Background: Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are involved in connective tissue remodelling in chronic liver disease and complications after OLT. Aim: To evaluate the relationship between

  2. Concomitant hysteroscopic endometrial ablation and Essure procedure: feasibility, efficacy and satisfaction.

    Science.gov (United States)

    Levy-Zauberman, Y; Legendre, G; Nazac, A; Faivre, E; Deffieux, X; Fernandez, H

    2014-07-01

    Hysteroscopic endometrial destruction procedures for abnormal uterine bleeding are an alternative to hysterectomy. Such procedures are not contraceptive and are performed on fertile patients, requiring long-term contraception. This is the first study evaluating long-term results of a combined procedure associating endometrial destruction and concomitant hysteroscopic tubal sterilization by Essure(®) micro-inserts. Our goal is to evaluate efficacy of endometrial destruction as well as hysteroscopic sterilization and satisfaction after a combined procedure in the case of abnormal uterine bleeding in non-menopausal patients. This is a retrospective study (Canadian task force II-2) that includes 131 patients operated with combined endometrial destruction and hysteroscopic tubal sterilization between 2002 and 2011 at our university hospital. The patients were contacted to answer a questionnaire. Statistical analysis was performed with SAS© version 9.2. (SAS Institute Inc., Cary, NC). Ninety-three patients out of 131 could be reached. The mean follow-up was of 37.8 months (min=8, max=87, SD=6.2). Thirty-eight patients (29%) were lost to follow-up. Essure(®) micro-inserts introduction success rate (evaluated on 131 patients) was 95.8%, and their position was appropriate in 81.1% of the 106 patients with position control. Efficacy of the procedure on the haemorrhagic symptoms (evaluated on 93 patients) was 80.6%. Twelve patients (12.9%) underwent a hysterectomy, 7 of which (58.3%) were a direct consequence of treatment failure. No pregnancies were reported. Satisfaction rate was of 90.3%. Inadequate position rates of the micro-inserts after 3 months seem somewhat above literature findings, though no pregnancy has been reported. However, recurrent bleeding symptoms and hysterectomy rates are consistent with those observed after an endometrial destruction procedure alone. Limitations are the limited number of patients, the bias inherent to retrospective studies (lost of

  3. Serosal and Endometrial Reconstitution During Myomectomy ...

    African Journals Online (AJOL)

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

  4. Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation.

    Science.gov (United States)

    Maybin, Jacqueline A; Murray, Alison A; Saunders, Philippa T K; Hirani, Nikhil; Carmeliet, Peter; Critchley, Hilary O D

    2018-01-23

    Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.

  5. Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities.

    Science.gov (United States)

    Ganjam, V K; Evans, T J

    2006-03-27

    Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-beta1 resulting in myofibroblastic transformation. 11Beta-HSD2 in concert appears to modulate the severity of endometrial fibrosis.

  6. Cadmium exposure and endometrial cancer risk: A large midwestern U.S. population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Jane A McElroy

    Full Text Available Estrogen-mimicking chemicals, such as cadmium, may be associated with increased susceptibility to hormone-dependent cancers, though supporting data are sparse, particularly for endometrial cancer. The Health and Environmental Exposure Research (HEER study worked with the Arkansas Central Cancer Registry, Iowa Cancer Registry and Missouri Cancer Registry to obtain names of women diagnosed with endometrial cancer who were willing to be contacted for participation in our case control study. Voter registration lists from Iowa and Missouri were used to randomly select similarly aged women as represented in the case population. Participants were interviewed by telephone to obtain information on known or suspected endometrial risk factors. Urine kits were sent to participants for home collection and returned for analysis. Our case-control study consisted of 631 incident cases of endometrial cancer diagnosed from January 2010 to October 2012 and 879 age-matched population-based controls, ages 18-81 years (mean age 65 years. We quantified cadmium amounts in urine and standardized these values through creatinine adjustment. Using data from all survey completers, we developed a multivariable model for endometrial cancer. Creatinine-adjusted cadmium concentration was added to this model. Odds ratio (OR and 95% confidence intervals (CIs for endometrial cancer were calculated. After multivariable adjustment, higher creatinine-adjusted cadmium exposure was associated with a statistically significant increase of endometrial cancer risk (OR: 1.22; 95% CI: 1.03-1.44. Our results provide evidence that cadmium may increase the risk of endometrial cancer, possibly through estrogenic effects.

  7. Arterial grafts exhibiting unprecedented cellular infiltration and remodeling in vivo: the role of cells in the vascular wall.

    Science.gov (United States)

    Row, Sindhu; Peng, Haofan; Schlaich, Evan M; Koenigsknecht, Carmon; Andreadis, Stelios T; Swartz, Daniel D

    2015-05-01

    To engineer and implant vascular grafts in the arterial circulation of a pre-clinical animal model and assess the role of donor medial cells in graft remodeling and function. Vascular grafts were engineered using Small Intestinal Submucosa (SIS)-fibrin hybrid scaffold and implanted interpositionally into the arterial circulation of an ovine model. We sought to demonstrate implantability of SIS-Fibrin based grafts; examine the remodeling; and determine whether the presence of vascular cells in the medial wall was necessary for cellular infiltration from the host and successful remodeling of the implants. We observed no occlusions or anastomotic complications in 18 animals that received these grafts. Notably, the grafts exhibited unprecedented levels of host cell infiltration that was not limited to the anastomotic sites but occurred through the lumen as well as the extramural side, leading to uniform cell distribution. Incoming cells remodeled the extracellular matrix and matured into functional smooth muscle cells as evidenced by expression of myogenic markers and development of vascular reactivity. Interestingly, tracking the donor cells revealed that their presence was beneficial but not necessary for successful grafting. Indeed, the proliferation rate and number of donor cells decreased over time as the vascular wall was dominated by host cells leading to significant remodeling and development of contractile function. These results demonstrate that SIS-Fibrin grafts can be successfully implanted into the arterial circulation of a clinically relevant animal model, improve our understanding of vascular graft remodeling and raise the possibility of engineering mural cell-free arterial grafts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 17β-Hydroxysteroid Dehydrogenase Type 2 Expression Is Induced by Androgen Signaling in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Chiaki Hashimoto

    2018-04-01

    Full Text Available Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2, which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT was found to induce 17β-HSD2 mRNA and protein expression in HEC-1B endometrial cancer cells. DHT could also inhibit cell proliferation of HEC-1B when induced by estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA tissues, intratumoral DHT concentration was measured by liquid chromatography/electrospray tandem mass spectrometry and was found to be significantly correlated with 17β-HSD2 immunohistochemical status. We further examined the correlations between 17β-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA tissues. 17β-HSD2 status was inversely associated with the histological grade, clinical stage, and cell proliferation marker Ki-67, and positively correlated with progesterone receptor expression. 17β-HSD2 status tended to be positively associated with androgen receptor status. In 53 EEA cases, the 17β-HSD2-positive group tended to have better prognosis than that for the negative group with respect to progression-free survival and endometrial cancer-specific survival. These findings suggest that androgen suppresses the estrogen dependence of endometrial cancer through the induction of 17β-HSD2 in endometrial cancer.

  9. Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

    Directory of Open Access Journals (Sweden)

    Cymbaluk-Ploska A

    2017-06-01

    Full Text Available Aneta Cymbaluk-Płoska,1 Anita Chudecka-Głaz,1 Ewa Pius-Sadowska,2 Agnieszka Sompolska-Rzechuła,3 Bogusław Machaliński,2 Anna Surowiec,1 Janusz Menkiszak1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, 2Department of General Pathology, Pomeranian Medical University, 3Department of Statistics, West Pomeranian University of Technology, Szczecin, Poland Introduction: Endometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.Aim: To explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methods: Included in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA. MMP2 concentrations were quantified in the serum using multiplex immunoassays.Results: We observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003. The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV vs low (FIGO I and II clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3 on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre

  10. Office hysteroscopy, transvaginal ultrasound and endometrial histology: a comparison in infertile patients

    Directory of Open Access Journals (Sweden)

    Devleta Balić

    2011-05-01

    Full Text Available Objective. To evaluate accuracy of transvaginal sonography (TVS and hysteroscopy in detection of intrauterine pathology in infertile women. Subjects and methods. This retrospective study was conducted in 56 infertile women with abnormal transvaginal ultrasound findings of the uterine cavity which was performed during the midfollicular phase as a part of routine infertility workup. Hysteroscopy was performed between 6th and 10th day of cycle. Results. The mean age of the subjects was 31.9±4.0. The most frequent ultrasound finding was endometrial polyp in 34 (60.7% patients, septate uterus in 8 (14.3% patients, submucosal myoma in 7 (12.5% patients, endometrial hyperplasia in 5 (8.9% patients and Syndroma Ascherman in 2 (3.6% patients. Hysteroscopy confirmed 20 (35.7% polyps, the same number of myomas, septate uterus and Syndroma Ascherman as detected by ultrasound, (7 (12.5%, 8 (14.3% and 2 (3.6%, respectively and 19 (33.9% endometrial hyperplasia. In 46 women with histological excamination, the sensitivity of TVS and hysteroscopy in the diagnosis of endometrial polyps were identical - 100%, while the specificity was higher in hysteroscopy than in TVS (92.3% versus 56.4%, p<0.001. The sensitivity of TVS in the diagnosis of endometrial hyperplasia was higher than that of hysteroscopy (86.4% versus 22.7%, p<0.001, while specificity was identical, of 100%. Accordance between hysteroscopy and histology was good (k=0.79, between ultrasound and histology was moderete (k=0.59. Conclusion. Hysteroscopy appeared to be more reliable in diagnosis than TVS. The use of a high frequency ultrasound probe leads us to a lack of diagnostic clarity between endometrial polyps and hyperplasia.

  11. morphological pattern of endometrial biopsies in south

    African Journals Online (AJOL)

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

  12. Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling

    Directory of Open Access Journals (Sweden)

    Priscilla Ludovico da Silva

    2015-12-01

    Full Text Available The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

  13. Impact of robotics on the outcome of elderly patients with endometrial cancer.

    Science.gov (United States)

    Lavoue, Vincent; Zeng, Xing; Lau, Susie; Press, Joshua Z; Abitbol, Jeremie; Gotlieb, Raphael; How, Jeffrey; Wang, Yifan; Gotlieb, Walter H

    2014-06-01

    To evaluate the impact of introducing a robotics program on clinical outcome of elderly patients with endometrial cancer. Evaluation and comparison of peri-operative morbidity and disease-free interval in 163 consecutive elderly patients (≥70years) with endometrial cancer undergoing staging procedure with traditional open surgery compared to robotic surgery. All consecutive patients ≥70years of age with endometrial cancer who underwent robotic surgery (n=113) were compared with all consecutive patients ≥70years of age (n=50) before the introduction of a robotic program in December 2007. Baseline patient characteristics were similar in both eras. Patients undergoing robotic surgery had longer mean operating times (244 compared with 217minutes, p=0.009) but fewer minor adverse events (17% compared with 60%, probotics cohort had less estimated mean blood loss (75 vs 334mL, probotics program for the treatment of endometrial cancer in the elderly has significant benefits, including lower minor complication rate, less operative blood loss and shorter hospitalization without compromising 2-year disease-free survival. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Preservation of the endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound ablation of submucosal uterine fibroids

    International Nuclear Information System (INIS)

    Kim, Young-sun; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Lim, Hyo Keun; Rhim, Hyunchul; Jung, Sin-Ho; Ahn, Joong Hyun

    2017-01-01

    To evaluate the integrity of endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) ablation of submucosal uterine fibroids based on contrast-enhanced MRI findings, and to identify the risk factors for endometrial impairment. In total, 117 submucosal fibroids (diameter: 5.9 ± 3.0 cm) in 101 women (age: 43.6 ± 4.4 years) treated with MR-HIFU ablation were retrospectively analysed. Endometrial integrity was assessed with contrast-enhanced T1-weighted images at immediate (n = 101), 3-month (n = 62) and 12-month (n = 15) follow-ups. Endometrial impairment was classified into grades 0 (continuous endometrium), 1 (pin-point, full-thickness discontinuity), 2 (between grade 1 and 3), or 3 (full-thickness discontinuity >1 cm). Risk factors were assessed with generalized estimating equation (GEE) analysis. Among 117 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed at initial examination in 56.4%, 24.8%, 13.7% and 4.3%, respectively. Among 37 fibroid cases of endometrial impairment for which follow-ups were conducted, 30 showed improvements at 3- and/or 12-month follow-up. GEE analysis revealed the degree of endometrial protrusion was significantly associated with severity of endometrial injury (P < 0.0001). After MR-HIFU ablation of submucosal fibroids, endometrial enhancement was preserved intact or minimally impaired in most cases. Impaired endometrium, which is more common after treating endometrially-protruded fibroids, may recover spontaneously. (orig.)

  15. Preservation of the endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound ablation of submucosal uterine fibroids

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-sun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Uterine Fibroid Integrated Management Center, MINT Intervention Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of); Lim, Hyo Keun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); SAIHST, Sungkyunkwan University, Department of Health Sciences and Technology, Seoul (Korea, Republic of); Rhim, Hyunchul [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Jung, Sin-Ho [SAIHST, Sungkyunkwan University, Department of Health Sciences and Technology, Seoul (Korea, Republic of); Samsung Medical Center, Department of Biostatistics and Clinical Epidemiology, Seoul (Korea, Republic of); Ahn, Joong Hyun [Samsung Biomedical Research Institute, Samsung Medical Center, Biostatistics Team, Seoul (Korea, Republic of)

    2017-09-15

    To evaluate the integrity of endometrial enhancement after magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) ablation of submucosal uterine fibroids based on contrast-enhanced MRI findings, and to identify the risk factors for endometrial impairment. In total, 117 submucosal fibroids (diameter: 5.9 ± 3.0 cm) in 101 women (age: 43.6 ± 4.4 years) treated with MR-HIFU ablation were retrospectively analysed. Endometrial integrity was assessed with contrast-enhanced T1-weighted images at immediate (n = 101), 3-month (n = 62) and 12-month (n = 15) follow-ups. Endometrial impairment was classified into grades 0 (continuous endometrium), 1 (pin-point, full-thickness discontinuity), 2 (between grade 1 and 3), or 3 (full-thickness discontinuity >1 cm). Risk factors were assessed with generalized estimating equation (GEE) analysis. Among 117 fibroids, grades 0, 1, 2 and 3 endometrial impairments were observed at initial examination in 56.4%, 24.8%, 13.7% and 4.3%, respectively. Among 37 fibroid cases of endometrial impairment for which follow-ups were conducted, 30 showed improvements at 3- and/or 12-month follow-up. GEE analysis revealed the degree of endometrial protrusion was significantly associated with severity of endometrial injury (P < 0.0001). After MR-HIFU ablation of submucosal fibroids, endometrial enhancement was preserved intact or minimally impaired in most cases. Impaired endometrium, which is more common after treating endometrially-protruded fibroids, may recover spontaneously. (orig.)

  16. Glycogen Synthase Kinase 3β Inhibition as a Therapeutic Approach in the Treatment of Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Liang Ma

    2013-08-01

    Full Text Available Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3β (GSK3β, and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3β inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3β by either lithium chloride (LiCl or specific GSK3β inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952 and type II (ARK1 endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3β activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth.

  17. Long-Term Outcome and Quality of Life of Patients With Endometrial Carcinoma Treated With or Without Pelvic Radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) Trial

    NARCIS (Netherlands)

    Nout, Remi A.; van de Poll-Franse, Lonneke V.; Lybeert, Marnix L. M.; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Mens, Jan Willem M.; Lutgens, Ludy C. H. W.; Pras, Betty; van Putten, Wim L. J.; Creutzberg, Carien L.

    2011-01-01

    Purpose To determine the long-term outcome and health-related quality of life (HRQL) of patients with endometrial carcinoma (EC) treated with or without pelvic radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial. Patients and Methods Between 1990 and

  18. Endometrial Histology of Depomedroxyprogesterone Acetate Users: A Pilot Study

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Objective. To obtain pilot data on the endometrial histology of Depomedroxyprogesterone acetate (Depo-Provera, DMPA users experiencing breakthrough bleeding (BTB versus users with amenorrhea. To compare the endometrial histology of patients who used DMPA continuously for 3–12 months versus those who used it for 13 months or more. Methods. Cross-sectional study. Endometrial biopsy was obtained from all consenting patients who used DMPA for at least 3 months. Patients were divided into those with BTB in the last 3 months versus those with amenorrhea for at least 3 months. Histology results and duration of therapy were compared. Results. The proportion of women with chronic endometritis, uterine polyps, atrophic, proliferative, or progesterone-dominant endometrium did not differ between those DMPA users with BTB versus those with amenorrhea. Duration of therapy did not correlate with symptoms of BTB or endometrial histology. Chronic endometritis was the most common histologic finding (10/40, 25% and occurred more often in women experiencing BTB (35% versus 15% (RR 1.62 CI 0.91–2.87. Moreover, 45% of women with BTB had received DMPA for more than 12 months. Conclusions. BTB was more common than previously reported in women using DMPA for more than 12 months. Chronic endometritis, which may indicate an underlying infectious or intracavitary anatomic etiology, has not been previously reported as a frequent finding in DMPA users, and may be related to ethnic or other sociodemographic characteristics of our patient population. Further study to elucidate the etiology of chronic endometritis in these patients is warranted.

  19. Development and validation of prediction models for endometrial cancer in postmenopausal bleeding.

    Science.gov (United States)

    Wong, Alyssa Sze-Wai; Cheung, Chun Wai; Fung, Linda Wen-Ying; Lao, Terence Tzu-Hsi; Mol, Ben Willem J; Sahota, Daljit Singh

    2016-08-01

    To develop and assess the accuracy of risk prediction models to diagnose endometrial cancer in women having postmenopausal bleeding (PMB). A retrospective cohort study of 4383 women in a One-stop PMB clinic from a university teaching hospital in Hong Kong. Clinical risk factors, transvaginal ultrasonic measurement of endometrial thickness (ET) and endometrial histology were obtained from consecutive women between 2002 and 2013. Two models to predict risk of endometrial cancer were developed and assessed, one based on patient characteristics alone and a second incorporated ET with patient characteristics. Endometrial histology was used as the reference standard. The split-sample internal validation and bootstrapping technique were adopted. The optimal threshold for prediction of endometrial cancer by the final models was determined using a receiver-operating characteristics (ROC) curve and Youden Index. The diagnostic gain was compared to a reference strategy of measuring ET only by comparing the AUC using the Delong test. Out of 4383 women with PMB, 168 (3.8%) were diagnosed with endometrial cancer. ET alone had an area under curve (AUC) of 0.92 (95% confidence intervals [CIs] 0.89-0.94). In the patient characteristics only model, independent predictors of cancer were age at presentation, age at menopause, body mass index, nulliparity and recurrent vaginal bleeding. The AUC and Youdens Index of the patient characteristic only model were respectively 0.73 (95% CI 0.67-0.80) and 0.72 (Sensitivity=66.5%; Specificity=68.9%; +ve LR=2.14; -ve LR=0.49). ET, age at presentation, nulliparity and recurrent vaginal bleeding were independent predictors in the patient characteristics plus ET model. The AUC and Youdens Index of the patient characteristic plus ET model where respectively 0.92 (95% CI 0.88-0.96) and 0.71 (Sensitivity=82.7%; Specificity=88.3%; +ve LR=6.38; -ve LR=0.2). Comparison of AUC indicated that a history alone model was inferior to a model using ET alone

  20. 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...

  1. 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...

  2. 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...

  3. Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer.

    Science.gov (United States)

    Shafiee, Mohamad N; Mongan, Nigel; Seedhouse, Claire; Chapman, Caroline; Deen, Suha; Abu, Jafaru; Atiomo, William

    2017-05-01

    Women with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m 2 ) and controls (28.58 ± 2.62 kg/m 2 ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m 2 ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r = 0.643, p = 0.06) and waist-hip ratio (r = 0.096, p = 0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p = 0.028 and p = 0.027, respectively). Quantitative serum sterol regulatory element

  4. FIFTEEN-YEAR RADIOTHERAPY OUTCOMES OF THE RANDOMIZED PORTEC-1 TRIAL FOR ENDOMETRIAL CARCINOMA

    NARCIS (Netherlands)

    Creutzberg, Carien L.; Nout, Remi A.; Lybeert, Marnix L. M.; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Mens, Jan-Willem M.; Lutgens, Ludy C. H. W.; Pras, Elisabeth; van de Poll-Franse, Lonneke V.; van Putten, Wim L. J.

    2011-01-01

    Purpose: To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second

  5. SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients

    DEFF Research Database (Denmark)

    Antonsen, Sofie Leisby; Loft, Annika; Fisker, Rune Vincents

    2013-01-01

    OBJECTIVE: To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS: A total of 268 women with endometrial cancer or atypical...... endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS: SUVmax was significantly higher in patients with high FIGO stages (p...

  6. Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis.

    Science.gov (United States)

    Kyama, Cleophas M; Mihalyi, Attila; Simsa, Peter; Falconer, Henrik; Fulop, Vilmos; Mwenda, Jason M; Peeraer, Karen; Tomassetti, Carla; Meuleman, Christel; D'Hooghe, Thomas M

    2009-06-01

    A clear picture of the dynamic relationship between the endometrium and peritoneum is emerging as both tissues may participate in the spontaneous development of endometriosis. Various adhesion molecules, pro-inflammatory cytokines and chemoattractants cytokines have emerged as central coordinators of endometrial-peritoneal interactions. The peritoneal microenvironment which consists of the peritoneal fluid, normal peritoneum and peritoneal endometriotic lesions may play an active role in the pathogenesis of endometriosis, by harbouring most inflammatory responses that are triggered by the presence of endometrial cells, leading to recruitment of activated macrophages and leukocytes locally. Menstrual endometrium has the ability to bond and invade the peritoneal tissue. In baboons intrapelvic injection of menstrual endometrium permits the study of early endometrial-peritoneal interaction in an in vivo culture microenvironment and can lead to important insight in the early development of endometriotic lesions. In this review, we discuss the roles of the endometrial-peritoneal interactions, not only in disease development but also in the broader process of aetiopathogenesis.

  7. Endometrial carcinoma: merit of magnetic resonance in pre-surgical staging

    International Nuclear Information System (INIS)

    Fernandez, E.; Barrera, M. C.; Gervas, C.; Salvador, E.; Rivero, B.; Sentis, M.

    2003-01-01

    To evaluate MR capacity in assessing deep myometrial and cervical infiltrations in cases of endometrial carcinoma. A series of 30 consecutively diagnosed endometrial cancer patients was pre-surgically evaluated by means of magnetic resonance (MR). TSE-T2 sequences with fat saturation and dynamic FFe sequence were used after gadolinium administration. A correlation with post-surgical histological stating was made. There were then determined sensitivity (S), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the deep myometrial infiltration and cervical invasion. Cases of overestimation and underestimation were analyzed. Values obtained for myometrium and cervix were, respectively, S of 67% and 63%, SP of 89% and 91%, PPV of 80% and 71% and NPV of 80% and 87%. Two cases each were over valued for myometrial infiltration and cervix: four cases and 3 cases, respectively, were undervalues. MR stating in cases of endometrial carcinoma is a highly reliable diagnostic technique, but it does present certain limitations. (Author) 19 refs

  8. Histopathology-like categories based on endometrial imprint cytology in dysfunctional uterine bleeding.

    Science.gov (United States)

    Baxi, Seema N; Panchal, Nirav S

    2015-01-01

    Cytology of the endometrium is an underused technique in diagnostic pathology. It has been used in the past for endometrial hyperplasia and carcinoma. Only few studies have used cytology in the diagnosis of dysfunctional uterine bleeding (DUB). Endometrial imprint cytology has been rarely used except for application of immunocytochemistry in diagnosis of endometrial carcinoma. The present study was conducted to evaluate whether it is possible to assign histopathology-like diagnosis by imprint cytology and also to evaluate its usefulness in the assessment of patients of dysfunctional uterine bleeding of low clinical suspicion. Imprint smears were made from 93 curettage materials during a study of DUB. Blinded analysis of imprint smears was performed by using McKenzie's criteria and some criteria devised for the requirements of this study. Results of cytology were correlated with histopathology. Statistical analysis was carried out by GraphpadInStat Demo. Majority of the patterns classifiable in histopathology could also be classified in this study on imprint cytology. The overall sensitivity and specificity of cytology in the detection of endometrial patterns in DUB patients were 91.23% and 83.87%, respectively, although the sensitivities and specificities differ according to the phase of endometrium. Histopathology-like categories can be assigned on imprint smears in the diagnosis of DUB. Endometrial imprint cytology can be helpful in centers where histopathology laboratories are not available and even in well-established institutes. It is possible to improve the sensitivity and specificity with better imprinting techniques.

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

    Directory of Open Access Journals (Sweden)

    Milosz Wilczynski

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

  10. Detection of Matrix Metalloproteinases by Zymography.

    Science.gov (United States)

    Tajhya, Rajeev B; Patel, Rutvik S; Beeton, Christine

    2017-01-01

    Matrix metalloproteinases (MMPs) represent more than 20 zinc-containing endopeptidases that cleave internal peptide bonds, leading to protein degradation. They play a critical role in many physiological cell functions, including tissue remodeling, embryogenesis, and angiogenesis. They are also involved in the pathogenesis of a vast array of diseases, including but not limited to systemic inflammation, various cancers, and cardiovascular, neurological, and autoimmune diseases. Here, we describe gel zymography to detect MMPs in cell and tissue samples and in cell culture supernatants.

  11. Serotonin receptor 2B signaling with interstitial cell activation and leaflet remodeling in degenerative mitral regurgitation.

    Science.gov (United States)

    Driesbaugh, Kathryn H; Branchetti, Emanuela; Grau, Juan B; Keeney, Samuel J; Glass, Kimberly; Oyama, Mark A; Rioux, Nancy; Ayoub, Salma; Sacks, Michael S; Quackenbush, John; Levy, Robert J; Ferrari, Giovanni

    2018-02-01

    Mitral valve interstitial cells (MVIC) play an important role in the pathogenesis of degenerative mitral regurgitation (MR) due to mitral valve prolapse (MVP). Numerous clinical studies have observed serotonin (5HT) dysregulation in cardiac valvulopathies; however, the impact of 5HT-mediated signaling on MVIC activation and leaflet remodeling in MVP have been investigated to a limited extent. Here we test the hypothesis that 5HT receptors (5HTRs) signaling contributes to MVP pathophysiology. Diseased human MV leaflets were obtained during cardiac surgery for MVP; normal MV leaflets were obtained from heart transplants. MV RNA was used for microarray analysis of MVP patients versus control, highlighting genes that indicate the involvement of 5HTR pathways and extracellular matrix remodeling in MVP. Human MV leaflets were also studied in vitro and ex vivo with biomechanical testing to assess remodeling in the presence of a 5HTR2B antagonist (LY272015). MVP leaflets from Cavalier King Charles Spaniels were used as a naturally acquired in vivo model of MVP. These canine MVP leaflets (N=5/group) showed 5HTR2B upregulation. This study also utilized CB57.1ML/6 mice in order to determine the effect of Angiotensin II infusion on MV remodeling. Histological analysis showed that MV thickening due to chronic Angiotensin II remodeling is mitigated by a 5HTR2B antagonist (LY272015) but not by 5HTR2A inhibitors. In humans, MVP is associated with an upregulation in 5HTR2B expression and increased 5HT receptor signaling in the leaflets. Antagonism of 5HTR2B mitigates MVIC activation in vitro and MV remodeling in vivo. These observations support the view that 5HTR signaling is involved not only in previously reported 5HT-related valvulopathies, but it is also involved in the pathological remodeling of MVP. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator.

    Science.gov (United States)

    Ioffe, Olga B; Zaino, Richard J; Mutter, George L

    2009-03-01

    Selective progesterone receptor modulators are a class of drugs with progesterone antagonist activity that may confer therapeutic benefit for reproductive disorders in premenopausal women. Endometrial structure, which is dynamically controlled by circulating sex hormones, is likely to be perturbed by progesterone receptor modulators through their progesterone antagonist properties. We examined endometrial histology in 58 premenopausal women treated with the progesterone receptor modulator CDB-4124 (also known as Proellex) for endometriosis or uterine leiomyomata in two clinical trials. Endometrial biopsies obtained after 3 or 6 months with doses of 12.5, 25, or 50 mg daily oral CDB-4124 were reviewed independently by three pathologists. Consensus diagnoses using the World Health Organization hyperplasia scoring system, comments on specific histologic features, and clinical annotation were collected and analyzed. The majority of the endometrial biopsies (103 of 174 biopsies) contained histologic changes that are not seen during normal menstrual cycles. The histology of CDB-4124-treated patients was generally inactive or atrophic, and less frequently, proliferative or secretory, superimposed upon which were novel changes including formation of cystically dilated glands, and secretory changes coexisting with mitoses and apoptotic bodies. With increasing treatment dose and duration, the cysts became predominant and their lining inactive or atrophic. Cystic glands in the CDB-4124-treated subjects correlated with increased endometrial thickness by ultrasound. None of the CDB-4124-treated patients developed endometrial carcinoma or hyperplasia while on therapy. CDB-4124 therapy for 3-6 months produces histologic changes that are sufficiently novel that they might easily be misinterpreted by pathologists, particularly as disordered proliferative or hyperplastic endometrium. Knowledge of the constellation of endometrial changes associated with this agent and other

  13. Endometrial adenocarcinoma arising in a Turner's syndrome patient with spontaneous menstruation: a case report.

    Science.gov (United States)

    Sasamoto, Naoko; Ueda, Yutaka; Amemiya, Kyoka; Enomoto, Takayuki; Morii, Eiichi; Adachi, Kazushige

    2014-01-01

    Women with Turner's syndrome exhibit anovulation, and the majority do not spontaneously menstruate. We present an unusual case of endometrial adenocarcinoma developing in a Turner's syndrome patient who was exhibiting spontaneous menstruation while not receiving regular hormone therapy. The patient's karyotype from blood lymphocytes was a mosaic of 45,XO/ 46,XX. Menarche and sexual development were normal. Her menstrual cycle had been regular for one year, but then became noticeably irregular. At age 26 she was referred to our hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was detected during performance of diagnostic endometrial curettage. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy was conducted. The final histological diagnosis was endometrial adenocarcinoma, Grade 1, pT1a N0 M0. Fluorescence in situ hybridization analysis of the right and left ovaries revealed a mosaic karyotype of 45,XO/ CONCLUSION: Previous reports regarding Turner's syndrome detected spontaneous menstruation in only 16% of patients; however, spontaneous menstruation was observed in 8 of 10 (80%) Turner's syndrome cases that developed endometrial carcinoma without receiving regular hormone therapy (p < 0.0001). Hormone therapy may be indicated for an irregular menstrual cycle in Turner's syndrome patients.

  14. A prospective investigation of fish, meat and cooking-related carcinogens with endometrial cancer incidence.

    Science.gov (United States)

    Arem, H; Gunter, M J; Cross, A J; Hollenbeck, A R; Sinha, R

    2013-08-06

    There are limited prospective studies of fish and meat intakes with risk of endometrial cancer and findings are inconsistent. We studied associations between fish and meat intakes and endometrial cancer incidence in the large, prospective National Institutes of Health-AARP Diet and Health Study. Intakes of meat mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP) were also calculated. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed no associations with endometrial cancer risk comparing the highest to lowest intake quintiles of red (HR=0.91, 95% CI 0.77-1.08), white (0.98, 0.83-1.17), processed meats (1.02, 0.86-1.21) and fish (1.10, 95% CI 0.93-1.29). We also found no associations between meat mutagen intakes and endometrial cancer. Our findings do not support an association between meat or fish intakes or meat mutagens and endometrial cancer.

  15. Fibroblasts and the extracellular matrix in right ventricular disease.

    Science.gov (United States)

    Frangogiannis, Nikolaos G

    2017-10-01

    Right ventricular failure predicts adverse outcome in patients with pulmonary hypertension (PH), and in subjects with left ventricular heart failure and is associated with interstitial fibrosis. This review manuscript discusses the cellular effectors and molecular mechanisms implicated in right ventricular fibrosis. The right ventricular interstitium contains vascular cells, fibroblasts, and immune cells, enmeshed in a collagen-based matrix. Right ventricular pressure overload in PH is associated with the expansion of the fibroblast population, myofibroblast activation, and secretion of extracellular matrix proteins. Mechanosensitive transduction of adrenergic signalling and stimulation of the renin-angiotensin-aldosterone cascade trigger the activation of right ventricular fibroblasts. Inflammatory cytokines and chemokines may contribute to expansion and activation of macrophages that may serve as a source of fibrogenic growth factors, such as transforming growth factor (TGF)-β. Endothelin-1, TGF-βs, and matricellular proteins co-operate to activate cardiac myofibroblasts, and promote synthesis of matrix proteins. In comparison with the left ventricle, the RV tolerates well volume overload and ischemia; whether the right ventricular interstitial cells and matrix are implicated in these favourable responses remains unknown. Expansion of fibroblasts and extracellular matrix protein deposition are prominent features of arrhythmogenic right ventricular cardiomyopathies and may be implicated in the pathogenesis of arrhythmic events. Prevailing conceptual paradigms on right ventricular remodelling are based on extrapolation of findings in models of left ventricular injury. Considering the unique embryologic, morphological, and physiologic properties of the RV and the clinical significance of right ventricular failure, there is a need further to dissect RV-specific mechanisms of fibrosis and interstitial remodelling. Published on behalf of the European Society of

  16. Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

    Science.gov (United States)

    Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

    2015-06-01

    Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs. Copyright © 2015 the American Physiological Society.

  17. Survival after relapse in patients with endometrial cancer : results from a randomized trial

    NARCIS (Netherlands)

    Creutzberg, CL; van Putten, WLJ; Koper, PC; Lybeert, MLM; Jobsen, JJ; Warlam-Rodenhuis, CC; De Winter, KAJ; Lutgens, LCHW; van den Bergh, ACM; van der Steen-Banasik, E; Beerman, H; van Lent, M

    Objective. The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. Methods, The PORTEC trial included 715 patients with stage I endometrial cancer, either grade I or 2

  18. Endometrial aspiration biopsy: a non-invasive method of obtaining functional lymphoid progenitor cells and mature natural killer cells.

    LENUS (Irish Health Repository)

    McMenamin, Moya

    2012-09-01

    The aim of this study was to compare the efficacy of endometrial aspiration biopsy (EAB) with the more traditional dilatation and curettage (D&C) for the procurement of lymphoid progenitor cells and uterine natural killer (NK) populations in endometrial tissue. This prospective observational study conducted in a tertiary referral university hospital examined endometrium obtained from 32 women admitted for laparoscopic gynaecological procedures. Each participant had endometrium sampled using both EAB and D&C. Both methods were assessed as a source of uterine NK and lymphoid progenitor cells. Similar proportions of mature CD45+CD56+ NK cells (range 25.4-36.2%) and CD45+CD34+ lymphoid progenitors (range 1.2-2.0%) were found in tissue obtained using both EAB and D&C. These cells were adequate for flow cytometric analysis, magnetic bead separation and culture. Colony formation by the CD34+ population demonstrated maturational potential. Tissues obtained via endometrial biopsy and D&C are equivalent, by analysis of uterine NK and lymphoid progenitor cells. The aim of this study was to compare two methods of endometrial sampling - endometrial aspiration biopsy and traditional dilatation and curettage - for the procurement of haematopoietic stem cells and uterine natural killer (NK) populations in endometrial tissue. Thirty-two women who had gynaecological procedures in a tertiary referral hospital participated in this study and had endometrial tissue collected via both methods. Similar populations of mature NK cells and haematopoietic stem cells were found in tissue obtained using both endometrial aspiration biopsy and dilatation and curettage. Tissue obtained via endometrial aspiration biopsy was adequate for the culture and growth of haematopoietic stem cells. We conclude that tissue obtained via endometrial biopsy and dilatation and curettage is equivalent, by analysis of uterine NK and haematopoietic stem cells using flow cytometry. This has implications for further

  19. A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis

    DEFF Research Database (Denmark)

    Nastic, Denis; Shanwell, Emma; Wallin, Keng-Ling

    2017-01-01

    Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown...... that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53...

  20. 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...

  1. Molecular Biology and Prevention of Endometrial Cancer. Addendum

    National Research Council Canada - National Science Library

    Maxwell, George L

    2008-01-01

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

  2. Awareness of endometrial cancer risk and compliance with screening in hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie

    2012-01-01

    Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...

  3. The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation.

    Science.gov (United States)

    Ayuk, Sandra Matabi; Abrahamse, Heidi; Houreld, Nicolette Nadene

    2016-01-01

    The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

  4. The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation

    Directory of Open Access Journals (Sweden)

    Sandra Matabi Ayuk

    2016-01-01

    Full Text Available The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI or photobiomodulation (PBM is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

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

    African Journals Online (AJOL)

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

  6. Differential in vivo zymography: a method for observing matrix metalloproteinase activity in the zebrafish embryo.

    Science.gov (United States)

    Keow, Jonathan Y; Herrmann, Kurt M; Crawford, Bryan D

    2011-04-01

    Investigations into the molecular mechanisms of, and cellular signaling pathways modulating ECM remodeling are especially challenging due to the complex post-translational regulation of the primary effectors of ECM catabolism - the matrix metalloproteinases (MMPs). Recently a variety of approaches to the detection of MMP activity have been developed, and the prospect of visualizing ECM remodeling activity in living tissues is now opening exciting avenues of research for matrix biologists. In particular the use of FRET-quenched MMP substrates, which generate a fluorescent signal upon hydrolysis, is becoming increasingly popular, especially because linkers with defined and/or restricted proteolytic sensitivity can be used to bind fluorophore-quencher pairs, making these probes useful in characterizing the activity of specific proteases. We have taken advantage of the transparency and amenability to reverse genetics of the zebrafish embryo, in combination with these fluorogenic MMP substrates, to develop a multiplex in vivo assay for MMP activity that we dub "differential in vivo zymography." Copyright © 2011 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  7. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

    Directory of Open Access Journals (Sweden)

    Heleen Rienstra

    Full Text Available BACKGROUND: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. METHODS: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin and chondroitin sulfate proteoglycan (versican expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively expression were (semi- quantitatively analyzed using immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

  8. Long-term and baseline recreational physical activity and risk of endometrial cancer: the California Teachers Study.

    Science.gov (United States)

    Dieli-Conwright, C M; Ma, H; Lacey, J V; Henderson, K D; Neuhausen, S; Horn-Ross, P L; Deapen, D; Sullivan-Halley, J; Bernstein, L

    2013-08-06

    Physical activity may be associated with decreasing endometrial cancer risk; it remains unclear whether the association is modified by body size. Among 93 888 eligible California Teachers Study participants, 976 were diagnosed with incident endometrial cancer between 1995-1996 and 2007. Cox proportional hazards regression methods were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with long-term (high school through age 54 years) and baseline (3 years prior to joining the cohort) strenuous and moderate recreational physical activity, overall and by body size. Increased baseline strenuous recreational physical activity was associated with decreased endometrial cancer risk (Ptrend=0.006) with approximately 25% lower risk among women exercising >3 h per week per year than among those exercising activity was associated with lower risk among overweight/obese women. Increasing physical activity, particularly strenuous activity, may be a lifestyle change that overweight and obese women can implement to reduce their endometrial cancer risk.

  9. Childhood body mass index and height and risk of histologic subtypes of endometrial cancer

    DEFF Research Database (Denmark)

    Aarestrup, J.; Gamborg, M.; Ulrich, L. G.

    2016-01-01

    BACKGROUND: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m(-2)) and height were associated with histologic subtypes of endometrial cancer...

  10. Hysterescopic management of endometrial ossification as a cause of infertility: case report

    Directory of Open Access Journals (Sweden)

    Kubilay Vicdan

    2006-12-01

    Full Text Available Endometrial ossification is a rare pathology, most commonly caused by retention of fetal bones following termination of pregnancy. The most frequent presentation is abnormal vaginal bleeding and discharge, dismenore, pelvic pain and secondary infertility. Here we present a new case of endometrial ossification. A 25 year old woman had attended to a gynecology clinic with a complaint of menorrhagia and vaginal discharge lasting for 3 months. Her medical history revealed a voluntarily termination of pregnancy at 12 weeks of gestation two years ago. The transvaginal ultrasonographic examination showed increased echogenity of the endometrium and calcified mass and the patient underwent D&C. The patient was referred to our clinic with a histopathological diagnosis of mature bony tissue. Hysterescopic evaluation of the patient confirmed the diagnosis and lameller bone fragments were removed. Pathology of the removed material was reported as thick trabekuller bone within endometrial glands. Posthysterescopic transvaginal sonography was normal. After hysterescopic management, the patient decided to use contraceptive pill for one year. She became pregnant spontaneously within 3 months after quiting contraceptive pill. In conclusion, endometrial ossification is a rare, iatrogenic cause of infertility which can be easily diagnosed and managed by histeroscopy.

  11. Evaluation of endometrial carcinoma by multislice dynamic MR imaging with Turbo FLASH

    Energy Technology Data Exchange (ETDEWEB)

    Asakawa, Mari [Okayama Univ. (Japan). School of Medicine

    1995-04-01

    The purpose of this study was to investigate the usefulness of multislice dynamic MR imaging with Turbo FLASH in assessing myometrial invasion by endometrial carcinoma. Dynamic MR imaging was performed with bolus injection of Gd-DTPA and with 1.5-T Siemens Magnetom imager using Turbo FLASH. Thirty-six endometrial carcinomas were evaluated with pathologic correlation. Junctional zone showed more rapid contrast enhancement effects than myometrium even after menopause. Contrast to noise ratio between junctional zone and endometrial carcinoma was the highest about fifty seconds after bolus injection. Only at that time could the degree of invasion to junctional zone in post-menopausal women whose junctional zones could not be seen on T{sub 2}-weighted images or contrast-enhanced T{sub 1}-weighted images be evaluated correctly. The accuracy in assessing myometrial invasion with T{sub 2}-weighted images, postcontrast T{sub 1}-weighted images, and dynamic MR imaging was 75%, 81% and 89% respectively. Though there was no statistically significant difference, multislice dynamic imaging with Turbo FLASH technique is considered to be a useful imaging method for the pre-operative assessment of myometrial invasion by endometrial carcinoma. (author).

  12. Estrogen Metabolism and Risk of Postmenopausal Endometrial and Ovarian Cancer: the B ∼ FIT Cohort.

    Science.gov (United States)

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

    2016-02-01

    Estrogen metabolites may have different genotoxic and mitogenic properties yet their relationship with endometrial and ovarian cancer risk remains unclear. Within the Breast and Bone Follow-up to the Fracture Intervention Trial (B ∼ FIT, n = 15,595), we conducted a case-cohort study to evaluate 15 pre-diagnostic serum estrogens and estrogen metabolites with risk of incident endometrial and ovarian cancer among postmenopausal women not on hormone therapy. Participants included 66 endometrial and 67 ovarian cancer cases diagnosed during follow-up (∼ 10 years) and subcohorts of 346 and 416 women, respectively, after relevant exclusions. Serum concentrations were measured by liquid chromatography-tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. Exposures were categorized in tertiles (T) and analyzed individually, as metabolic pathways (C-2, -4, or -16) and as ratios to parent estrogens (estradiol, estrone). Estradiol was significantly associated with increased endometrial cancer risk (BMI-adjusted HRT3vsT1 = 4.09, 95% CI 1.70, 9.85; p trend = 0.003). 2-Hydroxyestrone and 16α-hydroxyestrone were not associated with endometrial risk after estradiol adjustment (2-OHE1:HRT3vsT1 = 1.97, 95% CI 0.78, 4.94; 16-OHE1:HRT3vsT1 = 1.50, 95% CI 0.65, 3.46; p trend = 0.16 and 0.36, respectively). Ratios of 2- and 4-pathway catechol-to-methylated estrogens remained positively associated with endometrial cancer after BMI or estradiol adjustment (2-pathway catechols-to-methylated: HRT3vsT1 = 4.02, 95% CI 1.60, 10.1; 4-pathway catechols-to-methylated: HRT3vsT1 = 4.59, 95% CI 1.64, 12.9; p trend = 0.002 for both). Estrogens and estrogen metabolites were not associated with ovarian cancer risk; however, larger studies are needed to better evaluate these relationships. Estrogen metabolism may be important in endometrial carcinogenesis, particularly with less extensive methylation of 2- or 4

  13. Isolated splenic metastasis of endometrial adenocarcinoma--a case report.

    Science.gov (United States)

    Andrei, S; Preda, C; Andrei, A; Becheanu, G; Herlea, V; Lupescu, I; Popescu, I

    2011-01-01

    The spleen in rarely the place for solid, non-haematological tumors, isolated splenic metastases from adenocarcinomas being extremely rare findings, regardless of the origin and the histological type of the primary tumor. We present the case of a female patient with isolated splenic metastasis diagnosed by abdominal computer tomography at only 20 months after curative surgery for endometrial adenocarcinoma, in which the final diagnosis has been established by histological and immunohistochemical examination of the splenectomy piece. The haematogenous dissemination of the endometrial cancer occurs most commonly in the lungs, liver or bones, the spleen being rarely affected. In the medical literature there are cited up to date only 12 cases of solitary splenic metastasis from endometrial adenocarcinoma. The particularity of the case presented by us is the early appearance of an isolated splenic metastasis, at less than two years after curative surgery (compared to an average of 4-5 years cited in the literature), from an endometrial cancer which was classified histologicaly in the group with low-risk for relapse (well differentiated endometrioid adenocarcinoma). In conclusion, although solitary splenic secondary determinations are very rare, the incidence of the reported cases in the medical literature is increasing, their late appearance (a few years after the primary tumor's resection) and the lack of symptoms until the tumor reaches appreciable size or it complicates with necrosis, justifies the periodic abdominal imaging examination, on long-term, for postoperative monitorisation after the initial curative surgery. Their treatment of choice is open, classical splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.

  14. Vaginal vault recurrences of endometrial cancer in non-irradiated patients

    DEFF Research Database (Denmark)

    Hardarson, Hordur Alexander; Nyhøj Heidemann, Lene; Christensen, René dePont

    2015-01-01

    are few and limited to previously irradiated patients or patients with advanced disease. Investigation of surgical treatment for isolated vaginal vault recurrence is practically nonexistent. The aim of this study is to evaluate the efficacy of RT and ST in a non-irradiated group with recurrent endometrial...... cancer limited to the vaginal vault. METHODS: Patients treated for recurrent endometrial cancer at Odense University Hospital, Denmark between 2003 and 2012 were identified, n = 118. Thirty-three patients had an isolated vaginal vault recurrence and were treated with either RT, ST or both. Re...

  15. Genetic Variation in the Matrix Metalloproteinase Genes and Diabetic Nephropathy in Type 1 Diabetes

    OpenAIRE

    Kure, Masahiko; Pezzolesi, Marcus G.; Poznik, G. David; Katavetin, Pisut; Skupien, Jan; Dunn, Jonathon S.; Mychaleckyj, Josyf C.; Warram, James H.; Krolewski, Andrzej S.

    2011-01-01

    Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type...

  16. Early increased levels of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome

    NARCIS (Netherlands)

    Dik, Willem A.; van Kaam, Anton H. L. C.; Dekker, Tamara; Naber, Brigitta A. E.; Janssen, Daphne J.; Kroon, A. A.; Zimmermann, Luc J. I.; Versnel, Marjan A.; Lutter, René

    2006-01-01

    Aim: Matrix metalloproteinases (MMPs) play an eminent role in airway injury and remodelling. We explored the hypothesis that pulmonary MMP levels would differ early after birth (2-4 days) between infants with resolving respiratory distress syndrome (RDS) and infants developing chronic lung disease

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

    Directory of Open Access Journals (Sweden)

    Mehri Fayazi

    2016-07-01

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

  18. Transcervical Intrauterine Levobupivacaine or Lidocaine Infusion for Pain Control during Endometrial Biopsy

    Directory of Open Access Journals (Sweden)

    Nermin Kosus

    2014-01-01

    Full Text Available BACKGROUND: Endometrial biopsy is a common procedure for the investigation of many gynecological disorders including abnormal uterine bleeding, postmenopausal bleeding, abnormal cytology and infertility. Most women experience some degree of discomfort and pain during the procedure. Pain may occur during dilation of the cervix for insertion of the catheter and during endometrial biopsy, which further aggravates pain by inducing uterine contraction.

  19. Endometrioid endometrial carcinoma indirectly caused by pituitary prolactinoma: a case report.

    Science.gov (United States)

    Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

    2013-01-01

    We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

  20. Endometrioid Endometrial Carcinoma Indirectly Caused by Pituitary Prolactinoma:A Case Report

    Directory of Open Access Journals (Sweden)

    Kimihiro Nishino

    2013-01-01

    Full Text Available We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

  1. Active matrix metalloproteases are expressed early on and are high during the Barrett's esophagus malignancy sequence

    NARCIS (Netherlands)

    Davelaar, Akueni L.; Straub, Daniëlle; Buttar, Navtej S.; Fockens, Paul; Krishnadath, Kausilia K.

    2015-01-01

    Objective. Molecular processes underlying Barrett's malignant development are poorly understood. Matrix metalloproteases (MMPs) are enzymes involved in inflammation, tissue remodeling, and malignant development. Therefore, active MMPs may have a role in early metaplasia development and Barrett's

  2. Polymorphisms in matrix metalloproteinases MMP1 and MMP9 are associated with primary open-angle and angle closure glaucoma in a Pakistani population

    NARCIS (Netherlands)

    Micheal, S.; Yousaf, S.; Khan, M.I.; Akhtar, F.; Islam, F.; Khan, W.A.; Hollander, A.I. den; Qamar, R.; Ahmed, A.

    2013-01-01

    PURPOSE: Matrix metalloproteinases (MMPs) play an important role in remodeling of the extracellular matrix during development and growth of various tissues including the eye. Various functional polymorphisms in MMPs have been implicated in the pathogenesis of different types of glaucoma. The aim of

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Henrica M J Werner

    Full Text Available Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

  5. Relation of metabolic syndrome with endometrial pathologies in patients with abnormal uterine bleeding.

    Science.gov (United States)

    Özdemir, Suna; Batmaz, Gonca; Ates, Seda; Celik, Cetin; Incesu, Feyzanur; Peru, Celalettin

    2015-01-01

    We aimed to investigate the association of metabolic syndrome and metabolic risk factors with endometrial hyperplasia and carcinoma among women with abnormal uterine bleeding (AUB). This study included 199 patients who had undergone endometrial curettage due to abnormal uterine bleeding. We divided the patients into two groups according to whether they had an abnormal (n = 53) or normal endometrium (n = 146). Waist circumference, blood pressure, fasting glucose and serum lipid levels were measured and statistically analyzed. The women in each group were matched with regard to mean age, gravidity, parity and menopausal status. We found increased prevalence of metabolic syndrome, diabetes, general and abdominal obesity, hypertension, elevated levels of glucose, total cholesterol and LDL-cholesterol and reduced levels of HDL-cholesterol among women with endometrial carcinoma and hyperplasia. These results were detected particularly in postmenopausal (>50 years) women compared to pre-menopausal cases (<50 years). All metabolic parameters were similar between hyperplasia and cancer groups. Metabolic syndrome and its components have been shown to have profound impacts on initiation and progession of endometrial pathology, particularly during post-menopausal period.

  6. Robotic-assisted laparoscopic hysterectomy seems safe in women with early-stage endometrial cancer

    DEFF Research Database (Denmark)

    Herling, Suzanne Forsyth; Havemann, Maria Cecilie; Palle, Connie

    2015-01-01

    INTRODUCTION: Robotic surgery is increasingly used in the management of endometrial cancer; and although it is known that minimally invasive surgery reduces post-operative morbidity, the outcomes of this novel treatment should be monitored carefully. The aim of this study was to examine the incid......INTRODUCTION: Robotic surgery is increasingly used in the management of endometrial cancer; and although it is known that minimally invasive surgery reduces post-operative morbidity, the outcomes of this novel treatment should be monitored carefully. The aim of this study was to examine...... the incidence of complications according to the Clavien-Dindo scale after robotic-assisted laparoscopic hysterectomy (RALH) for early-stage endometrial cancer and atypical complex hyperplasia. The Clavien-Dindo scale grades the severity of complications. METHODS: This was a retrospective, descriptive cohort....... CONCLUSION: The types and frequency of complications observed in this study resemble those reported in similar studies of RALH for malignant gynaecologic conditions. Health-care professionals treating and caring for women with early-stage endometrial cancer should know of the types and frequency of post...

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

    NARCIS (Netherlands)

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

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

  8. The Latest Twists in Chromatin Remodeling.

    Science.gov (United States)

    Blossey, Ralf; Schiessel, Helmut

    2018-01-05

    In its most restrictive interpretation, the notion of chromatin remodeling refers to the action of chromatin-remodeling enzymes on nucleosomes with the aim of displacing and removing them from the chromatin fiber (the effective polymer formed by a DNA molecule and proteins). This local modification of the fiber structure can have consequences for the initiation and repression of the transcription process, and when the remodeling process spreads along the fiber, it also results in long-range effects essential for fiber condensation. There are three regulatory levels of relevance that can be distinguished for this process: the intrinsic sequence preference of the histone octamer, which rules the positioning of the nucleosome along the DNA, notably in relation to the genetic information coded in DNA; the recognition or selection of nucleosomal substrates by remodeling complexes; and, finally, the motor action on the nucleosome exerted by the chromatin remodeler. Recent work has been able to provide crucial insights at each of these three levels that add new twists to this exciting and unfinished story, which we highlight in this perspective. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Time trends in the incidence of hysterectomy-corrected overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014.

    Science.gov (United States)

    Faber, Mette Tuxen; Frederiksen, Kirsten; Jensen, Allan; Aarslev, Peter Bo; Kjaer, Susanne K

    2017-08-01

    To investigate time trends in the incidence of overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014, correcting for hysterectomy. Based on the Danish Cancer Registry and the Danish National Patient Registry we calculated hysterectomy-corrected incidence rates of overall, type 1 and type 2 endometrial cancer. Separate analyses for women incidence with 95% confidence intervals (CI). The overall incidence of endometrial cancer decreased slightly from 1978 to 1995, but in the last two decades of the study period the incidence has been stable (APC=0.16; 95% CI: -0.19; 0.50). In the study period (1978-2014) type 1 endometrial cancer incidence decreased slightly (APC=-0.67; 95% CI:-0.83; -0.52), whereas the incidence of type 2 endometrial cancer increased substantially (APC=4.85; 95% CI: 4.47; 5.23). The decrease in type 1 endometrial cancer was most pronounced before 1996 in women younger than 55 years (APC=-2.79; 95% CI: -3.65; -1.91), while the largest increase in type 2 endometrial cancer was observed after 1996 (APC=6.42; 95% CI: 5.72; 7.12). Over a period of more than 35 years, the incidence of type 1 endometrial cancer decreased, mainly in pre- and perimenopausal women, while type 2 endometrial cancer incidence increased. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Yali Cheng

    2017-12-01

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

  11. Analysis of acute and late toxicity of adjuvant radiotherapy in women with cervical and endometrial cancer

    International Nuclear Information System (INIS)

    Warenczak-Florczak, Z.; Roszak, A.; Wlodarczyk, H.; Wojciechowska-Lacka, A.

    2011-01-01

    Background: In case of pure prognostic factors women with cervical and endometrial cancer after surgical operation need to be treated with radiotherapy . Every radiation treatment may be involved with toxicity, acute and late. Material and methods: Performed was detailed analysis of 173 patients with cervical (38) and endometrial (135) cancer. We evaluated early and late post radiation reactions in all patients. Results: Acute reactions were found in 48.5% and late toxicity was found in 9.8% of patients. Women with endometrial cancer were significantly older then patients with cervical cancer (p < 0.002). Higher percentage of acute and late toxicity was observed from the bowel tah urinary tract (26% and 22.5% - acute; 8.1% and 1.73% - late). Higher percentage of acute side effects was observed in patients with cervical than with endometrial cancer (60.5% and 33.7%). Late post radiation reaction predominate also in patient with cervical cancer (13.2% and 8.9%). The adverse effects were associated with prolonged time of treatment due to breaks in radiotherapy. Higher percentage of breaks was found in older patients, more frequent in patient with endometrial than in cervical cancer group (7.4% and 2.6%).To conclude early postradiation reaction appeared more frequently, than late post radiation reactions. It was stated that early and late post radiation reaction appear more frequently in women with cervical than in endometrial cancer. Interruption in radiation delivery was longer than seven days in group with endometrial cancer that leads to extension of complete radiation treatment. (authors)

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

    Directory of Open Access Journals (Sweden)

    Zhao Jing

    2012-11-01

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

  13. Validity of pipelle endometrial sampling in the patients with abnormaluterine bleeding

    International Nuclear Information System (INIS)

    Fakhar, S.; Saeed, G.; Khan, A.H.; Alam, A.Y.

    2008-01-01

    We compared endometrial sampling by pipelle endometrial curette withconventional dilatation and curettage (D and C) in patients with abnormaluterine bleeding. Endometrial sampling with pipelle curette was performed on100 patients followed by formal D and C. Samples were labeled as A and B,respectively, and sent to a histopathologist who was blinded as to the methodof sampling. The histopathology reports of both samples were compared, takingD and C as the gold standard. An adequate sample was obtained in 98% of casesby pipelle and in 100% of cases by D and C. Pipelle had sensitivity,specificity, positive predictive value of 100% for diagnosing endometrialcarcinoma, hyperplasia and secretory endometrium. Pipelle also had highdiagnostic sensitivity, specificity and negative predictive value (100%, 98%and 100%, respectively) for hyperplasia with atypia and low sensitivity (57%)and positive predictive value (57%), but high specificity (97%) and negativepredictive value (97%) for endometritis. Similarly, for proliferativeendometrium, the pipelle technique had values of 94% and 93% for sensitivityand specificity, respectively. Both samples labeled as inadequate forhistology by pipelle were polyps on the D and C report. Difficultendotracheal intubation was encountered in two cases of D and C. No othercomplications of the procedure were observed. The pipelle is a safe devicefor getting an adequate endometrial sample for histology, with a highsensitivity and specificity for detection of hyperplasia and malignancy.(author)

  14. Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

    Science.gov (United States)

    Crane, Janet L.; Cao, Xu

    2013-01-01

    Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

  15. Function of matrix IGF-1 in coupling bone resorption and formation.

    Science.gov (United States)

    Crane, Janet L; Cao, Xu

    2014-02-01

    Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

  16. Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis.

    Science.gov (United States)

    Rossi, Peter J; Jani, Ashesh B; Horowitz, Ira R; Johnstone, Peter A S

    2008-01-01

    To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p primary tumor was present, the addition of BT to EBRT was even more beneficial.

  17. Correlation between three-dimensional power Doppler and morphometric measurement of endometrial vascularity at the time of embryo implantation in women with unexplained recurrent miscarriage.

    Science.gov (United States)

    Chen, Xiaoyan; Saravelos, Sotirios H; Liu, Yingyu; Huang, Jin; Wang, Chi Chiu; Li, Tin Chiu

    2017-06-01

    Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH + 7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.

  18. Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

    Science.gov (United States)

    Silpanisong, Jinjutha; Pearce, William J.

    2015-01-01

    Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling. Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor (HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation. PMID:24063376

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

    Science.gov (United States)

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

    2017-06-01

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

  20. Atrial remodelling in atrial fibrillation: CaMKII as a nodal proarrhythmic signal

    Science.gov (United States)

    Mesubi, Olurotimi O.; Anderson, Mark E.

    2016-01-01

    CaMKII is a serine–threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflammation, and metabolism. Furthermore, CaMKII inhibition appears to protect against AF in animal models and correct proarrhythmic, defective intracellular Ca2+ homeostasis in fibrillating human atrial cells. This review considers current concepts and evidence from animal and human studies on the role of CaMKII in AF. PMID:26762270