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Sample records for junction squamous epithelial

  1. Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins.

    Science.gov (United States)

    Chen, Xin; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Matsumoto, Takayuki; Miwa, Hiroto

    2011-08-01

    Experimental models for esophageal epithelium in vitro either suffer from poor differentiation or complicated culture systems. An air-liquid interface system with normal human bronchial epithelial cells can serve as a model of esophageal-like squamous epithelial cell layers. Here, we explore the influence of bile acids on barrier function and tight junction (TJ) proteins. The cells were treated with taurocholic acid (TCA), glycocholic acid (GCA), or deoxycholic acid (DCA) at different pH values, or with pepsin. Barrier function was measured by transepithelial electrical resistance (TEER) and the diffusion of paracellular tracers (permeability). The expression of TJ proteins, including claudin-1 and claudin-4, was examined by Western blotting of 1% Nonidet P-40-soluble and -insoluble fractions. TCA and GCA dose-dependently decreased TEER and increased paracellular permeability at pH 3 after 1 h. TCA (4 mM) or GCA (4 mM) did not change TEER and permeability at pH 7.4 or pH 4. The combination of TCA and GCA at pH 3 significantly decreased TEER and increased permeability at lower concentrations (2 mM). Pepsin (4 mg/ml, pH 3) did not have any effect on barrier function. DCA significantly decreased the TEER and increased permeability at pH 6, a weakly acidic condition. TCA (4 mM) and GCA (4 mM) significantly decreased the insoluble fractions of claudin-1 and claudin-4 at pH 3. In conclusion, acidic bile salts disrupted the squamous epithelial barrier function partly by modulating the amounts of claudin-1 and claudin-4. These results provide new insights for understanding the role of TJ proteins in esophagitis.

  2. In vitro adherence patterns of Shigella serogroups to bovine recto-anal junction squamous epithelial (RSE) cells are similar to those of Escherichia coli O157

    Science.gov (United States)

    The aim of this study was to determine whether Shigella species, which are human gastrointestinal pathogens, can adhere to cattle recto-anal junction squamous epithelial (RSE) cells using a recently standardized adherence assay, and to compare their adherence patterns to that of Escherichia coli O15...

  3. Bovine recto-anal junction squamous epithelial (RSE) cell adhesion assay for studying Escherichia coli O157 adherence.

    Science.gov (United States)

    Kudva, I T; Dean-Nystrom, E A

    2011-11-01

    To develop a new adherence assay, using cattle recto-anal junction squamous epithelial (RSE) cells, for evaluating bacterial adherence to cells of bovine origin. Proof of concept was demonstrated using the human gastrointestinal pathogen Escherichia coli O157:H7, for which cattle are reservoirs. Adherence assays were conducted using both RSE and HEp-2 cells, in the presence and absence of D+Mannose. E. coli O157 specifically adhered in a type I fimbriae-independent manner to RSE cells in significantly higher numbers and also bound significantly higher numbers of RSE cells than diverse laboratory strains of nonpathogenic E. coli. The RSE cell adhesion assay output highly reproducible and interpretable results that compared very well with those obtained using the more extensively used HEp-2 cell adherence assay. The RSE cell adhesion assay provides a convenient means of directly defining and evaluating pathogen factors operating at the bovine recto-anal junction. The RSE cell adhesion assay further has the potential for extrapolation to diverse bacteria, including food-borne pathogens that colonize cattle via adherence to this particular anatomical site. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

  4. In vitro adherence patterns of Shigella serogroups to bovine recto-anal junction squamous epithelial (RSE) cells are similar to those of Escherichia coli O157.

    Science.gov (United States)

    Kudva, Indira T

    2012-04-01

    The aims of this study were to determine whether Shigella species, which are human gastrointestinal pathogens, can adhere to cattle recto-anal junction squamous epithelial (RSE) cells using a recently standardized in vitro adherence assay, and to compare their adherence patterns with that of Escherichia coli O157. Shigella dysenteriae (serogroup A), S. flexneri (serogroup B), S. boydii (serogroup C), and S. sonnei (serogroup D) were tested in adherence assays using both RSE and HEp-2 cells, in the presence or absence of D+mannose. Escherichia coli O157, which adheres to RSE cells in a Type I fimbriae-independent manner, was used as a positive control. Shigella serogroups A, B, D, but not C adhered to RSE cells with distinct adherence patterns in the presence of D+mannose. No such distinction could be made between the four Shigella serogroups based on the HEp-2 cell adherence patterns. Thus, this study provides evidence that certain Shigella serogroups adhere to RSE cells in a manner that is similar to the adherence pattern of E. coli O157. These unexpected observations of in vitro binding of these foodborne human pathogens to cells of the bovine gastrointestinal tract warrant evaluation of Shigella carriage by cattle using both experimental and observational studies, especially for serogroups B and D. Such studies are currently underway.

  5. Curli Temper Adherence of Escherichia coli O157:H7 to Squamous Epithelial Cells from the Bovine Recto-Anal Junction in a Strain-Dependent Manner.

    Science.gov (United States)

    Kudva, Indira T; Carter, Michelle Q; Sharma, Vijay K; Stasko, Judith A; Giron, Jorge A

    2017-01-01

    Our recent studies have shown that intimin and the locus of enterocyte effacement-encoded proteins do not play a role in Escherichia coli O157:H7 (O157) adherence to the bovine recto-anal junction squamous epithelial (RSE) cells. To define factors that play a contributory role, we investigated the role of curli, fimbrial adhesins commonly implicated in adherence to various fomites and plant and human epithelial cells, in O157 adherence to RSE cells. Specifically, we examined (i) wild-type strains of O157; (ii) curli variants of O157 strains; (iii) isogenic curli deletion mutants of O157; and (iv) adherence inhibition of O157 using anti-curlin sera. Results of these experiments conducted under stringent conditions suggest that curli do not solely contribute to O157 adherence to RSE cells and in fact demonstrate a modulating effect on O157 adherence to RSE cells in contrast to HEp-2 cells (human epidermoid carcinoma of the larynx cells with HeLa contamination). The absence of curli and presence of blocking anti-curli antibodies enhanced O157-RSE cell interactions among some strains, thus alluding to a spatial, tempering effect of curli on O157 adherence to RSE cells when present. At the same time, the presence or absence of curli did not alter RSE cell adherence patterns of another O157 strain. These observations are at variance with the reported role of curli in O157 adherence to human cell lines such as HEp-2 and need to be factored in when developing anti-adherence modalities for preharvest control of O157 in cattle.

  6. The Escherichia coli O157:H7 cattle immunoproteome includes outer membrane protein A (OmpA), a modulator of adherence to bovine rectoanal junction squamous epithelial (RSE) cells.

    Science.gov (United States)

    Kudva, Indira T; Krastins, Bryan; Torres, Alfredo G; Griffin, Robert W; Sheng, Haiqing; Sarracino, David A; Hovde, Carolyn J; Calderwood, Stephen B; John, Manohar

    2015-06-01

    Building on previous studies, we defined the repertoire of proteins comprising the immunoproteome (IP) of Escherichia coli O157:H7 (O157) cultured in DMEM supplemented with norepinephrine (O157 IP), a β-adrenergic hormone that regulates E. coli O157 gene expression in the gastrointestinal tract, using a variation of a novel proteomics-based platform proteome mining tool for antigen discovery, called "proteomics-based expression library screening" (PELS; Kudva et al., 2006). The E. coli O157 IP (O157-IP) comprised 91 proteins, and included those identified previously using proteomics-based expression library screening, and also proteins comprising DMEM and bovine rumen fluid proteomes. Outer membrane protein A (OmpA), a common component of the above proteomes, and reportedly a contributor to E. coli O157 adherence to cultured HEp-2 epithelial cells, was interestingly found to be a modulator rather than a contributor to E. coli O157 adherence to bovine rectoanal junction squamous epithelial cells. Our results point to a role for yet to be identified members of the O157-IP in E. coli O157 adherence to rectoanal junction squamous epithelial cells, and additionally implicate a possible role for the outer membrane protein A regulator, TdcA, in the expression of such adhesins. Our observations have implications for the development of efficacious vaccines for preventing E. coli O157 colonization of the bovine gastrointestinal tract.

  7. The Escherichia coli O157:H7 cattle immuno-proteome includes outer membrane protein A (OmpA), a modulator of adherence to bovine recto-anal junction squamous epithelial (RSE) cells

    Science.gov (United States)

    Kudva, Indira T.; Krastins, Bryan; Torres, Alfredo G.; Griffin, Robert W.; Sheng, Haiqing; Sarracino, David A.; Hovde, Carolyn J.; Calderwood, Stephen B.; John, Manohar

    2015-01-01

    SUMMARY Building on previous studies, we defined the repertoire of proteins comprising the immuno-proteome of E. coli O157:H7 (O157) cultured in DMEM supplemented with norepinephrine (NE; O157 immuno-proteome), a β-adrenergic hormone that regulates E. coli O157 gene expression in the gastrointestinal tract, using a variation of a novel proteomics-based platform proteome mining tool for antigen discovery, called Proteomics-based Expression Library Screening (PELS; Kudva et al., 2006). The E. coli O157 immuno-proteome (O157-IP) comprised 91 proteins, and included those identified previously using PELS, and also proteins comprising DMEM- and bovine rumen fluid- proteomes. Outer membrane protein A (OmpA), a common component of the above proteomes, and reportedly a contributor to E. coli O157 adherence to cultured Hep-2 epithelial cells, was interestingly found to be a modulator rather than a contributor to E. coli O157 adherence to bovine recto-anal junction squamous epithelial (RSE) cells. Our results point to a role for yet to be identified members of the O157-IP in E. coli O157 adherence to RSE-cells, and additionally implicate a possible role for the OmpA regulator, TdcA, in the expression of such adhesins. Our observations have implications for development of efficacious vaccines for preventing E. coli O157 colonization of the bovine gastrointestinal tract. PMID:25643951

  8. Comparative analysis of super-shedder strains of Escherichia coli O157:H7 reveals distinctive genomic features and a strongly aggregative adherent phenotype on bovine rectoanal junction squamous epithelial cells.

    Directory of Open Access Journals (Sweden)

    Rebecca Cote

    Full Text Available Shiga toxin-producing Escherichia coli O157:H7 (O157 are significant foodborne pathogens and pose a serious threat to public health worldwide. The major reservoirs of O157 are asymptomatic cattle which harbor the organism in the terminal recto-anal junction (RAJ. Some colonized animals, referred to as "super-shedders" (SS, are known to shed O157 in exceptionally large numbers (>104 CFU/g of feces. Recent studies suggest that SS cattle play a major role in the prevalence and transmission of O157, but little is known about the molecular mechanisms associated with super-shedding. Whole genome sequence analysis of an SS O157 strain (SS17 revealed a genome of 5,523,849 bp chromosome with 5,430 open reading frames and two plasmids, pO157 and pSS17, of 94,645 bp and 37,446 bp, respectively. Comparative analyses showed that SS17 is clustered with spinach-associated O157 outbreak strains, and belongs to the lineage I/II, clade 8, D group, and genotype 1, a subgroup of O157 with predicted hyper-virulence. A large number of non-synonymous SNPs and other polymorphisms were identified in SS17 as compared with other O157 strains (EC4115, EDL933, Sakai, TW14359, including in key adherence- and virulence-related loci. Phenotypic analyses revealed a distinctive and strongly adherent aggregative phenotype of SS17 on bovine RAJ stratified squamous epithelial (RSE cells that was conserved amongst other SS isolates. Molecular genetic and functional analyses of defined mutants of SS17 suggested that the strongly adherent aggregative phenotype amongst SS isolates is LEE-independent, and likely results from a novel mechanism. Taken together, our study provides a rational framework for investigating the molecular mechanisms associated with SS, and strong evidence that SS O157 isolates have distinctive features and use a LEE-independent mechanism for hyper-adherence to bovine rectal epithelial cells.

  9. Transcriptional mechanisms coordinating tight junction assembly during epithelial differentiation.

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    Boivin, Felix J; Schmidt-Ott, Kai M

    2017-06-01

    Epithelial tissues form a selective barrier via direct cell-cell interactions to separate and establish concentration gradients between the different compartments of the body. Proper function and formation of this barrier rely on the establishment of distinct intercellular junction complexes. These complexes include tight junctions, adherens junctions, desmosomes, and gap junctions. The tight junction is by far the most diverse junctional complex in the epithelial barrier. Its composition varies greatly across different epithelial tissues to confer various barrier properties. Thus, epithelial cells rely on tightly regulated transcriptional mechanisms to ensure proper formation of the epithelial barrier and to achieve tight junction diversity. Here, we review different transcriptional mechanisms utilized during embryogenesis and disease development to promote tight junction assembly and maintenance of intercellular barrier integrity. We focus particularly on the Grainyhead-like transcription factors and ligand-activated nuclear hormone receptors, two central families of proteins in epithelialization. © 2017 New York Academy of Sciences.

  10. No junctional communication between epithelial cells in hydra

    DEFF Research Database (Denmark)

    de Laat, S W; Tertoolen, L G; Grimmelikhuijzen, C J

    1980-01-01

    junctions between epithelial cells of hydra. However, until now, there has been no report published on whether these junctions enable the epithelial cells to exchange molecules of small molecular weight, as has been described in other organisms. Therefore we decided to investigate the communicative...... properties of the junctional membranes by electrophysiological methods and by intracellular-dye iontophoresis. We report here that no electrotonic coupling is detectable between epithelial cells of Hydra attenuata in: (1) intact animals, (2) head-regenerating animals, (3) cell re-aggregates, and (4) hydra...

  11. Trichomonas vaginalis perturbs the junctional complex in epithelial cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Trichomonas vaginalis, a protist parasite of the urogenital tract in humans, is the causative agent of trichomonosis,which in recent years have been associated with the cervical cancer development. In the present study we analyzed the modifications at the junctional complex level of Caco-2 cells after interaction with two isolates of T. vaginalis and the influence of the iron concentration present in the parasite's culture medium on the interaction effects. Our results show that T. vaginalis adheres to the epithelial cell causing alterations in the junctional complex, such as: (a) a decrease in transepithelial electrical resistance; (b) alteration in the pattern of junctional complex proteins distribution as obseryed for E-cadherin, occludin and ZO-1; and (c) enlargement of the spaces between epithelial cells. These effects were dependent on (a) the degree of the parasite virulence isolate, (b) the iron concentration in the culture medium, and (c) the expression of adhesin proteins on the parasite surface.

  12. Defining functional interactions during biogenesis of epithelial junctions

    Science.gov (United States)

    Erasmus, J. C.; Bruche, S.; Pizarro, L.; Maimari, N.; Pogglioli, T.; Tomlinson, C.; Lees, J.; Zalivina, I.; Wheeler, A.; Alberts, A.; Russo, A.; Braga, V. M. M.

    2016-01-01

    In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. PMID:27922008

  13. Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.

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    Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

    2015-04-01

    The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.

  14. Altered expression of epithelial junctional proteins in atopic asthma: Possible role in inflammation

    NARCIS (Netherlands)

    W.I. de Boer (Pim); H.S. Sharma (Hari); S.M. Baelemans (Sophia); H.C. Hoogsteden (Henk); B.N.M. Lambrecht (Bart); G.J. Braunstahl (Gert-Jan)

    2008-01-01

    textabstractEpithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the

  15. Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions.

    Science.gov (United States)

    Lechuga, Susana; Baranwal, Somesh; Ivanov, Andrei I

    2015-05-01

    Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis.

  16. Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas

    DEFF Research Database (Denmark)

    Nielsen, P A; Mandel, U; Therkildsen, M H

    1997-01-01

    Stratified squamous epithelia of oral and cervical mucosa express high levels of simple mucin-type O-linked carbohydrates, and these are known to undergo structural changes in relation to epithelial differentiation and neoplastic transformation. O-glycans in these epithelia are associated with th...

  17. Neisseria gonorrhoeae breaches the apical junction of polarized epithelial cells for transmigration by activating EGFR.

    Science.gov (United States)

    Edwards, Vonetta L; Wang, Liang-Chun; Dawson, Valerie; Stein, Daniel C; Song, Wenxia

    2013-06-01

    Neisseria gonorrhoeae initiates infection at the apical surface of columnar endocervical epithelial cells in the female reproductive tract. These cells provide a physical barrier against pathogens by forming continuous apical junctional complexes between neighbouring cells. This study examines the interaction of gonococci (GC) with polarized epithelial cells. We show that viable GC preferentially localize at the apical side of the cell-cell junction in polarized endometrial and colonic epithelial cells, HEC-1-B and T84. In GC-infected cells, continuous apical junctional complexes are disrupted, and the junction-associated protein β-catenin is redistributed from the apical junction to the cytoplasm and to GC adherent sites; however, overall cellular levels remain unchanged. This redistribution of junctional proteins is associated with a decrease in the 'fence' function of the apical junction but not its 'gate' function. Disruption of the apical junction by removing calcium increases GC transmigration across the epithelial monolayer. GC inoculation induces the phosphorylation of both epidermal growth factor receptor (EGFR) and β-catenin, while inhibition of EGFR kinase activity significantly reduces both GC-induced β-catenin redistribution and GC transmigration. Therefore, the gonococcus is capable of weakening the apical junction and polarity of epithelial cells by activating EGFR, which facilitates GC transmigration across the epithelium.

  18. A membrane fusion protein αSNAP is a novel regulator of epithelial apical junctions.

    Directory of Open Access Journals (Sweden)

    Nayden G Naydenov

    Full Text Available Tight junctions (TJs and adherens junctions (AJs are key determinants of the structure and permeability of epithelial barriers. Although exocytic delivery to the cell surface is crucial for junctional assembly, little is known about the mechanisms controlling TJ and AJ exocytosis. This study was aimed at investigating whether a key mediator of exocytosis, soluble N-ethylmaleimide sensitive factor (NSF attachment protein alpha (αSNAP, regulates epithelial junctions. αSNAP was enriched at apical junctions in SK-CO15 and T84 colonic epithelial cells and in normal human intestinal mucosa. siRNA-mediated knockdown of αSNAP inhibited AJ/TJ assembly and establishment of the paracellular barrier in SK-CO15 cells, which was accompanied by a significant down-regulation of p120-catenin and E-cadherin expression. A selective depletion of p120 catenin effectively disrupted AJ and TJ structure and compromised the epithelial barrier. However, overexpression of p120 catenin did not rescue the defects of junctional structure and permeability caused by αSNAP knockdown thereby suggesting the involvement of additional mechanisms. Such mechanisms did not depend on NSF functions or induction of cell death, but were associated with disruption of the Golgi complex and down-regulation of a Golgi-associated guanidine nucleotide exchange factor, GBF1. These findings suggest novel roles for αSNAP in promoting the formation of epithelial AJs and TJs by controlling Golgi-dependent expression and trafficking of junctional proteins.

  19. Intestinal epithelial barrier function and tight junction proteins with heat and exercise

    DEFF Research Database (Denmark)

    Dokladny, Karol; Zuhl, Micah N; Moseley, Pope L

    2016-01-01

    (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional...... interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise....

  20. A chemically defined culture medium containing Rho kinase inhibitor Y-27632 for the fabrication of stratified squamous epithelial cell grafts.

    Science.gov (United States)

    Aslanova, Afag; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Yamamoto, Masakazu

    2015-05-01

    With the development of a culture method for stratified squamous epithelial cells, tissue-engineered epithelial cell sheets have been successfully applied as clinical cell grafts. However, the implementation of these cell sheets without the use of any animal-derived materials is highly desirable. In this study, Rho-associated protein kinase inhibitor Y-27632 was used to develop a chemically defined culture medium for the fabrication of stratified epithelial cell grafts consisting of human epidermal and oral keratinocytes, and the proliferation activity, cell morphology, and gene expressions of the keratinocytes were analyzed. The results of a colorimetric assay indicated that Y-27632 significantly promoted the proliferation of the keratinocytes in culture media both with and without fetal bovine serum (FBS), although there were no indications of Y-27632 efficacy on cell morphology and stratification of the keratinocytes in culture medium without any animal-derived materials. The results of quantitative RT-PCR revealed that gene expressions correlated with cell adhesion, cell-cell junction, proliferation markers, and stem/progenitor markers in cultured keratinocytes were not strongly affected by the addition of Y-27632 to the culture medium. Moreover, gene expressions of differentiation markers in stratified keratinocytes cultured in medium without FBS were nearly identical to those of keratinocytes co-cultured with 3T3 feeder cells. Interestingly, the expressions of differentiation markers in cultured stratified keratinocytes were suppressed by FBS, whereas they were reconstructed by either co-culture of a 3T3 feeder layer or addition of Y-27632 into the culture medium containing FBS. These findings indicate that Y-27632 is a useful supplement for the development of a chemically defined culture medium for fabrication of stratified epithelial cell grafts for clinical applications for the purpose of developing the culture medium with a lower risk of pathogen

  1. The Rho Target PRK2 Regulates Apical Junction Formation in Human Bronchial Epithelial Cells ▿

    OpenAIRE

    Wallace, Sean W.; Magalhaes, Ana; Hall, Alan

    2010-01-01

    Rho GTPases regulate multiple signaling pathways to control a number of cellular processes during epithelial morphogenesis. To investigate the downstream pathways through which Rho regulates epithelial apical junction formation, we screened a small interfering RNA (siRNA) library targeting 28 known Rho target proteins in 16HBE human bronchial epithelial cells. This led to the identification of the serine-threonine kinase PRK2 (protein kinase C-related kinase 2, also called PKN2). Depletion of...

  2. Reversible Opening of Intercellular Junctions of Intestinal Epithelial and Brain Endothelial Cells With Tight Junction Modulator Peptides.

    Science.gov (United States)

    Bocsik, Alexandra; Walter, Fruzsina R; Gyebrovszki, Andrea; Fülöp, Lívia; Blasig, Ingolf; Dabrowski, Sebastian; Ötvös, Ferenc; Tóth, András; Rákhely, Gábor; Veszelka, Szilvia; Vastag, Monika; Szabó-Révész, Piroska; Deli, Mária A

    2016-02-01

    The intercellular junctions restrict the free passage of hydrophilic compounds through the paracellular clefts. Reversible opening of the tight junctions of biological barriers is investigated as one of the ways to increase drug delivery to the systemic circulation or the central nervous system. Six peptides, ADT-6, HAV-6, C-CPE, 7-mer (FDFWITP, PN-78), AT-1002, and PN-159, acting on different integral membrane and linker junctional proteins were tested on Caco-2 intestinal epithelial cell line and a coculture model of the blood-brain barrier. All peptides tested in nontoxic concentrations showed a reversible tight junctions modulating effect and were effective to open the paracellular pathway for the marker molecules fluorescein and albumin. The change in the structure of cell-cell junctions was verified by immunostaining for occludin, claudin-4,-5, ZO-1, β-catenin, and E-cadherin. Expression levels of occludin and claudins were measured in both models. We could demonstrate a selectivity of C-CPE, ADT-6, and HAV-6 peptides for epithelial cells and 7-mer and AT-1002 peptides for brain endothelial cells. PN-159 was the most effective modulator of junctional permeability in both models possibly acting via claudin-1 and -5. Our results indicate that these peptides can be effectively and selectively used as potential pharmaceutical excipients to improve drug delivery across biological barriers.

  3. The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells.

    Science.gov (United States)

    Wallace, Sean W; Magalhaes, Ana; Hall, Alan

    2011-01-01

    Rho GTPases regulate multiple signaling pathways to control a number of cellular processes during epithelial morphogenesis. To investigate the downstream pathways through which Rho regulates epithelial apical junction formation, we screened a small interfering RNA (siRNA) library targeting 28 known Rho target proteins in 16HBE human bronchial epithelial cells. This led to the identification of the serine-threonine kinase PRK2 (protein kinase C-related kinase 2, also called PKN2). Depletion of PRK2 does not block the initial formation of primordial junctions at nascent cell-cell contacts but does prevent their maturation into apical junctions. PRK2 is recruited to primordial junctions, and this localization depends on its C2-like domain. Rho binding is essential for PRK2 function and also facilitates PRK2 recruitment to junctions. Kinase-dead PRK2 acts as a dominant-negative mutant and prevents apical junction formation. We conclude that PRK2 is recruited to nascent cell-cell contacts through its C2-like and Rho-binding domains and promotes junctional maturation through a kinase-dependent pathway.

  4. Epithelial cell-cell junctions and plasma membrane domains

    NARCIS (Netherlands)

    Giepmans, Ben N. G.; van Ijzendoorn, Sven C. D.

    Epithelial cells form a barrier against the environment, but are also required for the regulated exchange of molecules between an organism and its surroundings. Epithelial cells are characterised by a remarkable polarization of their plasma membrane, evidenced by the appearance of structurally,

  5. Epithelial cell-cell junctions and plasma membrane domains

    NARCIS (Netherlands)

    Giepmans, Ben N. G.; van Ijzendoorn, Sven C. D.

    2009-01-01

    Epithelial cells form a barrier against the environment, but are also required for the regulated exchange of molecules between an organism and its surroundings. Epithelial cells are characterised by a remarkable polarization of their plasma membrane, evidenced by the appearance of structurally, comp

  6. A chemically defined culture medium containing Rho kinase inhibitor Y-27632 for the fabrication of stratified squamous epithelial cell grafts

    Energy Technology Data Exchange (ETDEWEB)

    Aslanova, Afag [Department of Surgery, Institute of Gastroenterology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Institute of Advanced Biomedical Engineering and Science, Tokyo Women' s Medical University, TWIns, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Takagi, Ryo; Yamato, Masayuki; Okano, Teruo [Institute of Advanced Biomedical Engineering and Science, Tokyo Women' s Medical University, TWIns, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan); Yamamoto, Masakazu, E-mail: yamamoto.ige@twmu.ac.jp [Department of Surgery, Institute of Gastroenterology, Tokyo Women' s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666 (Japan)

    2015-05-01

    With the development of a culture method for stratified squamous epithelial cells, tissue-engineered epithelial cell sheets have been successfully applied as clinical cell grafts. However, the implementation of these cell sheets without the use of any animal-derived materials is highly desirable. In this study, Rho-associated protein kinase inhibitor Y-27632 was used to develop a chemically defined culture medium for the fabrication of stratified epithelial cell grafts consisting of human epidermal and oral keratinocytes, and the proliferation activity, cell morphology, and gene expressions of the keratinocytes were analyzed. The results of a colorimetric assay indicated that Y-27632 significantly promoted the proliferation of the keratinocytes in culture media both with and without fetal bovine serum (FBS), although there were no indications of Y-27632 efficacy on cell morphology and stratification of the keratinocytes in culture medium without any animal-derived materials. The results of quantitative RT-PCR revealed that gene expressions correlated with cell adhesion, cell–cell junction, proliferation markers, and stem/progenitor markers in cultured keratinocytes were not strongly affected by the addition of Y-27632 to the culture medium. Moreover, gene expressions of differentiation markers in stratified keratinocytes cultured in medium without FBS were nearly identical to those of keratinocytes co-cultured with 3T3 feeder cells. Interestingly, the expressions of differentiation markers in cultured stratified keratinocytes were suppressed by FBS, whereas they were reconstructed by either co-culture of a 3T3 feeder layer or addition of Y-27632 into the culture medium containing FBS. These findings indicate that Y-27632 is a useful supplement for the development of a chemically defined culture medium for fabrication of stratified epithelial cell grafts for clinical applications for the purpose of developing the culture medium with a lower risk of pathogen

  7. Proteomic and bioinformatic analysis of epithelial tight junction reveals an unexpected cluster of synaptic molecules

    Directory of Open Access Journals (Sweden)

    Tang Vivian W

    2006-12-01

    Full Text Available Abstract Background Zonula occludens, also known as the tight junction, is a specialized cell-cell interaction characterized by membrane "kisses" between epithelial cells. A cytoplasmic plaque of ~100 nm corresponding to a meshwork of densely packed proteins underlies the tight junction membrane domain. Due to its enormous size and difficulties in obtaining a biochemically pure fraction, the molecular composition of the tight junction remains largely unknown. Results A novel biochemical purification protocol has been developed to isolate tight junction protein complexes from cultured human epithelial cells. After identification of proteins by mass spectroscopy and fingerprint analysis, candidate proteins are scored and assessed individually. A simple algorithm has been devised to incorporate transmembrane domains and protein modification sites for scoring membrane proteins. Using this new scoring system, a total of 912 proteins have been identified. These 912 hits are analyzed using a bioinformatics approach to bin the hits in 4 categories: configuration, molecular function, cellular function, and specialized process. Prominent clusters of proteins related to the cytoskeleton, cell adhesion, and vesicular traffic have been identified. Weaker clusters of proteins associated with cell growth, cell migration, translation, and transcription are also found. However, the strongest clusters belong to synaptic proteins and signaling molecules. Localization studies of key components of synaptic transmission have confirmed the presence of both presynaptic and postsynaptic proteins at the tight junction domain. To correlate proteomics data with structure, the tight junction has been examined using electron microscopy. This has revealed many novel structures including end-on cytoskeletal attachments, vesicles fusing/budding at the tight junction membrane domain, secreted substances encased between the tight junction kisses, endocytosis of tight junction

  8. Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK.

    Directory of Open Access Journals (Sweden)

    Xiao Xiao Tang

    Full Text Available The tight junctions (TJs, characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK. AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.

  9. Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

    Science.gov (United States)

    Luissint, Anny-Claude; Parkos, Charles A.; Nusrat, Asma

    2017-01-01

    The intestinal tract is lined by a single layer of columnar epithelial cells that forms a dynamic, permeable barrier allowing for selective absorption of nutrients, while restricting access to pathogens and food-borne antigens. Precise regulation of epithelial barrier function is therefore required for maintaining mucosal homeostasis and depends, in part, on barrier-forming elements within the epithelium and a balance between pro- and anti-inflammatory factors in the mucosa. Pathologic states, such as inflammatory bowel disease, are associated with a leaky epithelial barrier, resulting in excessive exposure to microbial antigens, recruitment of leukocytes, release of soluble mediators, and ultimately mucosal damage. An inflammatory microenvironment affects epithelial barrier properties and mucosal homeostasis by altering the structure and function of epithelial intercellular junctions through direct and indirect mechanisms. We review our current understanding of complex interactions between the intestinal epithelium and immune cells, with a focus on pathologic mucosal inflammation and mechanisms of epithelial repair. We discuss leukocyte–epithelial interactions, as well as inflammatory mediators that affect the epithelial barrier and mucosal repair. Increased knowledge of communication networks between the epithelium and immune system will lead to tissue-specific strategies for treating pathologic intestinal inflammation. PMID:27436072

  10. [Prevalence of epithelial squamous cell abnormalities and associated factors in women of a rural town of Colombia].

    Science.gov (United States)

    Grisales, Hugo; Vanegas, Angela Patricia; Gaviria, Angela M; Castaño, Jorge; Mora, Martín Alonso; Borrero, Mauricio; Rojas, Carlos; Arbeláez, María Patricia; Sánchez, Gloria I

    2008-06-01

    In spite of implementation of cytology-based cervical cancer screening in Colombia, mortality rates remain stable. The description of factors associated to cervical pre-neoplasic lesions is needed to establish strategies for mortality prevention. The prevalence of epithelial squamous cell abnormalities was determined to explore the association of cytology abnormalities with described risk factors. This population-based, cross-sectional study included 739 women randomly selected by age. A validated face-to-face questionnaire and conventional cervical cytology were used to collect the information. To establish the association between cervical abnormalities and some qualitative variables, the independent chi squared test was used. We also calculated prevalence ratio with their 95% confidence intervals. A logistic regression model was used to explore variables that potentially explain cytology abnormalities. The prevalence of squamous cell abnormality was 15.8%. Among women with abnormal cytology, 10% presented atypical squamous cells of undetermined significance, 3.9% low grade squamous intra-epithelial lesion and 1.9% high grade squamous intra-epithelial lesion. The adjusted logistical regression analysis showed that history of sexual transmitted disease, two or more sexual partners during entire life and previous abnormal cytology were associated with cytology abnormalities. The relation of epithelial squamous cell abnormalities with sexual behavior history reflexes the link between human papiloma virus infection and cervical cancer pre-neoplasic lesions. The frequency of use and knowledge about the purpose of cytology were factors that suggested other diagnostic limitations such as quality of cervical cytology or barriers to access health care. These latter factors may be the underlying basis for the high cervical cancer mortality rates.

  11. Squamous intraepithelial lesions of the anal squamocolumnar junction: Histopathological classification and HPV genotyping.

    Science.gov (United States)

    Clavero, Omar; McCloskey, Jenny; Molina, Vicente Marco; Quirós, Beatriz; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, F Xavier; Pimenoff, Ville N

    2017-06-01

    Human papillomavirus (HPV)-related anal cancer lesions are often found adjacent to the squamocolumnar junction (SCJ). We have assessed the histopathology and associated HPV genotypes in anal SCJ lesions in surgically excised anal warts in HIV-negative and -positive patients. Histopathology identified 47 squamous intraepithelial lesions (SILs) adjacent to the SCJ amongst a total of 145 cases of clinically diagnosed anal condylomata. The anal SCJ lesions were further analyzed with p16, CK7 and p63 immunohistochemistry and HPV genotyping. Sixteen (16/47) of the excised anal wart lesions contained HSIL; Three were HSIL and exclusively associated with oncogenic HPVs. A further thirteen (13/47) were mixed lesions. Of these eight were HSILs with LSIL and six were HSILs with papillary immature metaplasia (PIM); Ten of the mixed lesions were associated with one or more oncogenic HPVs, while three cases were exclusively associated with HPV6. Clinically diagnosed anal warts cannot be assumed to be limited to low-grade lesions as anal warts of the SCJ often show heterogeneous lesions, with coexistence of LSIL, PIM, and HSIL. Lesions showing PIM, however, may mimic HSIL, because they are hypercellular, but lack the nuclear atypia and conspicuous mitotic activity of HSIL; and are p16 negative. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. GLUT-1 immunoexpression in oral epithelial dysplasia, oral squamous cell carcinoma, and verrucous carcinoma.

    Science.gov (United States)

    Angadi, Vidya C; Angadi, Punnya V

    2015-06-01

    Glucose transporters, such as GLUT-1, mediate the important mechanisms involved in cellular glucose influx, allowing cells to proliferate and survive. The significance of GLUT-1 expression in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) has been less explored, and no study has investigated it in relation to verrucous carcinoma (VC). We evaluated 30 cases each of OED, OSCC, and VC, graded further on the basis of their differentiation, immunohistochemically for GLUT-1 expression, along with 10 specimens of normal oral mucosa (NOM) as controls. In OSCC, GLUT-1 expression increased with the degree of dysplasia and increasing grade (P < 0.001). The expression in VC was predominantly membranous and intense, resembling well differentiated OSCC. This increase of GLUT-1 expression in OSCC along with the degree of dysplasia and the histologic grade reflects the expanding glycolytic response to hypoxia. This is the first study to have revealed prominent GLUT-1 expression in VC, highlighting its inherent metabolic capacity.

  13. Immunohistochemical expression of Bcl-2 in oral epithelial dysplasia and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    S Juneja

    2015-01-01

    Full Text Available BACKGROUND: The B cell lymphoma-2 gene is a proto-oncogene whose protein product inhibits apoptosis. Its role is associated with keeping cells alive, but not by stimulating them to proliferation, as other proto-oncogenes do. Increased expression of protein product of Bcl-2 gene appears in the early phase of carcinogenesis leading to apoptosis impairment and in consequence to the progression of neoplastic changes. OBJECTIVE: To evaluate and compare the expression of Bcl-2 protein in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. MATERIALS AND METHODS: Sixty cases of formalin-fixed paraffin-embedded archival specimens comprising of 30 cases of leukoplakia with oral epithelial dysplasia and 30 cases of OSCC were taken for immunohistochemical analysis using monoclonal antibody against anti-human Bcl-2 oncoprotein. RESULTS: Immunostaining for Bcl-2 protein was identified in basal and parabasal layers as granular cytoplasmic staining in oral epithelial dysplasia. In OSCC, Bcl-2 immunoreactivity was most prominent in the peripheral cells of the infiltrating tumor islands which diminished toward the center in well-differentiated and moderately differentiated OSCC, whereas stronger and more diffuse expression of Bcl-2 oncoprotein was seen in poorly differentiated OSCC. Overall positivity of 26.7% (8/30 was observed in oral epithelial dysplasia and 30% (9/30 in OSCC in this study. INTERPRETATION AND CONCLUSION: Altered expression of Bcl-2 oncoprotein may be an early molecular event which leads to prolonged cell survival, increased chances of accumulation of genetic alterations, and subsequent increase in malignant transformation potential.

  14. Sodium caprate transiently opens claudin-5-containing barriers at tight junctions of epithelial and endothelial cells

    DEFF Research Database (Denmark)

    Del Vecchio, Giovanna; Tscheik, Christian; Tenz, Kareen

    2012-01-01

    Claudin-5 is a tight junction (TJ) protein which limits the diffusion of small hydrophilic molecules. Thus, it represents a potential pharmacological target to improve drug delivery to the tissues protected by claudin-5-dependent barriers. Sodium caprate is known as an absorption enhancer which...... opens the paracellular space acting on TJ proteins and actin cytoskeleton. Its action on claudin-5 is not understood so far. Epithelial and endothelial systems were used to evaluate the effect of caprate on claudin-5 in TJ-free cells and on claudin-5 fully integrated in TJ. To this aim, confocal...... of endothelial and epithelial cells. In conclusion, the study further elucidates the cellular effects of caprate at the tight junctions....

  15. Rho/Rho-associated Kinase-II Signaling Mediates Disassembly of Epithelial Apical Junctions

    OpenAIRE

    2007-01-01

    Apical junctional complex (AJC) plays a vital role in regulation of epithelial barrier function. Disassembly of the AJC is observed in diverse physiological and pathological states; however, mechanisms governing this process are not well understood. We previously reported that the AJC disassembly is driven by the formation of apical contractile acto-myosin rings. In the present study, we analyzed the signaling pathways regulating acto-myosin–dependent disruption of AJC by using a model of ext...

  16. Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions

    Science.gov (United States)

    Sumitomo, Tomoko; Nakata, Masanobu; Higashino, Miharu; Yamaguchi, Masaya; Kawabata, Shigetada

    2016-01-01

    Group A Streptococcus (GAS) is a human-specific pathogen responsible for local suppurative and life-threatening invasive systemic diseases. Interaction of GAS with human plasminogen (PLG) is a salient characteristic for promoting their systemic dissemination. In the present study, a serotype M28 strain was found predominantly localized in tricellular tight junctions of epithelial cells cultured in the presence of PLG. Several lines of evidence indicated that interaction of PLG with tricellulin, a major component of tricellular tight junctions, is crucial for bacterial localization. A site-directed mutagenesis approach revealed that lysine residues at positions 217 and 252 within the extracellular loop of tricellulin play important roles in PLG-binding activity. Additionally, we demonstrated that PLG functions as a molecular bridge between tricellulin and streptococcal surface enolase (SEN). The wild type strain efficiently translocated across the epithelial monolayer, accompanied by cleavage of transmembrane junctional proteins. In contrast, amino acid substitutions in the PLG-binding motif of SEN markedly compromised those activities. Notably, the interaction of PLG with SEN was dependent on PLG species specificity, which influenced the efficiency of bacterial penetration. Our findings provide insight into the mechanism by which GAS exploits host PLG for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. PMID:26822058

  17. Grainy head promotes expression of septate junction proteins and influences epithelial morphogenesis.

    Science.gov (United States)

    Narasimha, Maithreyi; Uv, Anne; Krejci, Alena; Brown, Nicholas H; Bray, Sarah J

    2008-03-15

    Transcription factors of the Grainy head (Grh) family are required in epithelia to generate the impermeable apical layer that protects against the external environment. This function is conserved in vertebrates and invertebrates, despite the differing molecular composition of the protective barrier. Epithelial cells also have junctions that create a paracellular diffusion barrier (tight or septate junctions). To examine whether Grh has a role in regulating such characteristics, we used an epidermal layer in the Drosophila embryo that has no endogenous Grh and lacks septate junctions, the amnioserosa. Expression of Grh in the amnioserosa caused severe defects in dorsal closure, a process similar to wound closure, and induced robust expression of the septate junction proteins Coracle, Fasciclin 3 and Sinuous. Grh-binding sites are present within the genes encoding these proteins, consistent with them being direct targets. Removal of Grh from imaginal disc cells caused a reduction in Fasciclin 3 and Coracle levels, suggesting that Grh normally fine tunes their epithelial expression and hence contributes to barrier properties. The fact that ectopic Grh arrests dorsal closure also suggests that this dynamic process relies on epithelia having distinct adhesive properties conferred by differential deployment of Grh.

  18. Epithelial tricellular junctions act as interphase cell shape sensors to orient mitosis.

    Science.gov (United States)

    Bosveld, Floris; Markova, Olga; Guirao, Boris; Martin, Charlotte; Wang, Zhimin; Pierre, Anaëlle; Balakireva, Maria; Gaugue, Isabelle; Ainslie, Anna; Christophorou, Nicolas; Lubensky, David K; Minc, Nicolas; Bellaïche, Yohanns

    2016-02-25

    The orientation of cell division along the long axis of the interphase cell--the century-old Hertwig's rule--has profound roles in tissue proliferation, morphogenesis, architecture and mechanics. In epithelial tissues, the shape of the interphase cell is influenced by cell adhesion, mechanical stress, neighbour topology, and planar polarity pathways. At mitosis, epithelial cells usually adopt a rounded shape to ensure faithful chromosome segregation and to promote morphogenesis. The mechanisms underlying interphase cell shape sensing in tissues are therefore unknown. Here we show that in Drosophila epithelia, tricellular junctions (TCJs) localize force generators, pulling on astral microtubules and orienting cell division via the Dynein-associated protein Mud independently of the classical Pins/Gαi pathway. Moreover, as cells round up during mitosis, TCJs serve as spatial landmarks, encoding information about interphase cell shape anisotropy to orient division in the rounded mitotic cell. Finally, experimental and simulation data show that shape and mechanical strain sensing by the TCJs emerge from a general geometric property of TCJ distributions in epithelial tissues. Thus, in addition to their function as epithelial barrier structures, TCJs serve as polarity cues promoting geometry and mechanical sensing in epithelial tissues.

  19. TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury.

    Science.gov (United States)

    Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K; Cario, Elke

    2009-08-14

    Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1alpha-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair.

  20. Architectural Analysis of Picrosirius Red Stained Collagen in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma using Polarization Microscopy

    Science.gov (United States)

    Sharma, Rashi; Rehani, Shweta; Mehendiratta, Monica; Kumra, Madhumani; Mathias, Yulia; Yadav, Jyoti; Sahay, Khushboo

    2015-01-01

    Introduction Collagen degradation is important both for carcinogenesis and in its progression. Research regarding the co-relation of collagen with Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC) is less explored. Aim To elucidate the nature of collagen in Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC) using Picrosirius Red Stain (PSR) under polarizing microscopy. Materials and Methods The study consisted of a total 40 samples which were divided into three groups. Group I included buccal mucosa as negative and irritation fibroma as positive control, group II consisted of OED and group III consisted of Oral Squamous Cell Carcinoma (OSCC). A histochemical analysis was conducted using PSR-polarization method by two independent observers. Results The control group shows predominantly reddish–orange birefringence. In OED with the advancement of grades, the colour changed from yellowish-orange colour to yellow-greenish with progressive increase in greenish hue. As OSCC regresses from well to poorly differentiated, the colour changed from reddish-orange to yellowish orange to greenish-yellow suggesting a transition from mature to immature collagen. Conclusion An observable gradual change in collagen of both OED and OSCC was noted as they were proceeding from benign to critical step. Thus, PSR is a useful tool for studying stromal changes as supporting collagen shows the transition in the form besides the alterations in epithelial cells. PMID:26816897

  1. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Science.gov (United States)

    Sufiawati, Irna; Tugizov, Sharof M

    2014-01-01

    Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  2. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Directory of Open Access Journals (Sweden)

    Irna Sufiawati

    Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  3. Suprabasal expression of Ki-67 as a marker for the severity of oral epithelial dysplasia and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Nidhi Dwivedi

    2013-01-01

    Full Text Available Background: Transition of the normal oral epithelium to dysplasia and to malignancy is featured by increased cell proliferation. To evaluate the hypothesis of distributional disturbances in proliferating and stem cells in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. Aim: To evaluate layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC. Materials and Methods: Thirty histologically confirmed cases of oral epithelial dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were immunohistochemically examined and nuclear expression of Ki-67 was counted according to basal, parabasal, and suprabasal layers in epithelial dysplasia and number of positive cells per 100 cells in OSCC as labeling index (LI. Results: Suprabasal expression of Ki-67 increased according to the severity of epithelial dysplasia and the difference was statistically significant ( P < 0.001. The mean Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for OSCC and 13.6 for normal buccal mucosa. Conclusion: The results of the present study demonstrate the use of proliferative marker Ki-67 in assessing the severity of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective criteria for determining the severity of epithelial dysplasia and histological grading of OSCC.

  4. Immunohistochemical Evaluation of Glucose Transporter Type 1 in Epithelial Dysplasia and Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Pereira, Karuza Maria Alves; Feitosa, Sthefane Gomes; Lima, Ana Thayssa Tomaz; Luna, Ealber Carvalho Macedo; Cavalcante, Roberta Barroso; de Lima, Kenio Costa; Chaves, Filipe Nobre; Costa, Fábio Wildson Gurgel

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and some of these have been documented in association or preceded by oral epithelial dysplasia (OED). Aggressive cancers with fast growth have demonstrated overexpression of some glucose transporters (GLUTs). Thus, the aim of this study was to analyze the immunohistochemical expression of the glucose transporter, GLUT-1, in OEDs and OSCCs, seeking to better elucidate the biological behavior of neoplasias. Fifteen cases were selected this research of both lesions. Five areas were analyzed from each case by counting the percentage of positive cells at 400x magnification. Immunoreactivity of GLUT-1 was observed in 100% of the samples ranging from 54.2% to 86.2% for the OSCC and 73.9% to 97.4% for the OED. Statistical test revealed that there was greater overexpression of GLUT-1 in OED than the OSCC (p=0.01). It is believed the high expression of GLUT-1 may reflect the involvement of GLUT-1 in early stages of oral carcinogenesis.

  5. Transcutaneous carbon dioxide suppresses epithelial-mesenchymal transition in oral squamous cell carcinoma.

    Science.gov (United States)

    Iwata, Eiji; Hasegawa, Takumi; Takeda, Daisuke; Ueha, Takeshi; Kawamoto, Teruya; Akisue, Toshihiro; Sakai, Yoshitada; Komori, Takahide

    2016-04-01

    Oral squamous cell carcinoma (OSCC) is the most common form of oral cancers. Recent studies have shown that the malignant transformation of various carcinomas, including OSCC, is associated with epithelial-mesenchymal transition (EMT), and that expression of the EMT factors are significantly associated with tumor invasion, tumor metastasis, and survival rates in OSCC patients. Hence, there is a possibility that EMT suppression may improve the prognosis of OSCC patients. Hypoxia inducible factor-1α (HIF-1α) is a crucial microenvironmental factor in tumor progression, which induces the expression of EMT factors. We previously reported that transcutaneous CO2 suppresses both human OSCC tumor growth and metastasis to the regional lymph nodes by improving hypoxia in treated tissue. According to this background, we hypothesized that increased EMT with HIF-1α expression may increase the progression and the metastatic potential of OSCC, and that decreased hypoxia by transcutaneous CO2 could suppress EMT. In the present study, in vitro studies showed that hypoxic conditions increased the expression of HIF-1α and EMT factors in OSCC cells. In addition, in vivo studies revealed that transcutaneous CO2 increased E-cadherin expression with the decreased expression of HIF-1α, Snail, Slug, N-cadherin, and Vimentin in tumor treatment. These results suggest that transcutaneous CO2 could suppress EMT by improving hypoxia, resulting in the reduction of metastatic potential of OSCC. The findings indicate that transcutaneous CO2 may be able to improve the prognosis of OSCC patients through the suppression of EMT.

  6. Tracking epithelial cell junctions in C. elegans embryogenesis with active contours guided by SIFT flow.

    Science.gov (United States)

    Kang, Sukryool; Lee, Chen-Yu; Gonçalves, Monira; Chisholm, Andrew D; Cosman, Pamela C

    2015-04-01

    Quantitative analysis of cell shape in live samples is an important goal in developmental biology. Automated or semi-automated segmentation and tracking of cell nuclei has been successfully implemented in several biological systems. Segmentation and tracking of cell surfaces has been more challenging. Here, we present a new approach to tracking cell junctions in the developing epidermis of C. elegans embryos. Epithelial junctions as visualized with DLG-1::GFP form lines at the subapical circumference of differentiated epidermal cells and delineate changes in epidermal cell shape and position. We develop and compare two approaches for junction segmentation. For the first method (projection approach), 3-D cell boundaries are projected into 2D for segmentation using active contours with a nonintersecting force, and subsequently tracked using scale-invariant feature transform (SIFT) flow. The resulting 2-D tracked boundaries are then back-projected into 3-D space. The second method (volumetric approach) uses a 3-D extended version of active contours guided by SIFT flow in 3-D space. In both methods, cell junctions are manually located at the first time point and tracked in a fully automated way for the remainder of the video. Using these methods, we have generated the first quantitative description of ventral epidermal cell movements and shape changes during epidermal enclosure.

  7. Protein tyrosine phosphatase σ targets apical junction complex proteins in the intestine and regulates epithelial permeability.

    Science.gov (United States)

    Murchie, Ryan; Guo, Cong-Hui; Persaud, Avinash; Muise, Aleixo; Rotin, Daniela

    2014-01-14

    Protein tyrosine phosphatase (PTP)σ (PTPRS) was shown previously to be associated with susceptibility to inflammatory bowel disease (IBD). PTPσ(-/-) mice exhibit an IBD-like phenotype in the intestine and show increased susceptibility to acute models of murine colitis. However, the function of PTPσ in the intestine is uncharacterized. Here, we show an intestinal epithelial barrier defect in the PTPσ(-/-) mouse, demonstrated by a decrease in transepithelial resistance and a leaky intestinal epithelium that was determined by in vivo tracer analysis. Increased tyrosine phosphorylation was observed at the plasma membrane of epithelial cells lining the crypts of the small bowel and colon of the PTPσ(-/-) mouse, suggesting the presence of PTPσ substrates in these regions. Using mass spectrometry, we identified several putative PTPσ intestinal substrates that were hyper-tyrosine-phosphorylated in the PTPσ(-/-) mice relative to wild type. Among these were proteins that form or regulate the apical junction complex, including ezrin. We show that ezrin binds to and is dephosphorylated by PTPσ in vitro, suggesting it is a direct PTPσ substrate, and identified ezrin-Y353/Y145 as important sites targeted by PTPσ. Moreover, subcellular localization of the ezrin phosphomimetic Y353E or Y145 mutants were disrupted in colonic Caco-2 cells, similar to ezrin mislocalization in the colon of PTPσ(-/-) mice following induction of colitis. Our results suggest that PTPσ is a positive regulator of intestinal epithelial barrier, which mediates its effects by modulating epithelial cell adhesion through targeting of apical junction complex-associated proteins (including ezrin), a process impaired in IBD.

  8. Segmentation and tracking of adherens junctions in 3D for the analysis of epithelial tissue morphogenesis.

    Science.gov (United States)

    Cilla, Rodrigo; Mechery, Vinodh; Hernandez de Madrid, Beatriz; Del Signore, Steven; Dotu, Ivan; Hatini, Victor

    2015-04-01

    Epithelial morphogenesis generates the shape of tissues, organs and embryos and is fundamental for their proper function. It is a dynamic process that occurs at multiple spatial scales from macromolecular dynamics, to cell deformations, mitosis and apoptosis, to coordinated cell rearrangements that lead to global changes of tissue shape. Using time lapse imaging, it is possible to observe these events at a system level. However, to investigate morphogenetic events it is necessary to develop computational tools to extract quantitative information from the time lapse data. Toward this goal, we developed an image-based computational pipeline to preprocess, segment and track epithelial cells in 4D confocal microscopy data. The computational pipeline we developed, for the first time, detects the adherens junctions of epithelial cells in 3D, without the need to first detect cell nuclei. We accentuate and detect cell outlines in a series of steps, symbolically describe the cells and their connectivity, and employ this information to track the cells. We validated the performance of the pipeline for its ability to detect vertices and cell-cell contacts, track cells, and identify mitosis and apoptosis in surface epithelia of Drosophila imaginal discs. We demonstrate the utility of the pipeline to extract key quantitative features of cell behavior with which to elucidate the dynamics and biomechanical control of epithelial tissue morphogenesis. We have made our methods and data available as an open-source multiplatform software tool called TTT (http://github.com/morganrcu/TTT).

  9. Proteomic Comparison of Two-Dimensional Gel Electrophoresis Pro files from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    Cui Li; Ping Chen; Jingyun Xie; Songping Liang; Xianquan Zhan; Maoyu Li; Xiaoying Wu; Feng Li; Jianling Li; Zhiqiang Xiao; Zhuchu Chen; Xueping Feng

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-ug protein-load. The average deviation of spot position was 0.733+0.101 mm in IEF direction, and 0.925+0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190+72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls.Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduction. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  10. Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation*

    Science.gov (United States)

    Sumitomo, Tomoko; Nakata, Masanobu; Higashino, Miharu; Terao, Yutaka; Kawabata, Shigetada

    2013-01-01

    Group A Streptococcus (GAS) is an important human pathogen that possesses an ability to translocate across the epithelial barrier. In this study, culture supernatants of tested GAS strains showed proteolytic activity against human occludin and E-cadherin. Utilizing various types of protease inhibitors and amino acid sequence analysis, we identified SpeB (streptococcal pyrogenic exotoxin B) as the proteolytic factor that cleaves E-cadherin in the region neighboring the calcium-binding sites within the extracellular domain. The cleaving activities of culture supernatants from several GAS isolates were correlated with the amount of active SpeB, whereas culture supernatants from an speB mutant showed no such activities. Of note, the wild type strain efficiently translocated across the epithelial monolayer along with cleavage of occludin and E-cadherin, whereas deletion of the speB gene compromised those activities. Moreover, destabilization of the junctional proteins was apparently relieved in cells infected with the speB mutant, as compared with those infected with the wild type. Taken together, our findings indicate that the proteolytic efficacy of SpeB in junctional degradation allows GAS to invade deeper into tissues. PMID:23532847

  11. Expression of epithelial-mesenchymal transition markers at the invasive front of oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Liana Cristina Melo Carneiro COSTA

    2015-04-01

    Full Text Available Oral squamous cell carcinoma (OSCC is one of the most common malignances. In epithelial-mesenchymal transition (EMT, epithelial cells switch to mesenchymal-like cells exhibiting high mobility. This migratory phenotype is significant during tumor invasion and metastasis. Objective : The aim of this study is to evaluate the expression of the EMT markers E-cadherin, N-cadherin and vimentin in OSCC. Material and Methods : Immunohistochemical detection of E-cadherin, N-cadherin and vimentin was performed on 20 OSCC samples. Differences in the expression of each protein at the invasive front (IF and in the central/superficial areas (CSA of the tumor were assessed. Differences in the expression of each protein at the IF of both histologically high- and low-invasive OSCCs were evaluated. Associations among expression of proteins at the IF were assessed. Correlations between the expression levels of each protein at the IF and the tumor stage and clinical nodal status were also evaluated. Results : Reduced expression of E-cadherin was detected in 15 samples (75%. E-cadherin expression was reduced at the IF when compared to the CSA and in high-invasive tumors when compared to low-invasive tumors. All samples were negative for N-cadherin, even though one sample showed an inconspicuous expression. Positive expression of vimentin was observed in 6 samples (30%. Nevertheless, there was no difference in vimentin expression between the IF and the CSA regions or between the low- and high-invasive tumors. Furthermore, no association was observed among protein expression levels at the IF. Finally, no correlations were observed between each protein’s expression levels and tumor stage or clinical nodal status. Conclusions : Reduced E-cadherin expression at the IF and its association with histological invasiveness suggest that this protein is a noteworthy EMT marker in OSCC. Although vimentin was also detected as an EMT marker, its expression was neither limited to

  12. TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kaile Wu

    2016-11-01

    Full Text Available Background/Aim: Surgery and chemotherapy treatments of human laryngeal squamous cell carcinoma (HLSCC may fail due to metastasis, in which epithelial-mesenchymal transition (EMT plays an important role. TRPP2, a nonselective cation channel, is expressed in various cell types and participates in many biological processes. Here, we show that TRPP2 enhanced metastasis by regulating EMT. Methods: We used immunohistochemistry, western blotting, Ca2+ imaging, transwell and wound healing assays to investigate TRPP2 expression levels in HLSCC tissue, and the role of TRPP2 in invasion and metastasis of a human laryngocarcinoma cell line (Hep2 cell. Results: We found that TRPP2 protein expression levels were significantly increased in HLSCC tissue; higher TRPP2 levels were associated with decreased patient survival time and degree of differentiation and advanced clinical stage. Knockdown of TRPP2 by transfection with TRPP2 siRNA markedly suppressed ATP-induced Ca2+ release, wound healing, and cell invasion in Hep2 cells. Moreover, TRPP2 siRNA significantly decreased vimentin expression but increased E-cadherin expression in Hep2 cells. In the EMT signalling pathway, TRPP2 siRNA significantly decreased Smad4, STAT3, SNAIL, SLUG and TWIST expression in Hep2 cells. Conclusion: We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC.

  13. Phenotypic plasticity and epithelial-to-mesenchymal transition in the behaviour and therapeutic response of oral squamous cell carcinoma.

    Science.gov (United States)

    Vig, Navin; Mackenzie, Ian C; Biddle, Adrian

    2015-10-01

    It is increasingly recognised that phenotypic plasticity, apparently driven by epigenetic mechanisms, plays a key role in tumour behaviour and markedly influences the important processes of therapeutic survival and metastasis. An important source of plasticity in malignancy is epithelial-to-mesenchymal transition (EMT), a common epigenetically controlled event that results in transition of malignant cells between different phenotypic states that confer motility and enhance survival. In this review, we discuss the importance of phenotypic plasticity and its contribution to cellular heterogeneity in oral squamous cell carcinoma with emphasis on aspects of drug resistance and EMT.

  14. Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells.

    Science.gov (United States)

    Sunpaweravong, S; Sunpaweravong, P; Sathitruangsak, C; Mai, S

    2016-05-01

    Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P architecture and found no statistically significant differences in any parameter tested between the young and old patients in either the tumor or epithelial cells. The 3D nuclear telomeric signature was able to detect differences in telomere architecture

  15. Proteomic Comparison of Two—Dimensional Gel Electrophoresis Profiles from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    CuiLi; XianquanZhan; MaoyuLi; XiaoyingWu; FengLi; JianlingLi; ZhiqiangXiao; ZhuchuChen; XuepingFeng; PingChen; JingyunXie; SongpingLiang

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis(2-D PAGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS).The results showed that well-resolved,reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load.The average deviation of spot position was 0.733±0.101 mm in IEF direction,and 0.925±0.207mm in SDS-PAGE direction.For tumor tissue,a total of 1241±88 spots were detected,987±65 spots were matched with an average matching rate of 79.5%.For control,a total of 1190±72 spots were detected,and 875±48 spots were matched with an average matching rate of 73.5%.A total of 864±34 spots were matched between tumors and controls.Forth-three differential proteins were characterized:some proteins were related to oncogenes,and others involved in the regulation of cell cycle and signal transduction.It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  16. Autophagy enhances intestinal epithelial tight junction barrier function by targeting claudin-2 protein degradation.

    Science.gov (United States)

    Nighot, Prashant K; Hu, Chien-An Andy; Ma, Thomas Y

    2015-03-13

    Autophagy is an intracellular degradation pathway and is considered to be an essential cell survival mechanism. Defects in autophagy are implicated in many pathological processes, including inflammatory bowel disease. Among the innate defense mechanisms of intestinal mucosa, a defective tight junction (TJ) barrier has been postulated as a key pathogenic factor in the causation and progression of inflammatory bowel disease by allowing increased antigenic permeation. The cross-talk between autophagy and the TJ barrier has not yet been described. In this study, we present the novel finding that autophagy enhances TJ barrier function in Caco-2 intestinal epithelial cells. Nutrient starvation-induced autophagy significantly increased transepithelial electrical resistance and reduced the ratio of sodium/chloride paracellular permeability. Nutrient starvation reduced the paracellular permeability of small-sized urea but not larger molecules. The role of autophagy in the modulation of paracellular permeability was confirmed by pharmacological induction as well as pharmacological and genetic inhibition of autophagy. Consistent with the autophagy-induced reduction in paracellular permeability, a marked decrease in the level of the cation-selective, pore-forming TJ protein claudin-2 was observed after cell starvation. Starvation reduced the membrane presence of claudin-2 and increased its cytoplasmic, lysosomal localization. Therefore, our data show that autophagy selectively reduces epithelial TJ permeability of ions and small molecules by lysosomal degradation of the TJ protein claudin-2.

  17. Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.

    Science.gov (United States)

    Patkee, Wishwanath R A; Carr, Georgina; Baker, Emma H; Baines, Deborah L; Garnett, James P

    2016-04-01

    Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics.

  18. Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas

    DEFF Research Database (Denmark)

    Nielsen, P A; Mandel, U; Therkildsen, M H

    1997-01-01

    layers of buccal epithelium and was also found in larynx, esophagus, vagina, and exocervix, but not in epidermis. Data showed that gp230 was distinct from MUC1 or CD44. It is interesting that in most cases gp230 was not expressed in squamous cell carcinomas of buccal and cervical mucosa. A few moderately...

  19. Characterization of the tight junction protein ZO-2 localized at the nucleus of epithelial cells.

    Science.gov (United States)

    Jaramillo, Blanca Estela; Ponce, Arturo; Moreno, Jacqueline; Betanzos, Abigail; Huerta, Miriam; Lopez-Bayghen, Esther; Gonzalez-Mariscal, Lorenza

    2004-07-01

    ZO-2 is a MAGUK protein that in confluent epithelial sheets localizes at tight junctions (TJ) whereas in sparse cultures accumulates in clusters at the nucleus. Here, we have characterized several nuclear properties of ZO-2. We observe that ZO-2 is present in the nuclear matrix and co-immunoprecipitates with lamin B(1) and actin from the nuclei of sparse cultures. We show that ZO-2 presents several NLS at its amino region, that when deleted, diminish the nuclear import of the ZO-2 amino segment and impair the ability of the region to regulate the transcriptional activity of promoters controlled by AP-1. Several RS repeats are detected in the ZO-2 amino segment, however, their deletion does not preclude the display of a speckled nuclear pattern. ZO-2 displays two putative NES. However, only the second one appears to be functional, as when conjugated to ovalbumin (OV), it is able to translocate this protein from the nucleus to the cytoplasm in a leptomycin B-sensitive way.

  20. Oct4 mediates tumor initiating properties in oral squamous cell carcinomas through the regulation of epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Lo-Lin Tsai

    Full Text Available BACKGROUND: Overexpression of Oct4, an important transcription factor of embryonic stem cells (ESC, has been reported in several cancers. The aim of this study was to determine the emerging role of Oct4 in oral squamous cell carcinoma (OSCC both in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDING: Tumourigenic activity and molecular mechanisms of Oct4 overexpression or knockdown by lentiviral infection in OSCC was investigated in vitro and in vivo. Initially, we demonstrated that Oct4 expression was increased in OSCC cell lines as compared to a normal oral epithelial cell line SG. Overexpression of Oct4 was demonstrated to enhance cell proliferation, invasiveness, anchorage-independent growth and xenotransplantation tumourigenicity. These findings were coupled with epithelial-mesenchymal transition (EMT transformation in OSCCs. In contrast, the silence of Oct4 significantly blocked the xenograft tumorigenesis of OSCC-derived cancer stem cells (OSCC-CSCs and significantly improved the recipient survival. Clinically, the level of Oct4 expression was higher in recurrent and metastatic OSCC specimens but lower in primary OSCC specimens. CONCLUSION/SIGNIFICANCE: Our results suggest that Oct4-mediated tumorigenecity is associated with the regulation of EMT. Oct4 might be a therapeutic target for OSCC.

  1. Effect of FCCP on tight junction permeability and cellular distribution of ZO-1 protein in epithelial (MDCK) cells.

    Science.gov (United States)

    Li, C X; Poznansky, M J

    1990-12-14

    The effect of the uncoupler of oxidative phosphorylation, FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone), on the tight junction of Madin-Darby canine kidney cells was examined. FCCP induced an abrupt decrease in the transepithelial electrical resistance of the confluent monolayers over a period of 20 s. When FCCP was withdrawn from the incubation medium, the monolayer resistance recovered to close to the original level in less than 2 h. Staining of the tight junction-associated protein ZO-1 showed that the changes in transepithelial electrical resistance were accompanied by a diffusing of the protein away from cell peripheries and a reconcentration to the tight junction areas following resistance recovery. Intracellular pH was decreased by FCCP on a similar time-scale with no obvious changes in ATP levels over this time-course. These data suggest that the uncoupler FCCP has a profound effect on tight junction permeability and cellular distribution of the tight junction protein ZO-1 in the epithelial cells and that it probably acts by breaking down proton gradients and altering intracellular pH.

  2. L. plantarum prevents Enteroinvasive Escherichia coli-induced tight junction proteins changes in intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Hang Xiaomin

    2009-03-01

    Full Text Available Abstract Background It is increasingly recognized that Lactobacillus plantarum (L. plantarum has the ability to protect against Enteropathogenic Escherichia coli (EPEC-induced damage of the epithelial monolayer barrier function by preventing changes in host cell morphology, attaching/effacing (A/E lesion formation, monolayer resistance, and macromolecular permeability. However, the cellular mechanism involved in this protective effect still remained to be clarified. Methods This study was to investigate the effect of L. plantarum on the changes of Caco-2 cells responding to Enteroinvasive Escherichia coli (EIEC, the permeability of cell monolayer and the transmissivity of dextran, and the distribution and expression of the tight junction (TJ proteins, such as Claudin-1, Occludin, JAM-1 and ZO-1 were examined when infected with EIEC or adhesived of L. plantarum after infection by confocal laser scanning microscopy (CLSM, immunohistochemistry and Western blotting, the cytoskeleton protein F-actin were observed with FITC-phalloidin. Results This study demonstrated that the transepithelial electrical resistance (TER step down and dextran integrated intensity (DII step up with time after infected with EIEC, but after treating with L. plantarum, the changes of TER and DII were improved as compared with EIEC group. L. plantarum prevented the damage of expression and rearrangement of Claudin-1, Occludin, JAM-1 and ZO-1 proteins induced by EIEC, and could ameliorate the injury of cytoskeleton protein F-actin infected with EIEC. Conclusion L. plantarum exerted a protective effect against the damage to integrity of Caco-2 monolayer cells and the structure and distribution of TJ proteins by EIEC infection.

  3. Escherichia coli STb enterotoxin dislodges claudin-1 from epithelial tight junctions.

    Directory of Open Access Journals (Sweden)

    Hassan Nassour

    Full Text Available Enterotoxigenic Escherichia coli produce various heat-labile and heat-stable enterotoxins. STb is a low molecular weight heat-resistant toxin responsible for diarrhea in farm animals, mainly young pigs. A previous study demonstrated that cells having internalized STb toxin induce epithelial barrier dysfunction through changes in tight junction (TJ proteins. These modifications contribute probably to the diarrhea observed. To gain insight into the mechanism of increased intestinal permeability following STb exposure we treated human colon cells (T84 with purified STb toxin after which cells were harvested and proteins extracted. Using a 1% Nonidet P-40-containing solution we investigated the distribution of claudin-1, a major structural and functional TJ protein responsible for the epithelium impermeability, between membrane (NP40-insoluble and the cytoplasmic (NP-40 soluble location. Using immunoblot and confocal microscopy, we observed that treatment of T84 cell monolayers with STb induced redistribution of claudin-1. After 24 h, cells grown in Ca++-free medium treated with STb showed about 40% more claudin-1 in the cytoplasm compare to the control. Switching from Ca++-free to Ca++-enriched medium (1.8 mM increased the dislodgement rate of claudin-1 as comparable quantitative delocalization was observed after only 6 h. Medium supplemented with the same concentration of Mg++ or Zn++ did not affect the dislodgement rate compared to the Ca++-free medium. Using anti-phosphoserine and anti-phosphothreonine antibodies, we observed that the loss of membrane claudin-1 was accompanied by dephosphorylation of this TJ protein. Overall, our findings showed an important redistribution of claudin-1 in cells treated with STb toxin. The loss of phosphorylated TJ membrane claudin-1 is likely to be involved in the increased permeability observed. The mechanisms by which these changes are brought about remain to be elucidated.

  4. Escherichia coli STb enterotoxin dislodges claudin-1 from epithelial tight junctions.

    Science.gov (United States)

    Nassour, Hassan; Dubreuil, J Daniel

    2014-01-01

    Enterotoxigenic Escherichia coli produce various heat-labile and heat-stable enterotoxins. STb is a low molecular weight heat-resistant toxin responsible for diarrhea in farm animals, mainly young pigs. A previous study demonstrated that cells having internalized STb toxin induce epithelial barrier dysfunction through changes in tight junction (TJ) proteins. These modifications contribute probably to the diarrhea observed. To gain insight into the mechanism of increased intestinal permeability following STb exposure we treated human colon cells (T84) with purified STb toxin after which cells were harvested and proteins extracted. Using a 1% Nonidet P-40-containing solution we investigated the distribution of claudin-1, a major structural and functional TJ protein responsible for the epithelium impermeability, between membrane (NP40-insoluble) and the cytoplasmic (NP-40 soluble) location. Using immunoblot and confocal microscopy, we observed that treatment of T84 cell monolayers with STb induced redistribution of claudin-1. After 24 h, cells grown in Ca++-free medium treated with STb showed about 40% more claudin-1 in the cytoplasm compare to the control. Switching from Ca++-free to Ca++-enriched medium (1.8 mM) increased the dislodgement rate of claudin-1 as comparable quantitative delocalization was observed after only 6 h. Medium supplemented with the same concentration of Mg++ or Zn++ did not affect the dislodgement rate compared to the Ca++-free medium. Using anti-phosphoserine and anti-phosphothreonine antibodies, we observed that the loss of membrane claudin-1 was accompanied by dephosphorylation of this TJ protein. Overall, our findings showed an important redistribution of claudin-1 in cells treated with STb toxin. The loss of phosphorylated TJ membrane claudin-1 is likely to be involved in the increased permeability observed. The mechanisms by which these changes are brought about remain to be elucidated.

  5. Matrix metalloproteinase-9-deficient dendritic cells have impaired migration through tracheal epithelial tight junctions.

    Science.gov (United States)

    Ichiyasu, Hidenori; McCormack, Joanne M; McCarthy, Karin M; Dombkowski, David; Preffer, Frederic I; Schneeberger, Eveline E

    2004-06-01

    When sampling inhaled antigens, dendritic cells (DC) must penetrate the tight junction (TJ) barrier while maintaining the TJ seal. In matrix metalloproteinase (MMP)-9-deficient mice, in vivo experiments suggest that migration of DC into air spaces is impaired. To examine the underlying mechanisms, we established a well-defined in vitro model using mouse tracheal epithelial cells and mouse bone marrow DC (BMDC). Transmigration was elicited with either macrophage inflammatory protein (MIP)-1alpha or MIP-3beta in a time-dependent manner. Control MMP-9(+/+) BMDC cultured with granulocyte macrophage-colony-stimulating factor for 7 d showed a 30-fold greater transepithelial migration toward MIP-3beta than MIP-1alpha, indicating a more mature DC phenotype. MMP-9(-/-) BMDC as well as MMP-9(+/+) BMDC in the presence of the MMP inhibitor GM6001, although showing a similar preference for MIP-3beta, were markedly impaired in their ability to traverse the epithelium. Expression levels of CCR5 and CCR7, however, were similar in both MMP-9(-/-) and MMP-9(+/+) BMDC. Expression of the integral TJ proteins, occludin and claudin-1, were examined in BMDC before and after transepithelial migration. Interestingly, occludin but not claudin-1 was degraded following transepithelial migration in both MMP-9(-/-) and control BMDC. In addition, there was a > 2-fold increase in claudin-1 expression in MMP-9(-/-) as compared with control BMDC. These observations indicate that occludin and claudin-1 are differentially regulated and suggest that the lack of MMP-9 may affect claudin-1 turnover.

  6. Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)

    Science.gov (United States)

    Pectasides, Eirini; Rampias, Theodoros; Sasaki, Clarence; Perisanidis, Christos; Kouloulias, Vassilis; Burtness, Barbara; Zaramboukas, Thomas; Rimm, David; Fountzilas, George; Psyrri, Amanda

    2014-01-01

    Background Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis. Methods Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA). We evaluated associations with clinicopathological parameters and prognosis. Results There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04) and overall survival (OS) (69.6% versus 44.3%, p  = 0.05). Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards significance for OS. Conclusions The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis. PMID:24722213

  7. Markers of epithelial to mesenchymal transition in association with survival in head and neck squamous cell carcinoma (HNSCC.

    Directory of Open Access Journals (Sweden)

    Eirini Pectasides

    Full Text Available BACKGROUND: Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC prognosis. METHODS: Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA. We evaluated associations with clinicopathological parameters and prognosis. RESULTS: There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04 and overall survival (OS (69.6% versus 44.3%, p  = 0.05. Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057. High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029. In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046 while EGFR trended towards significance for OS. CONCLUSIONS: The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis.

  8. Alpha-catenin-Dependent Recruitment of the Centrosomal Protein CAP350 to Adherens Junctions Allows Epithelial Cells to Acquire a Columnar Shape

    Science.gov (United States)

    Zurbano, Angel; Formstecher, Etienne; Martinez-Morales, Juan R.; Bornens, Michel; Rios, Rosa M.

    2015-01-01

    Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis. PMID:25764135

  9. p53 and p16 in oral epithelial dysplasia and oral squamous cell carcinoma: A study of 208 cases

    Directory of Open Access Journals (Sweden)

    Juan C Cuevas Gonzalez

    2016-01-01

    Full Text Available Background: The use of p16 and p53 as biomarkers of malignant transformation of oral epithelial dysplasia (OED and biological behavior of oral squamous cell carcinoma (OSCC is controversial. Aim: To determine the immunoexpression of p16 and p53 in OED and OSCC and to establish their possible relation to histopathological grading of OED/OSCC. Materials and Methods: Ninety-six OEDs (40 mild, 36 moderate, and 20 severe dysplasia; and 112 OSCCs (64 well-differentiated, 38 moderately differentiated, and 10 poorly differentiated coming from archives of four centers of oral pathology were included. Histological slides from all cases were processed with immunohistochemical technique using anti-p53 and anti-p16 antibodies. The intensity of the immunoreactivity were classified using the ImageLab®MCM systemas follows: 60–90 strong. Forstatistical purposesa χ2 test (P 0.05. Statistical association of p16-positive and p53-positive cells to basal stratum of OED (P = 0.0008; P = 0.0000, respectively and p16-positive cells and p53-positive cells to perivascular zone of OSCC (P = 0.001; P = 0.0000, respectively was found. Conclusions: p16 and p53 could be not specific enough to identify patients suffering OED with high risk to malignancy; however, the evaluation of the presence of p16 and p53 in the tumoral invasive front of OSCC could contribute to establish the tumor progression.

  10. Heat shock protein 47 expression in oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells.

    Science.gov (United States)

    Lee, Shiuan-Shinn; Tseng, Ling-Hsien; Li, Yi-Ching; Tsai, Chung-Hung; Chang, Yu-Chao

    2011-05-01

    Heat shock protein 47 (HSP47) is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of this study was to compare HSP47 expression in normal human oral epithelium and OSCC and further to explore the potential mechanisms that may lead to induce HSP47 expression. Thirty-two OSCC specimens and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line OC2 cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N-acetyl-l-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, cyclooxygenase-2 inhibitor NS-398, and tyrosine kinase inhibitor herbimycin A were added to find the possible regulatory mechanisms. HSP47 expression was significantly higher in OSCC specimens than normal epithelium (P0.05). The lower HSP47 expression was associated with lymph node metastasis (P=0.015). Arecoline was found to elevate HSP47 expression in a dose- and time-dependent manner (Parecoline-induced HSP47 expression (Parecoline-induced HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and herbimycin A. © 2010 John Wiley & Sons A/S.

  11. Structural Molecular Components of Septate Junctions in Cnidarians Point to the Origin of Epithelial Junctions in Eukaryotes

    KAUST Repository

    Ganot, P.

    2014-09-21

    Septate junctions (SJs) insure barrier properties and control paracellular diffusion of solutes across epithelia in invertebrates. However, the origin and evolution of their molecular constituents in Metazoa have not been firmly established. Here, we investigated the genomes of early branching metazoan representatives to reconstruct the phylogeny of the molecular components of SJs. Although Claudins and SJ cytoplasmic adaptor components appeared successively throughout metazoan evolution, the structural components of SJs arose at the time of Placozoa/Cnidaria/Bilateria radiation. We also show that in the scleractinian coral Stylophora pistillata, the structural SJ component Neurexin IV colocalizes with the cortical actin network at the apical border of the cells, at the place of SJs. We propose a model for SJ components in Cnidaria. Moreover, our study reveals an unanticipated diversity of SJ structural component variants in cnidarians. This diversity correlates with gene-specific expression in calcifying and noncalcifying tissues, suggesting specific paracellular pathways across the cell layers of these diploblastic animals.

  12. Evolution and cell physiology. 4. Why invent yet another protein complex to build junctions in epithelial cells?

    Science.gov (United States)

    Le Bivic, André

    2013-12-15

    The formation of the first epithelium was an essential step for animal evolution, since it has allowed coordination of the behavior of a cell layer and creation of a selective barrier between the internal medium and the outside world. The possibility of coupling the cells in a single layer has allowed morphogenetic events, such as tube formation, or gastrulation, to form more complex animal morphologies. The invention of sealed junctions between cells has allowed, on the other hand, creation of an asymmetry of nutrients or salts between the apical and the basal side of the epithelial layer. Creation of an internal medium has led to homeostasis, allowing the evolution of more complex physiological functions and the emergence of sophisticated animal shapes. During evolution, the origins of the first animals coincided with the invention of several protein complexes, including true cadherins and the polarity protein complexes. How these complexes regulate formation of the apicolateral border and the adherens junctions is still not fully understood. This review focuses on the role of these apical polarity complexes and, in particular, the Crumbs complex, which is essential for proper organization of epithelial layers from Drosophila to humans.

  13. Pseudomonas aeruginosa Transmigrates at Epithelial Cell-Cell Junctions, Exploiting Sites of Cell Division and Senescent Cell Extrusion.

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    Guillaume Golovkine

    2016-01-01

    Full Text Available To achieve systemic infection, bacterial pathogens must overcome the critical and challenging step of transmigration across epithelial barriers. This is particularly true for opportunistic pathogens such as Pseudomonas aeruginosa, an agent which causes nosocomial infections. Despite extensive study, details on the mechanisms used by this bacterium to transmigrate across epithelial tissues, as well as the entry sites it uses, remain speculative. Here, using real-time microscopy and a model epithelial barrier, we show that P. aeruginosa employs a paracellular transmigration route, taking advantage of altered cell-cell junctions at sites of cell division or when senescent cells are expelled from the cell layer. Once a bacterium transmigrates, it is followed by a cohort of bacteria using the same entry point. The basal compartment is then invaded radially from the initial penetration site. Effective transmigration and propagation require type 4 pili, the type 3 secretion system (T3SS and a flagellum, although flagellum-deficient bacteria can occasionally invade the basal compartment from wounded areas. In the basal compartment, the bacteria inject the T3SS toxins into host cells, disrupting the cytoskeleton and focal contacts to allow their progression under the cells. Thus, P. aeruginosa exploits intrinsic host cell processes to breach the epithelium and invade the subcellular compartment.

  14. Loss of ELF3 immunoexpression is useful for detecting oral squamous cell carcinoma but not for distinguishing between grades of epithelial dysplasia.

    Science.gov (United States)

    AbdulMajeed, Ahmad A; Dalley, Andrew J; Farah, Camile S

    2013-08-01

    Early diagnosis and targeted therapy are crucial to mitigating the morbidity and mortality of oral squamous cell carcinoma. Among the potentially malignant oral disorders, epithelial dysplasia has known association with malignant transformation, but defensible gradation of dysplasia severity presents unmet challenges. Published microarray data has denoted dysregulation of CLSP, ELF3, IFI44, USP18, and CXCL13 genes in potentially malignant oral disorders. The present study investigated the diagnostic potential of these gene products to grade oral epithelial dysplasia severity. Archived biopsies from independent patient cohorts comprised "training" (n=107) and "test" (n=278) sample sets. Immunoreactivity for candidate markers was determined in the "training" set of normal oral mucosa (NOM), mild dysplasia (MD), moderate to severe dysplasia, and oral squamous cell carcinoma (OSCC). The diagnostic potential of ELF3 immunoscoring to improve detection and severity gradation of epithelial dysplasia was assessed with the "test" set. A reciprocal relationship between disease severity and immunoreactivity score for CLSP and ELF3 was observed (MD/NOM to OSCC: Poral lesion severity. Loss of ELF3 immunostaining discriminated OSCC from dysplasia but was unreliable for grading dysplasia severity.

  15. Transformation analysis of oral epithelial dysplasia to carcinoma in-situ and squamous cell carcinoma by p53 expression and gene mutations

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    Mei Syafriadi

    2009-06-01

    Full Text Available Background: It is known that oral squamous epithelial dysplasia (SED and carcinoma in-situ (CIS are precancerous lesion and it could transform to squamous cell carcinoma (SCC. We had reported p53-Protein Over-Expression and Gene Mutational of Oral CIS, such as basaloid, verrucous, and acanthothic/atrophic types, but demarcated between SED to CIS and CIS to SCC and how their transformation is still unclear. It is considered that their molecular behavior related one another. Purpose: To understand the molecular behavior of them we examined p53 exon 5-8 gene mutation and their protein expression in the sequential cases. Methods: Using 10 cases formalin–fixed paraffin sections that composed SED appearance, CIS and SCC in the same case were subjected to P53 immunohistochemistry. Then all cases were subjected to p53 gene mutations analysis. By laser capturing microdissection dysplasia part, CIS part and SCC part were cutted, and followed by direct sequencing of PCR product for exon 5-8. Result: SED p53-protein over-expression in some cells, and the expression was increased to CIS and SCC. Mutational analysis for p53 gene showed that 60% of p53 gene mutation in CIS also found in SCC, therefore SCC had additional mutation in other exon of p53 gene. While no particular mutations were found in SED part of all cases. Conclusion: Carcinoma in-situ is a squamous cell carcinoma eventhough not invasive yet, but squamous epithelial dysplasia is an early step to malignancy. It needs other genes examination to know any genes are involved in the precancerous to cancer transformation process.

  16. Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

    Science.gov (United States)

    Kikuchi, Kentaro; Noguchi, Yoshihiro; de Rivera, Michelle Wendoline Garcia-Niño; Hoshino, Miyako; Sakashita, Hideaki; Yamada, Tsutomu; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; González-López, Blanca Silvia; Ide, Fumio; Kusama, Kaoru

    2016-03-01

    A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

  17. Claudin-5 is restricted to the tight junction region of uterine epithelial cells in the uterus of pregnant/gravid squamate reptiles.

    Science.gov (United States)

    Biazik, Joanna M; Thompson, Michael B; Murphy, Christopher R

    2008-05-01

    Claudin-5, a tight junctional protein associated with ion and size selectivity, has been found in the uterus of skinks. This study has generated critical information about the molecular assembly of the tight junction at various stages of the reproductive cycle in the skink uterus. Recent studies looking at tight junctional proteins found occludin expression in the tight junction region of uterine epithelial cells in the skink uterus; however, occludin did not disclose any further information about the ions and size of ions permeating across the paracellular pathway. A approximately 22-kDa claudin-5 band was detected in the uterus of the skinks present in this study and immunohistochemistry revealed that claudin-5 redistributes to the tight junction region of the lateral plasma membrane of uterine epithelial cells in late stage pregnancy/gravidity. This finding indicates that the tight junction becomes more assembled to precisely regulate ion and solute permeation in late stage pregnancy/gravidity. Claudin-5 with its functional role as a molecular sieve due to the formation of ion and size selective pores suggests that permeation of ions smaller than 0.8 kDa are restricted when claudin-5 is redistributed to the tight junction region of the later plasma membrane. This report is the first description of the molecular mechanisms that may be involved in regulating nutrient provision in the reptilian uterus.

  18. Tight junction changes in epithelial cells by Campylobacter jejuni and non-jejuni Campylobacter species

    DEFF Research Database (Denmark)

    Bücker, Roland; Nielsen, Hans Linde; Krüg, S

    in Ussing chambers. Tight junction (TJ) protein expression was determined by Western blotting, and subcellular TJ distribution was analyzed by confocal laser-scanning microscopy. Apoptosis induction was examined by TUNEL-staining and Western blot of caspase-3 activation. All strains invaded confluent HT-29...

  19. Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

    Directory of Open Access Journals (Sweden)

    Neves-dos-Santos Sandra

    2010-01-01

    Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

  20. Lecithin-Bound Iodine Prevents Disruption of Tight Junctions of Retinal Pigment Epithelial Cells under Hypoxic Stress

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    Masahiko Sugimoto

    2016-01-01

    Full Text Available Aim. We investigated whether lecithin-bound iodine (LBI can protect the integrity of tight junctions of retinal pigment epithelial cells from hypoxia. Method. Cultured human retinal pigment epithelial (ARPE-19 cells were pretreated with LBI. To mimic hypoxic conditions, cells were incubated with CoCl2. We compared the integrity of the tight junctions (TJs of control to cells with either LBI alone, CoCl2 alone, or LBI + CoCl2. The levels of cytokines in the conditioned media were also determined. Results. Significant decrease in the zonula occludens-1 (ZO-1 intensity in the CoCl2 group compared to the control (5787.7 ± 4126.4 in CoCl2 group versus 29244.6 ± 2981.2 in control; average ± standard deviation. But the decrease was not significant in the LBI + CoCl2 (27189.0 ± 11231.1. The levels of monocyte chemoattractant protein-1 (MCP-1 and Chemokine (C-C Motif Ligand 11 (CCL-11 were significantly higher in the CoCl2 than in the control (340.8 ± 43.3 versus 279.7 ± 68.3 pg/mL for MCP-1, and 15.2 ± 12.9 versus 12.5 ± 6.1 pg/mL for CCL-11. With LBI pretreatment, the levels of both cytokines were decreased to 182.6 ± 23.8 (MCP-1 and 5.46 ± 1.9 pg/mL for CCL-11. Blockade of MCP-1 or CCL-11 also shows similar result representing TJ protection from hypoxic stress. Conclusions. LBI results in a protective action from hypoxia.

  1. Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction

    NARCIS (Netherlands)

    Cohen, Daniel J.; Gloerich, Martijn; Nelson, W. James

    2016-01-01

    Epithelial monolayers undergo self-healing when wounded. During healing, cells collectively migrate into the wound site, and the converging tissue fronts collide and form a stable interface. To heal, migrating tissues must form cell-cell adhesions and reorganize from the front-rear polarity characte

  2. The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction.

    Science.gov (United States)

    Ronaghan, Natalie J; Shang, Judie; Iablokov, Vadim; Zaheer, Raza; Colarusso, Pina; Dion, Sébastien; Désilets, Antoine; Leduc, Richard; Turner, Jerrold R; MacNaughton, Wallace K

    2016-09-01

    Barrier dysfunction is a characteristic of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Understanding how the tight junction is modified to maintain barrier function may provide avenues for treatment of IBD. We have previously shown that the apical addition of serine proteases to intestinal epithelial cell lines causes a rapid and sustained increase in transepithelial electrical resistance (TER), but the mechanisms are unknown. We hypothesized that serine proteases increase barrier function through trafficking and insertion of tight junction proteins into the membrane, and this could enhance recovery of a disrupted monolayer after calcium switch or cytokine treatment. In the canine epithelial cell line, SCBN, we showed that matriptase, an endogenous serine protease, could potently increase TER. Using detergent solubility-based cell fractionation, we found that neither trypsin nor matriptase treatment changed levels of tight junction proteins at the membrane. In a fast calcium switch assay, serine proteases did not enhance the rate of recovery of the junction. In addition, serine proteases could not reverse barrier disruption induced by IFNγ and TNFα. We knocked down occludin in our cells using siRNA and found this prevented the serine protease-induced increase in TER. Using fluorescence recovery after photobleaching (FRAP), we found serine proteases induce a greater mobile fraction of occludin in the membrane. These data suggest that a functional tight junction is needed for serine proteases to have an effect on TER, and that occludin is a crucial tight junction protein in this mechanism.

  3. Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway.

    Science.gov (United States)

    Sivagurunathan, Suganya; Palanisamy, Karthikka; Arunachalam, Jayamuruga Pandian; Chidambaram, Subbulakshmi

    2017-03-01

    PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.

  4. The epithelial membrane protein 1 is a novel tight junction protein of the blood-brain barrier.

    Science.gov (United States)

    Bangsow, Thorsten; Baumann, Ewa; Bangsow, Carmen; Jaeger, Martina H; Pelzer, Bernhard; Gruhn, Petra; Wolf, Sabine; von Melchner, Harald; Stanimirovic, Danica B

    2008-06-01

    In the central nervous system, a constant microenvironment required for neuronal cell activity is maintained by the blood-brain barrier (BBB). The BBB is formed by the brain microvascular endothelial cells (BMEC), which are sealed by tight junctions (TJ). To identify genes that are differentially expressed in BMEC compared with peripheral endothelial cells, we constructed a subtractive cDNA library from porcine BMEC (pBMEC) and aortic endothelial cells (AOEC). Screening the library for differentially expressed genes yielded 26 BMEC-specific transcripts, such as solute carrier family 35 member F2 (SLC35F2), ADP-ribosylation factor-like 5B (ARL5B), TSC22 domain family member 1 (TSC22D1), integral membrane protein 2A (ITM2A), and epithelial membrane protein 1 (EMP1). In this study, we show that EMP1 transcript is enriched in pBMEC compared with brain tissue and that EMP1 protein colocalizes with the TJ protein occludin in mouse BMEC by coimmunoprecipitation and in rat brain vessels by immunohistochemistry. Epithelial membrane protein 1 expression was transiently induced in laser-capture microdissected rat brain vessels after a 20-min global cerebral ischemia, in parallel with the loss of occludin immunoreactivity. The study identifies EMP1 as a novel TJ-associated protein of the BBB and suggests its potential role in the regulation of the BBB function in cerebral ischemia.

  5. Evidence for epithelial-mesenchymal transition in cancer stem cells of head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Chao Chen

    Full Text Available Initiation, growth, recurrence, and metastasis of head and neck squamous cell carcinomas (HNSCC have been related to the behavior of cancer stem cells (CSC that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH1 activity. We quantified and enriched ALDH1(+ cells within HNSCC cell lines and subsequently characterized their phenotypical and functional properties like invasion capacity and epithelial-mesenchymal transition (EMT. Spheroid culture enriched CSC from five HNSCC cell lines by up to 5-fold. In spheroid-derived cells (SDC and the parental monolayer-derived cell line ALDH1, CD44, CD24, E-Cadherin, α-SMA, and Vimentin expression was compared by flow-cytometry and immunofluorescence together with proliferation and cell cycle analysis. Invasion activity was evaluated by Matrigel assay and expression of stemness-related transcription factors (TF Nanog, Oct3/4, Sox2 and EMT-related genes Snail1 and 2, and Twist by real-time PCR. All cell lines formed spheroids that could self-renew and be serially re-passaged. ALDH1 expression was significantly higher in SDC. ALDH1(+ cells showed increased colony-formation. The proportion of cells with a putative CSC marker constellation of CD44(+/CD24(- was highly variable (0.5% to 96% in monolayer and spheroid cultures and overlapped in 0%-33% with the CD44(+/CD24(-/ALDH1(+ cell subset. SDC had significantly higher invading activity. mRNA of the stemness-related genes Sox2, Nanog, and Oct3/4 was significantly increased in SDC of all cell lines. Twist was significantly increased in two while Snail2 showed a significant increase in one and a significant decrease in SDC of two cell lines. SDC had a higher G0 phase proportion, showed high-level expression of α-SMA and Vimentin, but significantly decreased E-Cadherin expression. HNSCC-lines harbor potential CSC, characterized by ALDH1 and stemness marker TF expression as well as properties like invasiveness, quiescence, and EMT. CSC can be

  6. Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal squamous cancer cells.

    Science.gov (United States)

    Wang, Yan-Yang; Yang, Yin-Xue; Zhao, Ren; Pan, Shu-Ting; Zhe, Hong; He, Zhi-Xu; Duan, Wei; Zhang, Xueji; Yang, Tianxin; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2015-01-01

    Natural and synthetic triterpenoids have been shown to kill cancer cells via multiple mechanisms. The therapeutic effect and underlying mechanism of the synthetic triterpenoid bardoxolone methyl (C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; CDDO-Me) on esophageal cancer are unclear. Herein, we aimed to investigate the anticancer effects and underlying mechanisms of CDDO-Me in human esophageal squamous cell carcinoma (ESCC) cells. Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G2/M phase, and induced apoptosis in human ESCC Ec109 and KYSE70 cells. The G2/M arrest was accompanied with upregulated p21Waf1/Cip1 and p53 expression. CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl), B-cell lymphoma 2 (Bcl-2), cleaved caspase-9, and cleaved poly ADP ribose polymerase (PARP) levels but increased the expression level of Bcl-2-associated X (Bax). Furthermore, CDDO-Me induced autophagy in both Ec109 and KYSE70 cells via suppression of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. There were interactions between the autophagic and apoptotic pathways in Ec109 and KYSE70 cells subject to CDDO-Me treatment. CDDO-Me also scavenged reactive oxygen species through activation of the nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) pathway in Ec109 and KYSE70 cells. CDDO-Me inhibited cell invasion, epithelial-mesenchymal transition, and stemness in Ec109 and KYSE70 cells. CDDO-Me significantly downregulated E-cadherin but upregulated Snail, Slug, and zinc finger E-box-binding homeobox 1 (TCF-8/ZEB1) in Ec109 and KYSE70 cells. CDDO-Me significantly decreased the expression of octamer-4, sex determining region Y-box 2 (Sox-2), Nanog, and B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), all markers of cancer cell stemness, in Ec109 and KYSE70 cells. Taken together, these results indicate that CDDO-Me is a promising anticancer agent

  7. Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Wang, Li; Xing, Jie; Cheng, Rui; Shao, Ying; Li, Peng; Zhu, Shengtao; Zhang, Shutian

    2015-01-01

    Esophageal cancer is one of the most common malignant cancers worldwide. The molecular mechanism of esophageal squamous cell carcinoma (ESCC) is still poorly understood. ESE3 is a member of the Ets transcription family, which is only expressed in epithelial tissues and acts as a tumor suppressor gene in prostate cancer. Our study aim was to confirm whether ESE3 is involved in the carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC tissues. Immunofluorescence and western blot analyses of the normal esophageal cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells showed restoration of the nuclear localization of ESE3. EC9706 cells with re-localization of ESE3 to the nucleus showed inhibition of proliferation, colony formation, migration, and invasion. To explore the possible mechanism of the differences in localization of ESE3 in normal esophageal cells and ESCC cells, ESCC cell lines were treated with the nuclear export inhibitor leptomycin B, transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen according to the well-known mechanisms of protein translocation. However, the localization of ESE3 was unchanged after these treatments. The sequence of ESE3 cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI Genebank database, indicating that there was no mutation in the coding region of ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important role in the carcinogenesis of ESCC through changes in subcellular localization and may act as a tumor suppressor gene in ESCC, although the mechanisms require further study.

  8. Abnormal Localization and Tumor Suppressor Function of Epithelial Tissue-Specific Transcription Factor ESE3 in Esophageal Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available Esophageal cancer is one of the most common malignant cancers worldwide. The molecular mechanism of esophageal squamous cell carcinoma (ESCC is still poorly understood. ESE3 is a member of the Ets transcription family, which is only expressed in epithelial tissues and acts as a tumor suppressor gene in prostate cancer. Our study aim was to confirm whether ESE3 is involved in the carcinogenesis of ESCC. Immunohistochemical analysis revealed that ESE3 was mainly located in cell nuclei of normal tissues and the cytoplasm in ESCC tissues. Immunofluorescence and western blot analyses of the normal esophageal cell line HEEpiC and ESCC cell lines EC9706 TE-1, KYSE150, and KYSE410 confirmed these results. pEGFP-ESE3 and pcDNA3.1-V5/HisA-ESE3 plasmids were constructed for overexpression of ESE3 in EC9706 and KYSE150 cells. The stably transfected cells showed restoration of the nuclear localization of ESE3. EC9706 cells with re-localization of ESE3 to the nucleus showed inhibition of proliferation, colony formation, migration, and invasion. To explore the possible mechanism of the differences in localization of ESE3 in normal esophageal cells and ESCC cells, ESCC cell lines were treated with the nuclear export inhibitor leptomycin B, transcription inhibitor actinomycin D, PKC inhibitor sphinganine, P38 MAPK inhibitor SB202190, and CK II inhibitor TBCA. These reagents were chosen according to the well-known mechanisms of protein translocation. However, the localization of ESE3 was unchanged after these treatments. The sequence of ESE3 cDNA in ESCC cells was identical to the standard sequence of ESE3 in the NCBI Genebank database, indicating that there was no mutation in the coding region of ESE3 in ESCC. Taken together, our study suggests that ESE3 plays an important role in the carcinogenesis of ESCC through changes in subcellular localization and may act as a tumor suppressor gene in ESCC, although the mechanisms require further study.

  9. Effects of H pylori infection on gap-junctional intercellular communication and proliferation of gastric epithelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To explore the effects of H pylori infection on gap-junctional intercellular communication (GJIC) and proliferation of gastric epithelial cells in vitro. METHODS: A human gastric epithelial cell line (SGC-7901) cultured on coverslips was exposed overnight to intact H pylori (CagA+ or CagA- strains) and sonicated extracts, respectively. GJIC between the cells was detected by fluorescence redistribution after photobleaching (FRAP) technique. Proliferation of SGC cells was determined by methylthiazolyl tetrazolium (MTT)assay.RESULTS: When compared with control in which cells were cultured with simple medium alone, both CagA+ and CagA- H pylori isolates could inhibit GJIC (CagA+:F = 57.98, P < 0.01; CagA-: F = 29.59, P < 0.01) and proliferation (CagA+: F = 42.65, P < 0.01; CagA-: F =58.14, P < 0.01) of SGC-7901 cells. Compared with CagA- strains, CagA+ H pylori more significantly downregulated GJIC of gastric cells (intact H pylori: t = 13.86,P < 0.01; sonicated extracts: t = 11.87, P < 0.01) and inhibited proliferation gastric cells to a lesser extent in vitro (intact H pylori: t = 3.06, P < 0.05; sonicated extracts: t = 3.94, P < 0.01).CONCLUSION: Compared with CagA- H pylori strains,CagA+ strains down-regulate GJIC of gastric epithelial cells more significantly and inhibit proliferation of gastric cells to a lesser extent in vitro. H pylori, especially CagA+ strains, may play an important role in gastric carcinogenesis.

  10. β-catenin expression in areca quid chewing-associated oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells.

    Science.gov (United States)

    Lee, Shiuan-Shinn; Tsai, Chung-Hung; Tsai, Lo-Lin; Chou, Ming-Chih; Chou, Ming-Yung; Chang, Yu-Chao

    2012-04-01

    Nuclear localization of β-catenin is known to associate with malignant transformation of many squamous cell carcinomas. The aim of this study was to compare β-catenin expression in normal human oral epithelium and areca quid chewing associated oral squamous cell carcinomas (OSCCs) and further to explore the potential mechanisms that may lead to induce β-catenin expression. A total of 40 areca quid chewing-associated OSCCs and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, extracellular signal-regulated protein kinase inhibitor PD98059, glutathione precursor N-acetyl-l-cysteine (NAC), tyrosine kinase inhibitor herbimycin-A, p38 inhibitor SB203580, and phosphatidylinositaol 3-kinase inhibitor LY294002 were added to find the possible regulatory mechanisms. β-catenin expression was significantly higher in OSCC specimens than that in normal oral epithelial specimens (p Arecoline was found to elevate β-catenin expression in a dose-dependent manner (p arecoline-induced β-catenin expression (p arecoline is downregulated by PD98059, NAC, herbimycin-A, SB203580, and LY294002. Copyright © 2012. Published by Elsevier B.V.

  11. Significance and prognostic value of lysosomal enzyme activities measured in surgically operated adenocarcinomas of the gastroesophageal junction and squamous cell carcinomas of the lower third of esophagus

    Institute of Scientific and Technical Information of China (English)

    Aron Altorjay; Balazs Paal; Nicolette Sohar; Janos Kiss; Imre Szanto; Istvan Sohar

    2005-01-01

    AIM: To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction (GEJ) and the squamous cell carcinomas of the lower third of the esophagus (LTE).METHODS: Between February 1, 1997 and February 1,2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients' samples (81%). Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ (n = 8), type Ⅱ (n = 12), type Ⅲ (n = 9), and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient.These data were further analyzed to establish the correlation with tumor localization, TNM stage (lymph-node involvement), histological type (papillary, signet-ring cell,tubular), state of differentiation (good, moderate, poor),and survival (≤24 or ≥24 mo).RESULTS: In adenocarcinomas, the activity of α-mannosidase (AMAN), cathepsin B (CB) and dipeptidyl-peptidase Ⅰ (DPP Ⅰ) increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase I in addition to these three. There was a statistical correlation of AMAN,CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical intervention were

  12. JAM-A and aPKC: A close pair during cell-cell contact maturation and tight junction formation in epithelial cells.

    Science.gov (United States)

    Ebnet, Klaus

    2013-01-01

    Cell-cell adhesion plays a critical role in the formation of barrier-forming epithelia. The molecules which mediate cell-cell adhesion frequently act as signaling molecules by recruiting and/or assembling cytoplasmic protein complexes. Junctional Adhesion Molecule (JAM)-A interacts with the cell polarity protein PAR-3, a member of the PAR-3-aPKC-PAR-6 complex, which regulates the formation of cell-cell contacts and the development of tight junctions (TJs). In our recent study we found that JAM-A is localized at primordial, spot-like cell-cell junctions (pAJs) in a non-phosphorylated form. After the recruitment of the PAR-aPKC complex and its activation at pAJs, aPKC phosphorylates JAM-A at Ser285 to promote the maturation of immature junctions. In polarized epithelial cells, aPKC phosphorylates JAM-A selectively at the TJs to maintain the barrier function of TJs. Thus, through mutual regulation, JAM-A and aPKC form a functional unit that regulates the establishment of barrier-forming junctions in vertebrate epithelial cells.

  13. Involvement of YAP, TAZ and HSP90 in contact guidance and intercellular junction formation in corneal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Vijay Krishna Raghunathan

    Full Text Available The extracellular environment possesses a rich milieu of biophysical and biochemical signaling cues that are simultaneously integrated by cells and influence cellular phenotype. Yes-associated protein (YAP and transcriptional co-activator with PDZ-binding motif (WWTR1; TAZ, two important signaling molecules of the Hippo pathway, have been recently implicated as nuclear relays of cytoskeletal changes mediated by substratum rigidity and topography. These proteins intersect with other important intracellular signaling pathways (e.g. Wnt and TGFβ. In the cornea, epithelial cells adhere to the stroma through a 3-dimensional topography-rich basement membrane, with features in the nano-submicron size-scale that are capable of profoundly modulating a wide range of fundamental cell behaviors. The influences of substratum-topography, YAP/TAZ knockdown, and HSP90 inhibition on cell morphology, YAP/TAZ localization, and the expression of TGFβ2 and CTGF, were investigated. The results demonstrate (a that knockdown of TAZ enhances contact guidance in a YAP dependent manner, (b that CTGF is predominantly regulated by YAP and not TAZ, and (c that TGFβ2 is regulated by both YAP and TAZ in these cells. Additionally, inhibition of HSP90 resulted in nuclear localization and subsequent transcriptional-activation of YAP, formation of cell-cell junctions and co-localization of E-cadherin and β-catenin at adherens junctions. Results presented in this study reflect the complexities underlying the molecular relationships between the cytoskeleton, growth factors, heat shock proteins, and co-activators of transcription that impact mechanotransduction. The data reveal the importance of YAP/TAZ on the cell behaviors, and gene and protein expression.

  14. The tight junction protein ZO-2 associates with Jun, Fos and C/EBP transcription factors in epithelial cells.

    Science.gov (United States)

    Betanzos, Abigail; Huerta, Miriam; Lopez-Bayghen, Esther; Azuara, Elisa; Amerena, José; González-Mariscal, Lorenza

    2004-01-01

    ZO-2 is a membrane-associated guanylate kinase (MAGUK) protein present at the tight junction (TJ) of epithelial cells. While confluent monolayers have ZO-2 at their cellular borders, sparse cultures conspicuously show ZO-2 at the nuclei. To study the role of nuclear ZO-2, we tested by pull-down assays and gel shift analysis the interaction between ZO-2 GST fusion proteins and different transcription factors. We identified the existence of a specific interaction of ZO-2 with Fos, Jun and C/EBP (CCAAT/enhancer binding protein). To analyze if this association is present "in vivo", we performed immunoprecipitation and immunolocalization experiments, which revealed an interaction of ZO-2 with Jun, Fos and C/EBP not only at the nucleus but also at the TJ region. To test if the association of ZO-2 with AP-1 (activator protein-1) modulates gene transcription, we performed reporter gene assays employing chloramphenicol acetyltransferase (CAT) constructs with promoters under the control of AP-1 sites. We observed that the co-transfected ZO-2 down-regulates CAT expression in a dose-dependent manner. Since ZO-2 is a multidomain protein, we proceeded to determine which region of the molecule is responsible for the modulation of gene expression, and observed that both the amino and the carboxyl domains are capable of inhibiting gene transcription.

  15. Comparison of destructive periodontal disease in blue iris mink to PCB 126-induced mandibular and maxillary squamous epithelial proliferation in natural dark mink.

    Science.gov (United States)

    Ellick, Rachel M; Fitzgerald, Scott D; Link, Jane E; Bursian, Steven J

    2013-01-01

    Mink (Mustela vison) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like chemicals have been reported to develop mandibular and maxillary squamous cell proliferation that results in the destruction of alveolar bone and eventual tooth loss. This jaw lesion has been reported in wild mink collected from areas contaminated with TCDD-like compounds and is a potential biomarker for exposure to these chemicals. The blue iris strain of domestic mink is prone to develop severe periodontal disease, which results in destruction of bone and tooth loss that is grossly similar to the lesion induced by exposure to TCDD-like chemicals. A histological assessment of jaws from blue iris mink and natural dark mink exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) was done to determine whether the oral lesions are similar. The jaw tissue from the blue iris mink had lesions indicative of lymphoplasmacytic gingivitis and osteomyelitis, caused by inflammation entering the dental sulcus, while the jaw tissue from the mink exposed to PCB 126 exhibited squamous epithelial proliferation. Therefore, it was determined that the tooth loss and bone destruction seen in these mink are of different origin despite the similarity of the gross clinical signs.

  16. Outcomes of oral squamous cell carcinoma arising from oral epithelial dysplasia: rationale for monitoring premalignant oral lesions in a multidisciplinary clinic.

    Science.gov (United States)

    Ho, M W; Field, E A; Field, J K; Risk, J M; Rajlawat, B P; Rogers, S N; Steele, J C; Triantafyllou, A; Woolgar, J A; Lowe, D; Shaw, R J

    2013-10-01

    Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.

  17. Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial-mesenchymal transition.

    Science.gov (United States)

    Zhang, Chun-Yang; Li, Ren-Ke; Qi, Yu; Li, Xiang-Nan; Yang, Yang; Liu, Dong-Lei; Zhao, Jia; Zhu, Deng-Yan; Wu, Kai; Zhou, Xu-Dong; Zhao, Song

    2016-10-01

    Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC. Overexpression of SPRY4-IT1 can increase in vitro motility of ESCC cells via induction of epithelial-mesenchymal transition (EMT), which is characterized by increasing the expression of vimentin (Vim) and fibronectin (FN) with a concomitant decrease of E-cadherin (E-Cad) and ZO-1, while silencing of SPRY4-IT1 significantly inhibits the in vitro motility of ESCC cells. Further, the knockdown of SPRY4-IT1 also significantly attenuates TFG-β-induced EMT of ESCC cells. Further, lncRNA SPRY4-IT1 can directly increase the transcription, expression, and nuclear localization of Snail, one key transcription factor during the EMT processes of cancer cells, while siRNA-mediated specific knockdown of Snail can significantly attenuate SPRY4-IT1-induced EMT of ESCC cells. Our results suggest that lncRNA SPRY4-IT1 might be considered as a novel oncogene involved in ESCC progression.

  18. miR-200b inhibits TNF-α-induced IL-8 secretion and tight junction disruption of intestinal epithelial cells in vitro.

    Science.gov (United States)

    Shen, Yujie; Zhou, Min; Yan, Junkai; Gong, Zizhen; Xiao, Yongtao; Zhang, Cong; Du, Peng; Chen, Yingwei

    2017-02-01

    Inflammatory bowel diseases (IBDs) are chronic, inflammatory disorders of the gastrointestinal tract with unclear etiologies. Intestinal epithelial cells (IECs), containing crypt and villus enterocytes, occupy a critical position in the pathogenesis of IBDs and are a major producer of immunoregulatory cytokines and a key component of the intact epithelial barrier. Previously, we have reported that miR-200b is involved in the progression of IBDs and might maintain the integrity of the intestinal epithelial barrier via reducing the loss of enterocytes. In this study, we further investigated the impact of miR-200b on intestinal epithelial inflammation and tight junctions in two distinct differentiated states of Caco-2 cells after TNF-α treatment. We demonstrated that TNF-α-enhanced IL-8 expression was decreased by microRNA (miR)-200b in undifferentiated IECs. Simultaneously, miR-200b could alleviate TNF-α-induced tight junction (TJ) disruption in well-differentiated IECs by reducing the reduction in the transepithelial electrical resistance (TEER), inhibiting the increase in paracellular permeability, and preventing the morphological redistribution of the TJ proteins claudin 1 and ZO-1. The expression levels of the JNK/c-Jun/AP-1 and myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) pathways were attenuated in undifferentiated and differentiated enterocytes, respectively. Furthermore, a dual-luciferase reporter gene detection system provided direct evidence that c-Jun and MLCK were the specific targets of miR-200b. Collectively, our results highlighted that miR-200b played a positive role in IECs via suppressing intestinal epithelial IL-8 secretion and attenuating TJ damage in vitro, which suggested that miR-200b might be a promising strategy for IBD therapy.

  19. Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.

    Science.gov (United States)

    Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Ito, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

    2011-10-01

    The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The inhibition of COPII trafficking is important for intestinal epithelial tight junction disruption during enteropathogenic Escherichia coli and Citrobacter rodentium infection.

    Science.gov (United States)

    Thanabalasuriar, Ajitha; Kim, Jinoh; Gruenheid, Samantha

    2013-01-01

    Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are bacterial pathogens that cause severe illnesses in humans. Citrobacter rodentium is a related mouse pathogen that serves as a small animal model for EPEC and EHEC infections. EPEC, EHEC and C. rodentium translocate bacterial virulence proteins directly into host intestinal cells via a type III secretion system (T3SS). Non-LEE-encoded effector A (NleA) is a T3SS effector that is common to EPEC, EHEC and C. rodentium. NleA interacts with and inhibits the mammalian COPII complex, impairing cellular secretion; this interaction is required for bacterial virulence. Although diarrhea is a hallmark of EPEC, EHEC and C. rodentium infections, the underlying mechanisms are not well characterized. One of the essential functions of the intestine is to maintain a barrier between the lumen and submucosa. Tight junctions seal the space between adjacent epithelial cells creating this barrier. Consequently, it is thought that the disruption of intestinal epithelial tight junctions by EPEC, EHEC, and C. rodentium could result in a loss of barrier function. In this study, we demonstrate that NleA mediated COPII inhibition is required for EPEC- and C. rodentium-mediated disruption of tight junction proteins and increases in fecal water content.

  1. Single cell migration in oral squamous cell carcinoma - possible evidence of epithelial-mesenchymal transition in vivo

    DEFF Research Database (Denmark)

    Jensen, David H; Reibel, Jesper; Mackenzie, Ian C

    2015-01-01

    BACKGROUND: The invasion of cancer cells into the surrounding normal tissue is one of the defining features of cancer. While the phenomena of tumour budding, epithelial-mesenchymal transition and the presence of myofibroblasts have independently been shown to be related to a poor prognosis of ora...

  2. Neuropilin-1 promotes epithelial-to-mesenchymal transition by stimulating nuclear factor-kappa B and is associated with poor prognosis in human oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Weiming Chu

    Full Text Available The epithelial-to-mesenchymal transition (EMT is a key process in carcinogenesis, invasion, and metastasis of oral squamous cell carcinoma (OSCC. In our previous studies, we found that neuropilin-1 (NRP1 is overexpressed in tongue squamous cell carcinoma and that this overexpression is associated with cell migration and invasion. Nuclear factor-kappa B (NF-κB plays an essential role both in the induction and the maintenance of EMT and tumor metastasis. Therefore, we hypothesized that NRP1 induces EMT, and that NRP1-induced migration and invasion may be an important mechanism for promoting invasion and metastasis of OSCC through NF-κB activation.The variations in gene and protein expression and the changes in the biological behavior of OSCC cell lines transfected with a vector encoding NRP1, or the corresponding vector control, were evaluated. NRP1 overexpression promoted EMT and was associated with enhanced invasive and metastatic properties. Furthermore, the induction of EMT promoted the acquisition of some cancer stem cell (CSC-like characteristics in OSCC cells. We addressed whether selective inhibition of NF-κB suppresses the NRP1-mediated EMT by treating cells with pyrrolidinedithiocarbamate ammonium (PDTC, an inhibitor of NF-κB. Immunohistochemical analysis of NRP1 in OSCC tissue samples further supported a key mediator role for NRP1 in tumor progression, lymph node metastasis, and indicated that NRP1 is a predictor for poor prognosis in OSCC patients.Our results indicate that NRP1 may regulate the EMT process in OSCC cell lines through NF-κB activation, and that higher NRP1 expression levels are associated with lymph node metastasis and poor prognosis in OSCC patients. Further investigation of the role of NRP1 in tumorigenesis may help identify novel targets for the prevention and therapy of oral cancers.

  3. Effects of ethanol and acetaldehyde on tight junction integrity: in vitro study in a three dimensional intestinal epithelial cell culture model.

    Directory of Open Access Journals (Sweden)

    Elhaseen Elamin

    Full Text Available BACKGROUND: Intestinal barrier dysfunction and translocation of endotoxins are involved in the pathogenesis of alcoholic liver disease. Exposure to ethanol and its metabolite, acetaldehyde at relatively high concentrations have been shown to disrupt intestinal epithelial tight junctions in the conventional two dimensional cell culture models. The present study investigated quantitatively and qualitatively the effects of ethanol at concentrations detected in the blood after moderate ethanol consumption, of its metabolite acetaldehyde and of the combination of both compounds on intestinal barrier function in a three-dimensional cell culture model. METHODS AND FINDINGS: Caco-2 cells were grown in a basement membrane matrix (Matrigel™ to induce spheroid formation and were then exposed to the compounds at the basolateral side. Morphological differentiation of the spheroids was assessed by immunocytochemistry and transmission electron microscopy. The barrier function was assessed by the flux of FITC-labeled dextran from the basal side into the spheroids' luminal compartment using confocal microscopy. Caco-2 cells grown on Matrigel assembled into fully differentiated and polarized spheroids with a central lumen, closely resembling enterocytes in vivo and provide an excellent model to study epithelial barrier functionality. Exposure to ethanol (10-40 mM or acetaldehyde (25-200 µM for 3 h, dose-dependently and additively increased the paracellular permeability and induced redistribution of ZO-1 and occludin without affecting cell viability or tight junction-encoding gene expression. Furthermore, ethanol and acetaldehyde induced lysine residue and microtubules hyperacetylation. CONCLUSIONS: These results indicate that ethanol at concentrations found in the blood after moderate drinking and acetaldehyde, alone and in combination, can increase the intestinal epithelial permeability. The data also point to the involvement of protein hyperacetylation in

  4. Cancer stem cell, cytokeratins and epithelial to mesenchymal transition markers expression in oral squamous cell carcinoma derived from ortothopic xenoimplantation of CD44(high) cells.

    Science.gov (United States)

    de Andrade, Nathália Paiva; Rodrigues, Maria Fernanda Setúbal Destro; Rodini, Camila Oliveira; Nunes, Fabio Daumas

    2017-03-01

    Oral squamous cell carcinoma (OSCC) is the most prevalent neoplasia of oral cavity worldwide and prognosis remains unchanged in decades. Recently, different authors reported that head and neck squamous cell carcinomas have a subpopulation of tumor initiating cells that apparently correspond to cancer stem cells (CSC) and are also responsible for tumor growth and metastasis. The purpose of the present study was to investigate the microscopic and phenotypic characteristics of OSCC tumors induced after orthotopic xenoimplantation of SCC9(WT) cell line and CSC-enriched subpopulation isolated from SCC9 cell line based on high expression of the putative CSC marker CD44. Different numbers of FACS-sorted SCC9 CD44(high) and CD44(low) cells as well as SCC9(WT) (wild type) were transplanted into the tongue of BALB/C nude (NOD/SCID) mice to evaluate their tumorigenic potential. Sixty days post-induction, tumors were morphologically characterized and immunostained for CSC markers (CD44, Nanog and Bmi-1), epithelial-mesenchymal transition (Snail, Slug) and epithelial differentiating cell markers (cytokeratins 4, 13, 15, 17 and 19), as well as E-cadherin and β-catenin. The data presented here shows that SCC9 CD44(high) cells have higher ability to form tumors than SCC9 CD44(low) cells, even when significantly lower numbers of SCC9 CD44(high) cells were transplanted. Immunoassessment of tumors derived from SCC9 CD44(high) cells revealed high expression of cytokeratin CK19, β-catenin, E-cadherin and CD44, and negative or low expression of CK17, CK4, CK15, CK13, Nanog, Bmi-1, Snail and Slug. While tumors derived from SCC9(WT) showed high expression of CK17, CK19, CD44, Nanog, Bmi-1, Snail and Slug, and negative or low expression of CK4, CK15, CK13, β-catenin and E-cadherin. Thus, SCC9 CD44(high) cells were highly tumorigenic, capable of originating heterogeneous tumors and these tumors have a immunohistochemical profile different from those formed by the wild type cell line

  5. 'Special K' and a Loss of Cell-To-Cell Adhesion in Proximal Tubule-Derived Epithelial Cells: Modulation of the Adherens Junction Complex by Ketamine

    Science.gov (United States)

    Hills, Claire E.; Jin, Tianrong; Siamantouras, Eleftherios; Liu, Issac K-K; Jefferson, Kieran P.; Squires, Paul E.

    2013-01-01

    Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. PMID:24009666

  6. Long Non Coding RNA MALAT1 Promotes Tumor Growth and Metastasis by inducing Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Zhou, Xuan; Liu, Su; Cai, Guoshuai; Kong, Lingping; Zhang, Tingting; Ren, Yu; Wu, Yansheng; Mei, Mei; Zhang, Lun; Wang, Xudong

    2015-11-02

    The prognosis of advanced oral squamous cell carcinoma (OSCC) patients remains dismal, and a better understanding of the underlying mechanisms is critical for identifying effective targets with therapeutic potential to improve the survival of patients with OSCC. This study aims to clarify the clinical and biological significance of metastasis-associated long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. We found that MALAT1 is overexpressed in OSCC tissues compared to normal oral mucosa by real-time PCR. MALAT1 served as a new prognostic factor in OSCC patients. When knockdown by small interfering RNA (siRNA) in OSCC cell lines TSCCA and Tca8113, MALAT1 was shown to be required for maintaining epithelial-mesenchymal transition (EMT) mediated cell migration and invasion. Western blot and immunofluorescence staining showed that MALAT1 knockdown significantly suppressed N-cadherin and Vimentin expression but induced E-cadherin expression in vitro. Meanwhile, both nucleus and cytoplasm levels of β-catenin and NF-κB were attenuated, while elevated MALAT1 level triggered the expression of β-catenin and NF-κB. More importantly, targeting MALAT1 inhibited TSCCA cell-induced xenograft tumor growth in vivo. Therefore, these findings provide mechanistic insight into the role of MALAT1 in regulating OSCC metastasis, suggesting that MALAT1 is an important prognostic factor and therapeutic target for OSCC.

  7. Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells.

    Science.gov (United States)

    Smith, Stephen P; Scarpini, Cinzia G; Groves, Ian J; Odle, Richard I; Coleman, Nicholas

    2016-07-26

    Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of 'master regulators' for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins.

  8. The master switch: Comparative study of mast cell in oral epithelial dysplasia, oral submucous fibrosis and oral squamous cells carcinoma and their association with inflammation and angiogenesis

    Directory of Open Access Journals (Sweden)

    Neethu Telagi

    2015-01-01

    Full Text Available Background: Dental and medical practitioners encounter wide spectrum of oral lesions in their day-to-day practice. Many of the lesions such as leukoplakia, oral submucous fibrosis (OSF, etc., are associated with tobacco and betel nut chewing. Oral leukoplakia, OSF, oral lichen planus and oral squamous cell carcinoma (OSCC are the most commonly occurring oral diseases associated with characteristic clinical and histological features and are associated with chronic inflammation at some stage of the disease process. Aims: To study and compare the number, morphology and topographical distribution of mast cells in oral epithelial dysplasia (OED, OSF and OSCC and to correlate different types of mast cells with the inflammatory infiltrate and vascularity of the lesions. Materials and Methods: Total number of subjects was 120 and equally divided into four groups of 30 as controls, OED, OSF and OSCC cases. Two sections of from each tissue embedded in paraffin wax block were made which were stained with hematoxylin and eosin and toluidine blue stain. Mast cells were counted in five different zones. Results: In the present study, increased numbers of mast cells were seen in all lesions. The cases with mild, moderate and severe inflammation showed increased number of typical (TMCs, atypical (AMCs and granular mast cells (GMCs, respectively. Conclusion: The result of the present study concludes that the mast cells play a key role in mediating the cross links between external angiogenic agent and local immunologic factors.

  9. Knockdown of Snail inhibits epithelial-mesenchymal transition of human laryngeal squamous cell carcinoma Hep-2 cells through VDR signaling pathway.

    Science.gov (United States)

    Zhao, Xue; Yu, Dan; Yang, Jingpu; Xue, Kai; Liu, Yan; Jin, Chunshun

    2017-08-14

    It has been well-documented that Snail plays a decisive role in various tumors. However, the direct effect of Snail on laryngeal squamous cell carcinoma (LSCC) has not been elaborated. In this study, we firstly detected the expression of Snail in 14 samples of patients with LSCC and found that its content was high in cancer tissues compared with adjacent tissues. Then we established LSCC Hep-2 cells with Snail silencing and validated the knockdown efficiency by western blotting and real-time PCR. Results showed that silencing of Snail significantly inhibited the ability of adhesion, migration, and invasion of Hep-2 cells. Further study revealed that knockdown of Snail suppressed the epithelial-mesenchymal transition process of Hep-2 cells, as evidenced by downregulation of matrix metallopeptidase (MMP)-2, MMP-9, integrin subunit beta 1 (ITGβ1), β-catenin, vimentin, N-cadherin, and fibronectin (FN), while upregulation of vitamin D receptor (VDR) and E-cadherin. Additionally, transfection with the small interfering RNA of VDR reversed the effect induced by Snail silencing in Hep-2 cells. Taken together, these results demonstrate that knockdown of Snail can inhibit the EMT process of LSCC cells through VDR signaling pathway in vitro.

  10. Grape seed proanthocyanidins inhibit the invasive potential of head and neck cutaneous squamous cell carcinoma cells by targeting EGFR expression and epithelial-to-mesenchymal transition

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    Sun Qian

    2011-12-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is responsible for over 20,000 deaths every year in United States. Most of the deaths are due, in large part, to its propensity to metastasize. We have examined the effect of bioactive component grape seed proanthocyanidins (GSPs on human cutaneous HNSCC cell invasion and the molecular mechanisms underlying these effects using SCC13 cell line as an in vitro model. Methods The therapeutic effects of GSPs on cancer cell invasion were studied using Boyden chamber and wound healing assays. The effects of GSPs on the levels of various proteins related with cancer cell invasion were determined using western blot analysis. Results Using in vitro cell invasion assays, we observed that treatment of SCC13 cells with GSPs resulted in a concentration-dependent inhibition of cell invasion of these cells, which was associated with a reduction in the levels of epidermal growth factor receptor (EGFR. Treatment of cells with gefitinib and erlotinib, inhibitors of EGFR, or transient transfection of SCC13 cells with EGFR small interfering RNA, also inhibited invasion of these cells. The inhibition of cell invasion by GSPs was associated with the inhibition of the phosphorylation of ERK1/2, a member of mitogen-activated protein kinase family. Treatment of cells with UO126, an inhibitor of MEK, also inhibited the invasion potential of SCC13 cells. Additionally, inhibition of human cutaneous HNSCC cell invasion by GSPs was associated with reversal of epithelial-to-mesenchymal transition (EMT process, which resulted in an increase in the levels of epithelial biomarker (E-cadherin while loss of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin in cells. Similar effect on EMT biomarkers was also observed when cells were treated with erlotinib. Conclusion The results obtained from this study indicate that grape seed proanthocyanidins have the ability to inhibit the invasion of human cutaneous

  11. Grape seed proanthocyanidins inhibit the invasive potential of head and neck cutaneous squamous cell carcinoma cells by targeting EGFR expression and epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Sun, Qian; Prasad, Ram; Rosenthal, Eben; Katiyar, Santosh K

    2011-12-21

    Head and neck squamous cell carcinoma (HNSCC) is responsible for over 20,000 deaths every year in United States. Most of the deaths are due, in large part, to its propensity to metastasize. We have examined the effect of bioactive component grape seed proanthocyanidins (GSPs) on human cutaneous HNSCC cell invasion and the molecular mechanisms underlying these effects using SCC13 cell line as an in vitro model. The therapeutic effects of GSPs on cancer cell invasion were studied using Boyden chamber and wound healing assays. The effects of GSPs on the levels of various proteins related with cancer cell invasion were determined using western blot analysis. Using in vitro cell invasion assays, we observed that treatment of SCC13 cells with GSPs resulted in a concentration-dependent inhibition of cell invasion of these cells, which was associated with a reduction in the levels of epidermal growth factor receptor (EGFR). Treatment of cells with gefitinib and erlotinib, inhibitors of EGFR, or transient transfection of SCC13 cells with EGFR small interfering RNA, also inhibited invasion of these cells. The inhibition of cell invasion by GSPs was associated with the inhibition of the phosphorylation of ERK1/2, a member of mitogen-activated protein kinase family. Treatment of cells with UO126, an inhibitor of MEK, also inhibited the invasion potential of SCC13 cells. Additionally, inhibition of human cutaneous HNSCC cell invasion by GSPs was associated with reversal of epithelial-to-mesenchymal transition (EMT) process, which resulted in an increase in the levels of epithelial biomarker (E-cadherin) while loss of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in cells. Similar effect on EMT biomarkers was also observed when cells were treated with erlotinib. The results obtained from this study indicate that grape seed proanthocyanidins have the ability to inhibit the invasion of human cutaneous HNSCC cells by targeting the EGFR expression and reversing the

  12. Long noncoding RNA SPRY4-IT1 promotes esophageal squamous cell carcinoma cell proliferation, invasion, and epithelial-mesenchymal transition.

    Science.gov (United States)

    Cui, Fei; Wu, Duoguang; He, Xiaotian; Wang, Wenjian; Xi, Jingle; Wang, Minghui

    2016-08-01

    The biology of esophageal squamous cell carcinoma (ESCC) remains poorly understood. Long noncoding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including ESCC. SPRY4-IT1 has been recently revealed as oncogenic regulator or tumor suppressors in different cancers; however, whether SPRY4-IT1 is involved in ESCC remains poorly understood. To investigate the role of SPRY4-IT1 in ESCC, we evaluated the SPRY4-IT1 expression levels in a series of ESCC patients and a panel of ESCC cell line using qRT-PCR. CCK8 and colony formation assay were performed to assess the effect of SPRY4-IT1siRNA on cell proliferation, migration, and invasion of ESCC cell lines. SPRY4-IT1 expression was upregulated in ESCC tissues and the higher expression of SPRY4-IT1 was significantly correlated with tumor grade, depth of invasion, and lymph node metastasis. Moreover, silencing of SPRY4-IT1 expression inhibited ESCC cell proliferation, colony formation, migration, and invasion. Therefore, our study indicates that SPRY4-IT1 promotes proliferation and migration of ESCC cells and is a potential oncogene of ESCC.

  13. The EhCPADH112 complex of Entamoeba histolytica interacts with tight junction proteins occludin and claudin-1 to produce epithelial damage.

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    Abigail Betanzos

    Full Text Available Entamoeba histolytica, the protozoan responsible for human amoebiasis, causes between 30,000 and 100,000 deaths per year worldwide. Amoebiasis is characterized by intestinal epithelial damage provoking severe diarrhea. However, the molecular mechanisms by which this protozoan causes epithelial damage are poorly understood. Here, we studied the initial molecular interactions between the E. histolytica EhCPADH112 virulence complex and epithelial MDCK and Caco-2 cells. By confocal microscopy, we discovered that after contact with trophozoites or trophozoite extracts (TE, EhCPADH112 and proteins forming this complex (EhCP112 and EhADH112 co-localize with occludin and claudin-1 at tight junctions (TJ. Immunoprecipitation assays revealed interaction between EhCPADH112 and occludin, claudin-1, ZO-1 and ZO-2. Overlay assays confirmed an interaction of EhCP112 and EhADH112 with occludin and claudin-1, whereas only EhADH112 interacted also with ZO-2. We observed degradation of all mentioned TJ proteins after incubation with TE. Importantly, inhibiting proteolytic activity or blocking the complex with a specific antibody not only prevented TJ protein degradation but also epithelial barrier disruption. Furthermore, we discovered that TE treatment induces autophagy and apoptosis in MDCK cells that could contribute to the observed barrier disruption. Our results suggest a model in which epithelial damage caused by E. histolytica is initiated by the interaction of EhCP112 and EhADH112 with TJ proteins followed by their degradation. Disruption of TJs then induces increased paracellular permeability, thus facilitating the entry of more proteases and other parasite molecules leading eventually to tissue destruction.

  14. Transforming growth factor-alpha abrogates glucocorticoid-stimulated tight junction formation and growth suppression in rat mammary epithelial tumor cells.

    Science.gov (United States)

    Buse, P; Woo, P L; Alexander, D B; Cha, H H; Reza, A; Sirota, N D; Firestone, G L

    1995-03-24

    The glucocorticoid and transforming growth factor-alpha (TGF-alpha) regulation of growth and cell-cell contact was investigated in the Con8 mammary epithelial tumor cell line derived from a 7,12-dimethylbenz(alpha)anthracene-induced rat mammary adenocarcinoma. In Con8 cell monolayers cultured on permeable filter supports, the synthetic glucocorticoid, dexamethasone, coordinately suppressed [3H]thymidine incorporation, stimulated monolayer transepithelial electrical resistance (TER), and decreased the paracellular leakage of [3H]inulin or [14C]mannitol across the monolayer. These processes dose dependently correlated with glucocorticoid receptor occupancy and function. Constitutive production of TGF-alpha in transfected cells or exogenous treatment with TGF-alpha prevented the glucocorticoid growth suppression response and disrupted tight junction formation without affecting glucocorticoid responsiveness. Treatment with hydroxyurea or araC demonstrated that de novo DNA synthesis is not a requirement for the growth factor disruption of tight junctions. Immunofluorescence analysis revealed that the ZO-1 tight junction protein is localized exclusively at the cell periphery in dexamethasone-treated cells and that TGF-alpha caused-ZO-1 to relocalize from the cell periphery back to a cytoplasmic compartment. Taken together, our results demonstrate that glucocorticoids can coordinately regulate growth inhibition and cell-cell contact of mammary tumor cells and that TGF-alpha, can override both effects of glucocorticoids. These results have uncovered a novel functional "cross-talk" between glucocorticoids and TGF-alpha which potentially regulates the proliferation and differentiation of mammary epithelial cells.

  15. Bardoxolone methyl induces apoptosis and autophagy and inhibits epithelial-to-mesenchymal transition and stemness in esophageal squamous cancer cells

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    Wang YY

    2015-02-01

    Full Text Available Yan-Yang Wang,1,2 Yin-Xue Yang,3 Ren Zhao,1 Shu-Ting Pan,2,4 Hong Zhe,1 Zhi-Xu He,5 Wei Duan,6 Xueji Zhang,7 Tianxin Yang,8 Jia-Xuan Qiu,4 Shu-Feng Zhou2,51Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 4Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 5Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, People’s Republic of China; 6School of Medicine, Deakin University, Waurn Ponds, VIC, Australia; 7Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China; 8Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USAAbstract: Natural and synthetic triterpenoids have been shown to kill cancer cells via multiple mechanisms. The therapeutic effect and underlying mechanism of the synthetic triterpenoid bardoxolone methyl (C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; CDDO-Me on esophageal cancer are unclear. Herein, we aimed to investigate the anticancer effects and underlying mechanisms of CDDO-Me in human esophageal squamous cell carcinoma (ESCC cells. Our study showed that CDDO-Me suppressed the proliferation and arrested cells in G2/M phase, and induced apoptosis in human ESCC Ec109 and KYSE70 cells. The G2/M arrest was accompanied with upregulated p21Waf1/Cip1 and p53 expression. CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl, B-cell lymphoma 2 (Bcl-2

  16. Giant epithelial malignancies (basal cell carcinoma, squamous cell carcinoma: A series of 20 tumors from a single center

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    Uwe Wollina

    2012-01-01

    Full Text Available Background: Among nonmelanoma skin cancer (NMSC, basal cell carcinoma (BCC, and squamous cell carcinoma (SCC are the most common. Giant NMSCs have occasionally reported in the medical literature with particular problems related to diagnosis and treatment. The aim of this study was to analyze patients, treatment, and outcome with giant BCC/SCC. Materials and Methods: We analyzed our files between January 1, 2008, and December 31, 2011, of an academic teaching hospital in the dermatology department. Patients were analyzed according to demographic factors, clinical presentation, histopathology, treatment, and outcome. American Society of Anesthesiology physical status system was used to assess the fitness of patients before surgery. Results: The frequency of giant NMSC was estimated as 0.4% for both tumor entities. 80% of giant BCC patients were female and 100% of giant SCC patients were male. The mean age was 81.5 ± 8.5 years for BCC and 79.5 ± 11.4 years for SCC. The major anatomical site was the scalp. Four of 10 BCCs were classified metatypic (basosquamous. Perineural infiltration was seen in 5 NMSCs. Seventy percent of patients had an ASA score ≥3. Surgery was performed in general anaesthesia in 5 (BCC and 6 (SCC patients, respectively. All other patients were operated in local or tumescence anesthesia. Blood transfusions were necessary in five patients. The primary treatment was delayed Mohs technique. Defect closure was realized with rotational flaps in most cases. Neoadjuvant chemoimmune therapy and adjuvant combined cetuximab/radiotherapy have been performed in three patients. We observed three deaths, all unrelated to NMSC. 75% of patients achieved complete remission. Conclusions: Giant NMSC is uncommon but not rare. These tumors are high-risk subtypes. Treatment needs an interdisciplinary approach.

  17. Nucleus Accumbens-Associated Protein 1 Expression Has Potential as a Marker for Distinguishing Oral Epithelial Dysplasia and Squamous Cell Carcinoma.

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    Joji Sekine

    Full Text Available Oral epithelial dysplasia (OED and carcinoma in situ (CIS are defined by dysplastic cells in the epithelium. Over a third of oral squamous cell carcinoma (OSCC patients present with associated OED. However, accurate histopathological diagnosis of such lesions is difficult. Nucleus accumbens-associated protein 1 (NAC1 is a member of the Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex family of proteins, and is overexpressed in OSCC. This study aimed to determine whether NAC1 has the potential to be used as a marker to distinguish OED and OSCC.The study included 114 patients (64 men, 50 women. There were 67, 10, and 37 patients with OED, CIS, and OSCC, respectively. NAC1 labeling indices (LIs and immunoreactivity intensities (IRI were evaluated. The patients' pathological classification was significantly associated with age, sex, NAC1 LIs, and NAC1 IRI (p = 0.025, p = 0.022, p 50% positivity the sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV were 0.766, 0.910, 0.857, and 0.847, respectively. For NAC1 IRI with ≤ 124 positive pixels, the sensitivity, specificity, PPV, and NPV were 0.787, 0.866, 0.804, and 0.853, respectively. Though there are several potential limitations to this study and the results were obtained from a retrospective analysis of a single site cohort, the data suggest that the NAC1 LIs/IRI is a strong predictor of CIS/OSCC.NAC1 has potential as a marker for distinguishing OED from CIS/OSCC.

  18. Valproic acid inhibits irradiation-induced epithelial-mesenchymal transition and stem cell-like characteristics in esophageal squamous cell carcinoma

    Science.gov (United States)

    Kanamoto, Ayako; Ninomiya, Itasu; Harada, Shinichi; Tsukada, Tomoya; Okamoto, Koichi; Nakanuma, Shinichi; Sakai, Seisho; Makino, Isamu; Kinoshita, Jun; Hayashi, Hironori; Oyama, Katsunobu; Miyashita, Tomoharu; Tajima, Hidehiro; Takamura, Hiroyuki; Fushida, Sachio; Ohta, Tetsuo

    2016-01-01

    Esophageal carcinoma is one of the most aggressive malignancies, and is characterized by poor response to current therapy and a dismal survival rate. In this study we investigated whether irradiation induces epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC) TE9 cells and whether the classic histone deacetylase (HDAC) inhibitor valproic acid (VPA) suppresses these changes. First, we showed that 2 Gy irradiation induced spindle cell-like morphologic changes, decreased expression of membranous E-cadherin, upregulated vimentin expression, and altered the localization of β-catenin from its usual membrane-bound location to cytoplasm in TE9 cells. Irradiation induced upregulation of transcription factors including Slug, Snail, and Twist, which regulate EMT. Stimulation by irradiation resulted in increased TGF-β1 and HIF-1α expression and induced Smad2 and Smad3 phosphorylation. Furthermore, irradiation enhanced CD44 expression, indicating acquisition of cancer stem-like cell properties. In addition, irradiation enhanced invasion and migration ability with upregulation of matrix metalloproteinases. These findings indicate that single-dose irradiation can induce EMT in ESCC cells. Second, we found that treatment with 1 mM VPA induced reversal of EMT caused by irradiation in TE9 cells, resulting in attenuated cell invasion and migration abilities. These results suggest that VPA might have clinical value to suppress irradiation-induced EMT. The reversal of EMT by HDAC inhibitors may be a new therapeutic strategy to improve the effectiveness of radiotherapy in ESCC by inhibiting the enhancement of invasion and metastasis.

  19. Salinomycin induces cell death and differentiation in head and neck squamous cell carcinoma stem cells despite activation of epithelial-mesenchymal transition and Akt

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    Kuo Selena Z

    2012-11-01

    Full Text Available Abstract Background Cancer stem cells (CSC are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC stem cells. Methods MTS and TUNEL assays were used to study cell proliferation and apoptosis as a function of salinomycin exposure in JLO-1, a putative HNSCC stem cell culture. MTS and trypan blue dye exclusion assays were performed to investigate potential drug interactions between salinomycin and cisplatin or paclitaxel. Stem cell-like phenotype was measured by mRNA expression of stem cell markers, sphere-forming capacity, and matrigel invasion assays. Immunoblotting was also used to determine expression of epithelial-mesenchymal transition (EMT markers and Akt phosphorylation. Arrays by Illumina, Inc. were used to profile microRNA expression as a function of salinomycin dose. Results In putative HNSCC stem cells, salinomycin was found to significantly inhibit cell viability, induce a 71.5% increase in levels of apoptosis, elevate the Bax/Bcl-2 ratio, and work synergistically with cisplatin and paclitaxel in inducing cell death. It was observed that salinomycin significantly inhibited sphere forming-capability and repressed the expression of CD44 and BMI-1 by 3.2-fold and 6.2-fold, respectively. Furthermore, salinomycin reduced invasion of HNSCC stem cells by 2.1 fold. Contrary to expectations, salinomycin induced the expression of EMT markers Snail, vimentin, and Zeb-1, decreased expression of E-cadherin, and also induced phosphorylation of Akt and its downstream targets GSK3-β and mTOR. Conclusions These results demonstrate that in HNSCC cancer stem cells, salinomycin can cause cell death and

  20. Epithelial-mesenchymal transition (EMT) phenotype at invasion front of squamous cell carcinoma of the penis influences oncological outcomes.

    Science.gov (United States)

    da Cunha, Isabela Werneck; Souza, Maria José L; da Costa, Walter Henriques; Amâncio, Alice M; Fonseca, Francisco Paulo; Zequi, Stenio de Cassio; Lopes, Ademar; Guimarães, Gustavo Cardoso; Soares, Fernando

    2016-10-01

    Our aims were to evaluate epithelial-mesenchymal transition (EMT) as a useful prognostic marker in penile carcinoma (PC), and establish an objective criterion to define EMT in PC specimens. A total of 149 consecutive cases surgically treated for PC were retrospectively selected. E-cadherin (E-CAD) and vimentin immunohistochemical expressions were evaluated. A combined analysis was performed using both markers to determine EMT status. To establish a normal control to E-CAD expression, we included 14 cases from circumcisions from patients without any neoplastic disease and 77 cases of tumor-free margins. The analyses of tumor samples were evaluated in 2 different areas of the tumor. The first one was in the tumor core. The second analyses were performed on the deepest infiltrative edge of the tumor, nominated invasion front. Cases were classified into EMT absent group, partial EMT group and complete EMT group. Overall survival (OS) and cancer-specific survival (CSS) were analyzed. Kaplan-Meier curves and the log-rank test were used. Cox proportional hazards model was used to determine which variables influenced survival. Tumor specimens presented a significant loss of expression of E-CAD when compared with normal epithelium. Vimentin expression in more than 10% of tumor cells was observed in 50 cases. EMT status was associated with histologic grade, pattern of invasion, lymph node metastasis, and perineural and vascular invasion. Further, 10-year OS and CSS rates in patients with presence and absence of complete EMT status were 38.0% and 55.6%; and 48.0% and 91.9%, respectively. EMT status significantly affected CSS and OS rates even after patients were grouped based on lymph node involvement status. The presence of complete EMT status was associated with both CSS and OS rates. Patients in the complete EMT group had a higher risk of death from cancer (hazard ratio = 7.6, PEMT in PC. We encourage the study of EMT markers in other centers to validate our findings and

  1. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis.

    Science.gov (United States)

    Nighot, Prashant; Al-Sadi, Rana; Rawat, Manmeet; Guo, Shuhong; Watterson, D Martin; Ma, Thomas

    2015-12-15

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9(-/-) mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9(-/-) mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9(-/-) mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK(-/-) mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9(-/-) mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.

  2. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

    Science.gov (United States)

    Nighot, Prashant; Al-Sadi, Rana; Guo, Shuhong; Watterson, D. Martin; Ma, Thomas

    2015-01-01

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/− mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/− mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/− mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/− mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/− mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK. PMID:26514773

  3. Expression of C4.4A, a structural uPAR homolog, reflects squamous epithelial differentiation in the adult mouse and during embryogenesis

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Jacobsen, Benedikte; Hald, Andreas

    2011-01-01

    by a comprehensive immunohistochemical mapping. This task was accomplished by staining paraffin-embedded tissues with a specific rabbit polyclonal anti-C4.4A antibody. In the adult mouse, C4.4A was predominantly expressed in the suprabasal layers of the squamous epithelia of the oral cavity, esophagus, non-glandular...... expression first appears in the developing squamous epithelium at embryonic day 13.5. This anatomical location of C4.4A is thus concordant with a possible functional role in early differentiation of stratified squamous epithelia....

  4. Cancer stem-like cells enriched with CD29 and CD44 markers exhibit molecular characteristics with epithelial-mesenchymal transition in squamous cell carcinoma.

    Science.gov (United States)

    Geng, Songmei; Guo, Yuanyuan; Wang, Qianqian; Li, Lan; Wang, Jianli

    2013-01-01

    Increasing evidences have indicated that only a phenotypic subset of cancer cells, termed as the cancer stem cells (CSCs), is capable of initiating tumor growth and provide a reservoir of cells that cause tumor recurrence after therapy. Epithelial-mesenchymal transition (EMT), a cell type change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, plays a critical role not only in tumor metastasis but also in tumor recurrence and contributes to drug resistance. Accumulating evidence has shown that cells with an EMT phenotype are rich sources for CSCs, suggesting a biological link between EMT and CSCs; thus study on the link will help understand the cellular and molecular mechanisms of tumor metastasis and drug resistance. CD29 is involved in EMT through cross-talk with cadherins and CD44 has been reported as a successful used marker for CSCs. Here, we try to address whether combination of CD29 and CD44 could be used to identify cancer stem-like cells undergoing EMT in squamous cell carcinoma (SCC) and compare the molecular differences between CD29high/CD44high and CD29low/CD44low cells in SCC. Expression pattern of CD29 and CD44 was analyzed in tissues of skin SCC and cultured A431 cells by immunostaining. Subtype cells of CD29high/CD44high and CD29low/CD44low A431 were sorted by fluorescence-activated cell sorting and proliferating abilities were assayed by cell counting, colony forming and tumorigenicity in NOD/SCID mice. Finally, to probe more deeply into the molecular differences between CD29high/CD44high and CD29low/CD44low A431 cells, gene microarray analysis was applied to compare gene expression profiling. Staining of CD29 and CD44 showed similar heterogeneous expression pattern with positive cells located in the invasion front of SCC tissue as well as in cultured A431 cells. Sorted CD29high/CD44high A431 cells had higher proliferating ability in vitro and in NOD/SCID mice as compared with CD29low/CD44low cells. Gene profiling

  5. Restoration of E-cadherin Cell-Cell Junctions Requires Both Expression of E-cadherin and Suppression of ERK MAP Kinase Activation in Ras-Transformed Breast Epithelial Cells

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    Quanwen Li

    2008-12-01

    Full Text Available E-cadherin is a main component of the cell-cell adhesion junctions that play a principal role in maintaining normal breast epithelial cell morphology. Breast and other cancers that have up-regulated activity of Ras are often found to have down-regulated or mislocalized E-cadherin expression. Disruption of E-cadherin junctions and consequent gain of cell motility contribute to the process known as epithelial-to-mesenchymal transition (EMT. Enforced expression of E-cadherin or inhibition of Ras-signal transduction pathway has been shown to be effective in causing reversion of EMT in several oncogene-transformed and cancer-derived cell lines. In this study, we investigated MCF10A human breast epithelial cells and derivatives that were transformed with either activated H-Ras or N-Ras to test for the reversion of EMT by inhibition of Ras-driven signaling pathways. Our results demonstrated that inhibition of mitogen-activated protein kinase (MAPK kinase, but not PI3-kinase, Rac, or myosin light chain kinase, was able to completely restore E-cadherin cell-cell junctions and epithelial morphology in cell lines with moderate H-Ras expression. In MCF10A cells transformed by a high-level expression of activated H-Ras or N-Ras, restoration of E-cadherin junction required both the enforced reexpression of E-cadherin and suppression of MAPK kinase. Enforced expression of E-cadherin alone did not induce reversion from the mesenchymal phenotype. Our results suggest that Ras transformation has at least two independent actions to disrupt E-cadherin junctions, with effects to cause both mislocalization of E-cadherin away from the cell surface and profound decrease in the expression of E-cadherin.

  6. The protein kinase A pathway contributes to Hg2+-induced alterations in phosphorylation and subcellular distribution of occludin associated with increased tight junction permeability of salivary epithelial cell monolayers.

    Science.gov (United States)

    Kawedia, Jitesh D; Jiang, Mengmeng; Kulkarni, Amit; Waechter, Holly E; Matlin, Karl S; Pauletti, Giovanni M; Menon, Anil G

    2008-09-01

    Hg(2+) is commonly used as an inhibitor of many aquaporins during measurements of transcellular water transport. To investigate whether it could also act on the paracellular water transport pathway, we asked whether addition of Hg(2+) affected transport of radiolabeled probes through tight junctions of a salivary epithelial cell monolayer. Inclusion of 1 mM Hg(2+) decreased transepithelial electrical resistance by 8-fold and augmented mannitol and raffinose flux by 13-fold, which translated into an estimated 44% increase in pore radius at the tight junction. These Hg(2+)-induced effects could be partially blocked by the protein kinase A (PKA) inhibitor N-[2-((p-bromocinnamyl) amino) ethyl]-5-isoquinolinesulfonamide, 2HCl (H89), suggesting that both-PKA dependent and PKA-independent mechanisms contribute to tight junction regulation. Western blot analyses showed a 2-fold decrease in tight junction-associated occludin after Hg(2+) treatment and the presence of a novel hyperphosphorylated form of occludin in the cytoplasmic fraction. These findings were corroborated by confocal imaging. The results from this study reveal a novel contribution of the PKA pathway in Hg(2+)-induced regulation of tight junction permeability in the salivary epithelial barrier. Therapeutically, this could be explored for pharmacological intervention in the treatment of dry mouth, Sjögren's syndrome, and possibly other disorders of fluid transport.

  7. Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization.

    Science.gov (United States)

    Nunan, Robert; Campbell, Jessica; Mori, Ryoichi; Pitulescu, Mara E; Jiang, Wen G; Harding, Keith G; Adams, Ralf H; Nobes, Catherine D; Martin, Paul

    2015-11-17

    For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man.

  8. miR156a Mimic Represses the Epithelial-Mesenchymal Transition of Human Nasopharyngeal Cancer Cells by Targeting Junctional Adhesion Molecule A.

    Directory of Open Access Journals (Sweden)

    Yunhong Tian

    Full Text Available MicroRNAs (miRNAs have been documented as having an important role in the development of cancer. Broccoli is very popular in large groups of the population and has anticancer properties. Junctional adhesion molecule A (JAMA is preferentially concentrated at tight junctions and influences cell morphology and migration. Epithelial-mesenchymal transition (EMT is a developmental program associated with cancer progression and metastasis. In this study we aimed to investigate the role of miRNAs from broccoli in human nasopharyngeal cancer (NPC. We demonstrated that a total of 84 conserved miRNAs and 184 putative novel miRNAs were found in broccoli by sequencing technology. Among these, miR156a was expressed the most. In addition, synthetic miR156a mimic inhibited the EMT of NPC cells in vitro. Furthermore, it was confirmed that JAMA was the target of miR156a mimic as validated by 3' UTR luciferase reporter assays and western blotting. Knockdown of JAMA was consistent with the effects of miR156a mimic on the EMT of NPC, and the up-regulation of JAMA could partially restore EMT repressed by miR156a mimic. In conclusion, these results indicate that the miR156a mimic inhibits the EMT of NPC cells by targeting the 3' UTR of JAMA. These miRNA profiles of broccoli provide a fundamental basis for further research. Moreover, the discovery of miR156a may have clinical implications for the treatment of patients with NPC.

  9. 21-Benzylidene Digoxin: A Proapoptotic Cardenolide of Cancer Cells That Up-Regulates Na,K-ATPase and Epithelial Tight Junctions

    Science.gov (United States)

    Rocha, Sayonarah C.; Pessoa, Marco T. C.; Neves, Luiza D. R.; Alves, Silmara L. G.; Silva, Luciana M.; Santos, Herica L.; Oliveira, Soraya M. F.; Taranto, Alex G.; Comar, Moacyr; Gomes, Isabella V.; Santos, Fabio V.; Paixão, Natasha; Quintas, Luis E. M.; Noël, François; Pereira, Antonio F.; Tessis, Ana C. S. C.; Gomes, Natalia L. S.; Moreira, Otacilio C.; Rincon-Heredia, Ruth; Varotti, Fernando P.; Blanco, Gustavo; Villar, Jose A. F. P.; Contreras, Rubén G.; Barbosa, Leandro A.

    2014-01-01

    Cardiotonic steroids are used to treat heart failure and arrhythmia and have promising anticancer effects. The prototypic cardiotonic steroid ouabain may also be a hormone that modulates epithelial cell adhesion. Cardiotonic steroids consist of a steroid nucleus and a lactone ring, and their biological effects depend on the binding to their receptor, Na,K-ATPase, through which, they inhibit Na+ and K+ ion transport and activate of several intracellular signaling pathways. In this study, we added a styrene group to the lactone ring of the cardiotonic steroid digoxin, to obtain 21-benzylidene digoxin (21-BD), and investigated the effects of this synthetic cardiotonic steroid in different cell models. Molecular modeling indicates that 21-BD binds to its target Na,K-ATPase with low affinity, adopting a different pharmacophoric conformation when bound to its receptor than digoxin. Accordingly, 21-DB, at relatively high µM amounts inhibits the activity of Na,K-ATPase α1, but not α2 and α3 isoforms. In addition, 21-BD targets other proteins outside the Na,K-ATPase, inhibiting the multidrug exporter Pdr5p. When used on whole cells at low µM concentrations, 21-BD produces several effects, including: 1) up-regulation of Na,K-ATPase expression and activity in HeLa and RKO cancer cells, which is not found for digoxin, 2) cell specific changes in cell viability, reducing it in HeLa and RKO cancer cells, but increasing it in normal epithelial MDCK cells, which is different from the response to digoxin, and 3) changes in cell-cell interaction, altering the molecular composition of tight junctions and elevating transepithelial electrical resistance of MDCK monolayers, an effect previously found for ouabain. These results indicate that modification of the lactone ring of digoxin provides new properties to the compound, and shows that the structural change introduced could be used for the design of cardiotonic steroid with novel functions. PMID:25290152

  10. 21-Benzylidene digoxin: a proapoptotic cardenolide of cancer cells that up-regulates Na,K-ATPase and epithelial tight junctions.

    Directory of Open Access Journals (Sweden)

    Sayonarah C Rocha

    Full Text Available Cardiotonic steroids are used to treat heart failure and arrhythmia and have promising anticancer effects. The prototypic cardiotonic steroid ouabain may also be a hormone that modulates epithelial cell adhesion. Cardiotonic steroids consist of a steroid nucleus and a lactone ring, and their biological effects depend on the binding to their receptor, Na,K-ATPase, through which, they inhibit Na+ and K+ ion transport and activate of several intracellular signaling pathways. In this study, we added a styrene group to the lactone ring of the cardiotonic steroid digoxin, to obtain 21-benzylidene digoxin (21-BD, and investigated the effects of this synthetic cardiotonic steroid in different cell models. Molecular modeling indicates that 21-BD binds to its target Na,K-ATPase with low affinity, adopting a different pharmacophoric conformation when bound to its receptor than digoxin. Accordingly, 21-DB, at relatively high µM amounts inhibits the activity of Na,K-ATPase α1, but not α2 and α3 isoforms. In addition, 21-BD targets other proteins outside the Na,K-ATPase, inhibiting the multidrug exporter Pdr5p. When used on whole cells at low µM concentrations, 21-BD produces several effects, including: 1 up-regulation of Na,K-ATPase expression and activity in HeLa and RKO cancer cells, which is not found for digoxin, 2 cell specific changes in cell viability, reducing it in HeLa and RKO cancer cells, but increasing it in normal epithelial MDCK cells, which is different from the response to digoxin, and 3 changes in cell-cell interaction, altering the molecular composition of tight junctions and elevating transepithelial electrical resistance of MDCK monolayers, an effect previously found for ouabain. These results indicate that modification of the lactone ring of digoxin provides new properties to the compound, and shows that the structural change introduced could be used for the design of cardiotonic steroid with novel functions.

  11. Apoptosis detected by tissue microarray in cervical squamous epithelial lesions%组织芯片技术检测宫颈鳞状上皮病变中细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    林静; 乐江华; 寥芝玲

    2011-01-01

    Objective: To study the condition and significance of apoptosis in cervical squamous epithelial lesions. Methods: 53 cervical specimens were selected from the hospital from January 2008 to October 2009 to prepare tissue microarray, including 9 normal specimens, 32 specimens of CIN and 12 specimens of cervical squamous cell carcinoma; TUNEL method was used to detect apoptosis. Results; The positive rates of apoptosis were 0% (0/9) in normal cervix group, 15. 62% (5/32) in CIN group, 66. 67% (8/12) in squamous cell carcinoma group; there was significant difference among the three groups (P <0. 01) . Conclusion: The phenomenon of apoptosis becomes clear with the aggravation of cervical squamous epithelial lesions, TUNEL technique has the advantages of high quality, high efficiency and reliability for tissue microarray detection.%目的:研究宫颈鳞状上皮病变中细胞凋亡的情况及其意义.方法:选择2008年1月~2009年10月桂林医学院附属医院53例宫颈组织制成组织芯片,其中正常9例,CIN 32例,鳞状细胞癌12例;应用TUNEL法检测细胞凋亡情况.结果:凋亡阳性率依次为:正常组0% (0/9),CIN组15.62% (5/32),鳞状细胞癌66.67%(8/12);正常组、CIN组与癌症组凋亡阳性率比较差异有统计学意义(P<0.01).结论:细胞凋亡现象随着宫颈鳞状上皮病变的发展逐渐明显,应用TUNEL法检测宫颈组织芯片,具有优质、高效、结果可靠的特点.

  12. Bacterial interference with host epithelial junctional complexes: Probiotic bacteria vs. A/E lesion-forming Escherichia coli

    Directory of Open Access Journals (Sweden)

    TANIA TOPOUZOVA-HRISTOVA

    2012-01-01

    Full Text Available During colonization, enteropathogenic (EPEC and enterohaemorrhagic (EHEC Escherichia coli are capable to manipulate host cytoskeleton and colonize gut epithelia by a specific mode of attachment known as the attaching and effacing lesion (A/E lesion. While actin rearrangements during A/E lesion formation have been extensively investigated, the possible alterations of other cytoskeletal elements like those comprising the intercellular junctional complexes (JC of polarized cells during infection have only lately attracted attention. The present mini-review addresses the opposite effects of two groups of bacteria, A/E lesion-forming pathogenic E. coli and probiotic bacterial strains, on JC. JC are important in maintaining gut barrier functions. EPEC and EHEC can disrupt JC which as a consequence leads to reduction in the transepitelial electrical resistance (TER and an increase of the permeability to macromolecules. Probiotic bacteria on the other hand stabilize JC thus increasing TER and reducing permeability to macromolecular markers. Probiotic strains can protect JC integrity of polarized cells from the damage caused by EPEC or EHEC. Together with the promise of these results, of concern is the fact that the outcome of the studies can differ dependent on experimental protocols. Studies with living bacteria and different strain combinations have also put forward strain specific effects. Therefore, an important practical item for future studies is the identification of the molecules synthesized by probiotic bacteria that may be active on JC stability.

  13. Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization

    Directory of Open Access Journals (Sweden)

    Robert Nunan

    2015-11-01

    Full Text Available For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man.

  14. 病毒在眼部鳞状上皮增生性疾病发病中的作用%The role of virus in the pathogenesis of ocular squamous epithelial hyperplasia

    Institute of Scientific and Technical Information of China (English)

    张夏; 王薇

    2014-01-01

    眼部鳞状上皮增生性疾病在眼部肿物中占绝大部分.病毒是很多眼部鳞状上皮增生性疾病的病因.人乳头瘤病毒可通过早期蛋白编码区蛋白抑制角质细胞凋亡,促进角质细胞增生,从而导致眼部鳞状上皮乳头状瘤、寻常疣及角化棘皮瘤的发生.人乳头瘤病毒DNA可通过PCR在以上几种疾病的病灶中被检测出来.目前干扰素已被应用于以上几种疾病的治疗中,并在长期随访中被证明有较好疗效.人类免疫缺陷病毒血清学阳性可显著提高结膜角膜上皮内瘤变及鳞状细胞癌的发病率,但具体机制尚不明了.传染性软疣病毒编码的蛋白可抑制角质细胞凋亡并促进肿瘤发生,但目前尚无特效药物治疗.%Squamous epithelial hyperplasia diseases contribute to the biggest part of tumor-like lesions of the eye.Many squamous epithelial hyperplasia diseases are caused by virus as pathogen.Human papilla virus(HPV) suppresses the apoptosis of keratinocytes and enhances the hyperplasia of keratinocytes through early protein coding region thus causes the onset of squamous epithelial papilloma,verruca vulgaris and keratoacanthoma.HPV-DNA can be detected in the lesion of those diseases by PCR.Currently the interferon has been applied into the treatment of the above diseases and acquired reasonable effectiveness in long-term follow-ups.Serological positive of human immunodeficiency virus can remarkably raise the morbidity of conjunctival and corneal intraepithelial neoplasm and squamous cell carcinoma.However the pathogenesis remains unknown.The apoptosis of keratinocytes can be suppressed by the mollascus contagiosum virus coded protein so as to promote the onset of tumor.However no treatment is available.

  15. Molecular profiling of tumour budding implicates TGFβ-mediated epithelial-mesenchymal transition as a therapeutic target in oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Jensen, D H; Dabelsteen, E; Specht, L;

    2015-01-01

    collected from oral squamous cell carcinoma (OSCC) specimens, using laser capture microdissection, and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature, comprising factors involved...

  16. Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29.

    Science.gov (United States)

    Jeong, Chang Hee; Seok, Jin Sil; Petriello, Michael C; Han, Sung Gu

    2017-03-15

    Arsenic is a naturally occurring metalloid that often is found in foods and drinking water. Human exposure to arsenic is associated with the development of gastrointestinal problems such as fluid loss, diarrhea and gastritis. Arsenic is also known to induce toxic responses including oxidative stress in cells of the gastrointestinal track. Tight junctions (TJs) regulate paracellular permeability and play a barrier role by inhibiting the movement of water, solutes and microorganisms in the paracellular space. Since oxidative stress and TJ damage are known to be associated, we examined whether arsenic produces TJ damage such as downregulation of claudins in the human colorectal cell line, HT-29. To confirm the importance of oxidative stress in arsenic-induced TJ damage, effects of the antioxidant compound (e.g., N-acetylcysteine (NAC)) were also determined in cells. HT-29 cells were treated with arsenic trioxide (40μM, 12h) to observe the modified expression of TJ proteins. Arsenic decreased expression of TJ proteins (i.e., claudin-1 and claudin-5) and transepithelial electrical resistance (TEER) whereas pretreatment of NAC (5-10mM, 1h) attenuated the observed claudins downregulation and TEER. Arsenic treatment produced cellular oxidative stress via superoxide generation and lowering glutathione (GSH) levels, while NAC restored cellular GSH levels and decreased oxidative stress. Arsenic increased phosphorylation of p38 and nuclear translocation of nuclear factor-kappa B (NF-κB) p65, while NAC attenuated these intracellular events. Results demonstrated that arsenic can damage intestinal epithelial cells by proinflammatory process (oxidative stress, p38 and NF-κB) which resulted in the downregulation of claudins and NAC can protect intestinal TJs from arsenic toxicity.

  17. Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: An immunohistochemical study.

    Science.gov (United States)

    Ayva, Sebnem Kupana; Karabulut, Ayse Anil; Akatli, Ayşe Nur; Atasoy, Pinar; Bozdogan, Onder

    2013-10-01

    Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44 specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS), 13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed), and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each marker was quantified using a calculated immunohistochemical/histologic score (H-score). Correlations were analyzed for the marker H-scores in each study group. Associations between H-scores and histopathologic parameters were also evaluated. CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS, and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and MMP-2n H-scores were significantly higher in peritumoral epidermis than in invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in the peritumoral SCCs. CD147 H-score was positively correlated with tumor differentiation in SCC. The findings suggest that overexpression of CD147 plays a role in the development of SCC.

  18. Diurnal variation of tight junction integrity associates inversely with matrix metalloproteinase expression in Xenopus laevis corneal epithelium: implications for circadian regulation of homeostatic surface cell desquamation.

    Directory of Open Access Journals (Sweden)

    Allan F Wiechmann

    Full Text Available The corneal epithelium provides a protective barrier against pathogen entrance and abrasive forces, largely due to the intercellular junctional complexes between neighboring cells. After a prescribed duration at the corneal surface, tight junctions between squamous surface cells must be disrupted to enable them to desquamate as a component of the tissue homeostatic renewal. We hypothesize that matrix metalloproteinase (MMPs are secreted by corneal epithelial cells and cleave intercellular junctional proteins extracellularly at the epithelial surface. The purpose of this study was to examine the expression of specific MMPs and tight junction proteins during both the light and dark phases of the circadian cycle, and to assess their temporal and spatial relationships in the Xenopus laevis corneal epithelium.Expression of MMP-2, tissue inhibitor of MMP-2 (TIMP-2, membrane type 1-MMP (MT1-MMP and the tight junction proteins occludin and claudin-4 were examined by confocal double-label immunohistochemistry on corneas obtained from Xenopus frogs at different circadian times. Occludin and claudin-4 expression was generally uniformly intact on the surface corneal epithelial cell lateral membranes during the daytime, but was frequently disrupted in small clusters of cells at night. Concomitantly, MMP-2 expression was often elevated in a mosaic pattern at nighttime and associated with clusters of desquamating surface cells. The MMP-2 binding partners, TIMP-2 and MT1-MMP were also localized to surface corneal epithelial cells during both the light and dark phases, with TIMP-2 tending to be elevated during the daytime.MMP-2 protein expression is elevated in a mosaic pattern in surface corneal epithelial cells during the nighttime in Xenopus laevis, and may play a role in homeostatic surface cell desquamation by disrupting intercellular junctional proteins. The sequence of MMP secretion and activation, tight junction protein cleavage, and subsequent surface

  19. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  20. Assessment of Tissue Eosinophilia as a Prognosticator in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma—An Image Analysis Study

    Directory of Open Access Journals (Sweden)

    Megha Jain

    2014-01-01

    Full Text Available Association of tissue eosinophilia with oral squamous cell carcinoma has shown variable results ranging from favourable to unfavourable or even having no influence on prognosis. Also, very few studies have been done to know the role of eosinophils in premalignancy. So the present study investigated role of eosinophilic infiltration in oral precancer and cancer and its possible use as a prognosticator. 60 histopathologically proven cases (20 cases each of metastatic and nonmetastatic oral squamous cell carcinoma and oral leukoplakia with dysplasia of various grades were included. Congo red is used as a special stain for eosinophils. Each specimen slide was viewed under high power in 10 consecutive microscopic fields for counting of eosinophils. As a result, a significant increase in eosinophil count was found in oral carcinomas compared to dysplasia. Nonmetastatic cases showed higher counts than metastatic carcinomas. So, it is concluded that eosinophilia is a favourable histopathological prognostic factor in oral cancer. Moreover, higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion thus suggesting that quantitative assessment of tissue eosinophilia should become a part of the routine histopathological diagnosis for oral precancer and OSCC.

  1. Effect of cisplatin exposure on platinum accumulation and growth inhibition in human neoplastic and normal squamous epithelial cells of the mucosa of the upper-aerodigestive tract

    NARCIS (Netherlands)

    Braakhuis, B.J.M.; Welters, M.J.P.; Cloos, J.; Pankras, J.E.; Smeets, S.J.; Fichtinger-Schepman, A.-M.J.

    1999-01-01

    The aim of the present study was to investigate how normal head and neck epithelial cells (NHNEC) respond to cisplatin compared to their neoplastic counterparts with respect to intracellular platinum (Pt) levels and growth inhibition. A colorimetric assay was used to assess growth inhibition after e

  2. Outer Membrane Vesicles and Soluble Factors Released by Probiotic Escherichia coli Nissle 1917 and Commensal ECOR63 Enhance Barrier Function by Regulating Expression of Tight Junction Proteins in Intestinal Epithelial Cells

    Science.gov (United States)

    Alvarez, Carina-Shianya; Badia, Josefa; Bosch, Manel; Giménez, Rosa; Baldomà, Laura

    2016-01-01

    The gastrointestinal epithelial layer forms a physical and biochemical barrier that maintains the segregation between host and intestinal microbiota. The integrity of this barrier is critical in maintaining homeostasis in the body and its dysfunction is linked to a variety of illnesses, especially inflammatory bowel disease. Gut microbes, and particularly probiotic bacteria, modulate the barrier integrity by reducing gut permeability and reinforcing tight junctions. Probiotic Escherichia coli Nissle 1917 (EcN) is a good colonizer of the human gut with proven therapeutic efficacy in the remission of ulcerative colitis in humans. EcN positively modulates the intestinal epithelial barrier through upregulation and redistribution of the tight junction proteins ZO-1, ZO-2 and claudin-14. Upregulation of claudin-14 has been attributed to the secreted protein TcpC. Whether regulation of ZO-1 and ZO-2 is mediated by EcN secreted factors remains unknown. The aim of this study was to explore whether outer membrane vesicles (OMVs) released by EcN strengthen the epithelial barrier. This study includes other E. coli strains of human intestinal origin that contain the tcpC gene, such as ECOR63. Cell-free supernatants collected from the wild-type strains and from the derived tcpC mutants were fractionated into isolated OMVs and soluble secreted factors. The impact of these extracellular fractions on the epithelial barrier was evaluated by measuring transepithelial resistance and expression of several tight junction proteins in T-84 and Caco-2 polarized monolayers. Our results show that the strengthening activity of EcN and ECOR63 does not exclusively depend on TcpC. Both OMVs and soluble factors secreted by these strains promote upregulation of ZO-1 and claudin-14, and down-regulation of claudin-2. The OMVs-mediated effects are TcpC-independent. Soluble secreted TcpC contributes to the upregulation of ZO-1 and claudin-14, but this protein has no effect on the transcriptional

  3. The EhCPADH112 Complex of Entamoeba histolytica Interacts with Tight Junction Proteins Occludin and Claudin-1 to Produce Epithelial Damage

    OpenAIRE

    Abigail Betanzos; Rosario Javier-Reyna; Guillermina García-Rivera; Cecilia Bañuelos; Lorenza González-Mariscal; Michael Schnoor; Esther Orozco

    2013-01-01

    Entamoeba histolytica, the protozoan responsible for human amoebiasis, causes between 30,000 and 100,000 deaths per year worldwide. Amoebiasis is characterized by intestinal epithelial damage provoking severe diarrhea. However, the molecular mechanisms by which this protozoan causes epithelial damage are poorly understood. Here, we studied the initial molecular interactions between the E. histolytica EhCPADH112 virulence complex and epithelial MDCK and Caco-2 cells. By confocal microscopy, we...

  4. [Treatment of 9 squamous epithelial carcinoma in situ lesions of the conjunctiva (CIN) with mitomycin C eyedrops in cytological and DNA image cytometric control].

    Science.gov (United States)

    Cartsburg, O; Kersten, A; Sundmacher, R; Nadjari, B; Pomjanski, N; Böcking, A

    2001-06-01

    Conjunctival intraepithelial neoplasia (CIN) is a frequent conjunctival tumor. Following excision alone recurrences are frequent. An effective postsurgical recurrence prevention is therefore highly desirable. In this study we aimed to evaluate the effectivity of postsurgical chemotherapy of conjunctival squamous cell carcinoma in situ (CIN) with mitomycin C eyedrops. We introduced the otherwise established diagnostic tools of cytology and DNA-image-cytometry to the diagnosis and therapy-monitoring of CIN. We treated 9 patients with CIN. For diagnosis the results of cytology and cytometry of presurgically obtained brush smears were compared with the histologic evaluation of the excised tissue. After surgery, we administered topical chemotherapy with mitomycin C eye drops 0.02% (MMC). Conjunctival brush smears were again evaluated by cytology and DNA-image-cytometry for postsurgical therapy monitoring. The clinical diagnosis of CIN was fully confirmed by cytology, DNA-image-cytometry and histology respectively in 7 patients. In one patient, the results of the applied diagnostic methods differed in results: Histologic evaluation indicated a moderate dysplasia but DNA-image-cytometry showed significant DNA-aneuploidy unequivocally indicating neoplasia like squamous cell carcinoma. In another patient the preoperatively obtained conjunctival brush smears could not properly analyzed by cytometry but clinical diagnosis was confirmed by histology. MMC-therapy was well tolerated except for a self-limited conjunctivitis. A complete remission of CIN was obtained in 8 of 9 patients (89%) who were free of CIN recurrences during a follow-up period of 27.2 months (11-48). Only one patient suffered from a recurrence 14 months after surgery and after 2 MMC-cycles. Adjuvant topical mitomycin C appears to be effective in the prevention of recurrences of conjunctival CIN after surgical removal. Our results indicate that at least 4 cycles of topical MMC are required to prevent local

  5. Squamous cell carcinoma of the conjunctiva

    Directory of Open Access Journals (Sweden)

    Stephen Gichuhi

    2017-02-01

    Full Text Available Squamous cell carcinoma of the conjunctiva is the end-stage of a spectrum of disease referred to as ocular surface squamous neoplasia (OSSN. OSSN is a malignant disease of the eyes that can lead to loss of vision and, in severe cases, death. The main risk factors for both are exposure to solar ultraviolet radiation outdoors, HIV/AIDS, human papilloma virus and allergic conjunctivitis. The limbal epithelial cells appear to be the progenitors of this disease.

  6. 下咽颈段食管交界癌的喉功能保留及游离空肠修复术%Free jejunum reconstruction and laryngeal preservation for squamous cell carcinoma in the pharyngoesophageal junction

    Institute of Scientific and Technical Information of China (English)

    张彬; 苏纪平; 余济春; 邬振华; 冯志星

    2014-01-01

    目的 尝试采用游离空肠修复技术保留下咽颈段食管交界癌患者的喉功能.方法 2007年8月至2012年12月回顾性分析肿瘤同时位于下咽和颈段食管的13例鳞状细胞癌患者,均进行喉功能保留的外科治疗.原发灶T3期8例,T4期4例,放疗后复发rT2期1例.采用游离空肠部分剖开的方法同时修复下咽和颈段食管.10例患者接受了术后放疗(7例)或放化疗(3例),放疗剂量49~65 Gy,平均56 Gy.结果 Kaplan-Meier方法计算13例患者的3年总生存率为47.9%,无瘤生存率为34.2%.9例(9/13)患者发生手术并发症,包括手术死亡1例和游离空肠坏死1例.5例(5/13)患者长期带气管套管.10例(10/13)患者完全恢复经口进食,全部患者恢复发音.结论 初步经验发现,部分有选择的下咽颈段食管交界癌患者可以运用游离空肠修复技术,保留喉功能,有利于提高患者生活质量.%Objective Try to use free jejunum flaps reconstruction and laryngeal preservation for squamous cell carcinoma (SCC) in the pharyngoesophageal junction.Methods Thirteen patients who underwent resections of SCC in the pharyngoesophageal junction with free jejunal interposition from August 2007 to December 2012 were reviewed.Of them,8 had T3 lesions,4 had T4 lesions,and one had radiation failure with rT2 lesion.Ten patients were treated with postoperative radiotherapy with a average dosage of 56 Gy.Results The 3 year over all survival rate was 47.9% and disease-specific survival rate was 34.2%.The surgical complications occurred in 9 patients (9/13),including one death and one flap failure.Five patients (5/13) had permanent tracheal canulation,10 patients (10/13) resumed oral feeding and all patients achieved reasonable speech.Conclusion Free jejunum interposition can be used to reconstruct surgical defect of SCC in the pharyngoesophageal junction,thus preserving the larynx and ensuring a better quality of life for the patients.

  7. INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY PERFLUORINATED COMPOUNDS IN RAT LIVER AND DOLPHIN KIDNEY EPITHELIAL CELL LINES IN VITRO AND SPRAGUE-DAWLEY RATS IN VIVO

    Science.gov (United States)

    Abstract Gap Junctional Intercellular Communication (GJIC) is the major pathway of intercellular signal transduction, and is, thus, important for normal cell growth and function. Recent studies have revealed a global distribution of some perfluorinated organic compounds e...

  8. Mast Cell Tryptase Reduces Junctional Adhesion Molecule-A (JAM-A) Expression in Intestinal Epithelial Cells: Implications for the Mechanisms of Barrier Dysfunction in Irritable Bowel Syndrome.

    LENUS (Irish Health Repository)

    Wilcz-Villega, Ewa M

    2013-07-01

    The objective of this study was to investigate how mast cell tryptase may influence intestinal permeability and tight junction (TJ) proteins in vitro and explore translation to irritable bowel syndrome (IBS).

  9. The significance of Epstein Barr Virus (EBV & DNA Topoisomerase II alpha (DNA-Topo II alpha immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED and Oral Squamous Cell Carcinoma (OSCC

    Directory of Open Access Journals (Sweden)

    Osman Mohamed M

    2008-11-01

    Full Text Available Abstract Background Head and neck cancer including oral cancer is considered to develop by accumulated genetic alterations and the major pathway is cancerization from lesions such as intraepithelial dysplasia in oral leukoplakia and erythroplakia. The relationship of proliferation markers with the grading of dysplasia is uncertain. The involvement of EBV in oral carcinogenesis is not fully understood. Aim The present study was designed to investigate the role of EBV and DNA Topoisomerase II∝ (DNA-Topo II∝ during oral carcinogenesis and to examine the prognostic significance of these protein expressions in OSCCs. Methods Using specific antibodies for EBV and DNA-Topo II∝, we examined protein expressions in archival lesion tissues from 16 patients with oral epithelial dysplasia, 22 oral squamous cell carcinoma and 20 normal oral mucosa by immunohistochemistry. Clinical information was obtained through the computerized retrospective database from the tumor registry. Results DNA-Topo II∝ was expressed in all examined specimens. Analysis of Variance ANOVA revealed highly significant difference (P 0.05 in inferior surface of tongue and in hard palatal tissues. Significant differences were observed between OEDs and NSE (P Conclusion EBV and DNA Topo II-αLI expression are possible indicators in oral carcinogenesis and may be valuable diagnostic and prognostic indices in oral carcinoma.

  10. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

    2017-11-01

    Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

  11. Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung.

    Science.gov (United States)

    Monica, Valentina; Ceppi, Paolo; Righi, Luisella; Tavaglione, Veronica; Volante, Marco; Pelosi, Giuseppe; Scagliotti, Giorgio V; Papotti, Mauro

    2009-05-01

    Lung cancer classification in small-cell and non-small-cell types was recently challenged by data on the differential efficacy of new cytotoxic agents in specific histotypes. An accurate histotype definition has therefore gained interest in both preoperative and surgical materials, but is a hard task especially in undifferentiated large-cell tumors lacking morphological signs of squamous or glandular differentiation. The responsiveness of these latter subtypes to new drugs apparently more selective for adenocarcinomas or squamous carcinomas is not fully understood, also due to the heterogeneity of diagnostic criteria for this tumor entity. Current immunohistochemical markers are not fully specific and new molecules are to be explored. On the basis of gene expression profiling data, reporting a remarkable differential expression of desmocollin-3 (a protein localized in desmosomal junctions of stratified epithelial) between adeno- and squamous cancers, we immunostained 62 cases of resected undifferentiated large-cell lung carcinomas for desmocollin-3 (and for TTF-1, p63 and mucin stain), to test its ability to identify a (residual) squamous phenotype, if present. Desmocollin-3 was expressed in almost half of the undifferentiated large-cell cancers and was mutually exclusive with TTF-1 (positive in 39%; the remaining 18 % of cases was double negative). Special large-cell carcinoma variants expressed desmocollin-3 in 6 of 6 basaloid, 7 of 12 clear-cell types, again mutually exclusive with TTF-1 expression. None of seven sarcomatoid carcinomas reacted for either marker. In 31 cytological samples diagnosed as 'non-small-cell lung carcinoma', desmocollin-3 was again mutually exclusive with TTF-1 and stained all squamous carcinomas, 1 of 19 adenocarcinoma only, and 50% of large-cell carcinoma (all histologically confirmed). This combined morphophenotypic approach may represent a valid adjunct (for both surgical and cytological samples) in the selection of patients with

  12. Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application

    Science.gov (United States)

    Pilarczyk, Götz; Nesnidal, Ines; Gunkel, Manuel; Bach, Margund; Bestvater, Felix; Hausmann, Michael

    2017-01-01

    In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin-1β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ-irradiation or alternatively neuregulin-1β application mobilized ErbB receptors in a nucleograde fashion—a process attenuated by trastuzumab antibody application. This was accompanied by increased receptor density, indicating packing into transport units. Factors mobilizing ErbB receptors also mobilized plasma membrane resident gap junction channels. The time course of ErbB receptor activation and gap junction mobilization recapitulates the time course of non-homologous end-joining DNA repair. We explain our findings under terms of DNA injury-induced membrane receptor tyrosine kinase activation and retrograde trafficking. In addition, we interpret the phenomenon of retrograde co-trafficking of gap junction connexons stimulated by ErbB receptor activation. PMID:28208769

  13. MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Wang, Xiao-Jing; Zhang, Bing; Chen, Hua

    2016-10-23

    BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (Ptissues was than in normal adjacent esophageal tissues (Ptissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

  14. Squamous cell carcinoma in a capybara (Hydrochoerus hydrochaeris).

    Science.gov (United States)

    Hamano, Takahisa; Terasawa, Fumio; Tachikawa, Yoshiharu; Murai, Atsuko; Mori, Takashi; El-Dakhly, Khaled; Sakai, Hiroki; Yanai, Tokuma

    2014-09-01

    A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desmoplastic reaction. Based on the pathological findings, the mass was diagnosed as a squamous cell carcinoma. This is the first study to report squamous cell carcinoma in a capybara.

  15. Claudin-4 Overexpression in Epithelial Ovarian Cancer Is Associated with Hypomethylation and Is a Potential Target for Modulation of Tight Junction Barrier Function Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin

    Directory of Open Access Journals (Sweden)

    Babak Litkouhi

    2007-04-01

    Full Text Available BACKGROUND: Claudin-4, a tight junction (TJ protein and receptor for the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE, is overexpressed in epithelial ovarian cancer (EOC. Previous research suggests DNA methylation is a mechanism for claudin-4 overexpression in cancer and that C-CPE acts as an absorption-enhancing agent in claudin-4expressing cells. We sought to correlate claudin-4 overexpression in EOC with clinical outcomes and TJ barrier function, investigate DNA methylation as a mechanism for overexpression, and evaluate the effect of C-CPE on the TJ. METHODS: Claudin-4 expression in EOC was quantified and correlated with clinical outcomes. Claudin-4 methylation status was determined, and claudin-4-negative cell lines were treated with a demethylating agent. Electric cell-substrate impedance sensing was used to calculate junctional (paracellular resistance (Rb in EOC cells after claudin-4 silencing and after C-CPE treatment. RESULTS: Claudin4 overexpression in EOC does not correlate with survival or other clinical endpoints and is associated with hypomethylation. Claudin-4 overexpression correlates with Rb and C-CPE treatment of EOC cells significantly decreased Rb in a dose- and claudin-4-dependent noncytotoxic manner. CONCLUSIONS: C-CPE treatment of EOC cells leads to altered TJ function. Further research is needed to determine the potential clinical applications of C-CPE in EOC drug delivery strategies.

  16. Inhibition of Akt activity induces the mesenchymal-to-epithelial reverting transition with restoring E-cadherin expression in KB and KOSCC-25B oral squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Hong Sam-Pyo

    2009-02-01

    Full Text Available Abstract Background The Akt/PKB family of kinases is frequently activated in human cancers, including oral squamous cell carcinoma (OSCC. Akt-induced epithelial-to-mesenchymal transition (EMT involves downregulation of E-cadherin, which appears to result from upregulation of the transcription repressor Snail. Recently, it was proposed that carcinoma cells, especially in metastatic sites, could acquire the mesenchymal-to-epithelial reverting transition (MErT in order to adapt the microenvironments and re-expression of E-cadherin be a critical indicator of MErT. However, the precise mechanism and biologic or clinical importance of the MErT in cancers have been little known. This study aimed to investigate whether Akt inhibition would restore the expression of E-cadherin and β-catenin, reduce that of Vimentin, and induce the MErT in OSCC cells with low or negative expression of E-cadherin. We also investigate whether inhibition of Akt activity would affect the E-cadherin repressors and signaling molecules like NF-κB, ERK, and p38. Methods We screened several OSCC cell lines in order to select suitable cell line models for inducing MErT, using immunoblotting and methylation specific-PCR. We examined whether Akt inhibitor phosphatidylinositol ether lipid analogues (PIA treatment would restore the expression of E-cadherin and β-catenin, reduce that of Vimentin, and induce the MErT in KB and KOSCC-25B cells using RT-PCR, immunoblotting, immunofluorescence analysis, and in vitro migration assay. We also investigated whether inhibition of Akt activity would affect the E-cadherin repressors, including Snail, Twist, and SIP-1/ZEB-2 and signaling molecules like NF-κB, ERK, JNK, and p38 using RT-PCR, immunoblotting, and immunofluorescence analysis. Results Of the 7 OSCC cell lines, KB and KOSCC-25B showed constitutively activated phosphorylated Akt and low or negative expression of E-cadherin. Inhibition of Akt activity by PIA decreased NF-κB signaling

  17. Squamous odontogenic tumor-like proliferation in a radicular cyst: A case report

    Science.gov (United States)

    Marco-Molina, Vicente; Gay-Escoda, Cosme

    2013-01-01

    The squamous odontogenic tumour is a rare benign neoplasm whose aetiology remains unknown. It usually appears in the jaw and its origin could be related to the ephitelial remnants of Malassez. Histologically comprises numerous islets of squamous, non-keratinized, well-differentiated and rounded epithelial cells a fibrous stroma without signs of atypical cells. There is a non-neoplastic lesion with the same histological pattern than the squamous odontogenic tumour. This entity is characterized by squamous odontogenic tumour proliferations isolated into the cyst wall of an odontogenic cyst. It is rare and has a benign behavior. It has been suggested that these epithelial proliferations could be the former expression of the neoplastic form. It is very important to carry out clinical and radiological controls periodically. So far it has not been documented any change towards a squamous odontogenic tumour nor toward malignancy in a squamous odontogenic tumour like proliferation. Key words:Radicular cyst, squamous odontogenic tumour. PMID:24455099

  18. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  19. Indigenous lactobacilli strains of food and human sources reverse enteropathogenic E. coli O26:H11-induced damage in intestinal epithelial cell lines: effect on redistribution of tight junction proteins.

    Science.gov (United States)

    Jariwala, Ruchi; Mandal, Hemanti; Bagchi, Tamishraha

    2017-09-01

    The aim of the study was to investigate the neutralizing effect of lactobacilli isolated from indigenous food and human sources on enteropathogenic Escherichia coli (EPEC) O26 : H11-induced epithelial barrier dysfunction in vitro. This was assessed by transepithelial electrical resistance (TEER) and permeability assays using intestinal cell lines, HT-29 and Caco-2. Furthermore, the expression and distribution of tight junction (TJ) proteins were analysed by qRT-PCR and immunofluorescence assay, respectively. The nine strains used in the study were from different species viz. Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus salivarius and Lactobacillus plantarum. All strains were able to reverse the decrease in TEER and corresponding increase in permeability across E. coli-infected monolayers. Maximum reversal was observed after 18 h [up to 93.8±2.0 % by L. rhamnosus GG followed by L. fermentum IIs11.2 (92.6±2.2 %) and L. plantarum GRI-2 (91.9±0.9 %)] of lactobacilli exposure following EPEC O26 : H11 infection. All strains were able to redistribute the TJ proteins to the cell periphery either partially or completely. Moreover, L. helveticus FA-7 was also able to significantly increase the mRNA expression of ZO-1 and claudin-1 (2.5-fold and 3.0-fold, respectively; PGRI-2 were good in all the aspects studied, and the other strains were good in some aspects. L. helveticus FA-7, L. fermentum FA-1 and L. plantarum GRI-2 can therefore be used for potential therapeutic purpose against intestinal epithelial dysfunction.

  20. Lateral junction dynamics lead the way out.

    Science.gov (United States)

    Behrndt, Martin; Heisenberg, Carl-Philipp

    2014-02-01

    Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical-lateral contractility at E-cadherin-based cell-cell junctions.

  1. Squamous Cell Carcinoma in a Capybara (Hydrochoerus hydrochaeris)

    OpenAIRE

    2014-01-01

    ABSTRACT A 4-year and 2-month-old male capybara (Hydrochoerus hydrochaeris) was diagnosed with squamous cell carcinoma on the buttocks after chronic recurrent dermatosis. The capybara was euthanized, examined by computed tomography and necropsied; the tumor was examined histologically. Computed tomography showed a dense soft tissue mass with indistinct borders at the buttocks. Histological examination of the tumor revealed islands of invasive squamous epithelial tumor cells with a severe desm...

  2. Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

    LENUS (Irish Health Repository)

    Beddy, P

    2012-02-01

    BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal\\/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal\\/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal\\/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal\\/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

  3. Mixed Squamous Cell and Glandular Papilloma of the Lung in a 64-Year-Old Woman

    OpenAIRE

    Yun, Ju Sik; Kim, Do Wan; Choi, Yoo Duk; Na, Kook Joo; Song, Sang Yun

    2014-01-01

    Mixed squamous cell and glandular papilloma of the lung is an extremely rare benign epithelial tumor showing a mixture of squamous and glandular epithelium. Here, we report a case of mixed squamous cell and glandular papilloma that presented as a solitary nodule in the left lower lobe of a 64-year-old woman. Chest computed tomography demonstrated a lobulated mass in the basal segment of the left lower lobe. The patient underwent a lobectomy under the suspicion of lung malignancy. The histopat...

  4. Gap Junctions

    Science.gov (United States)

    Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L.; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

    2013-01-01

    Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012. PMID:23723031

  5. Gap junctions.

    Science.gov (United States)

    Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

    2012-07-01

    Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1853-1872, 2012.

  6. Squamous metaplasia of the rete ovarii in a Zebu cow

    Directory of Open Access Journals (Sweden)

    Santos Renato

    2012-12-01

    Full Text Available Abstract Background Stratified keratinizing squamous epithelium in the ovary has been associated with the diagnosis of ovarian teratoma in cows. Recently, the diagnosis of “epidermoid cyst” has been proposed. A case of squamous metaplasia of the rete ovarii in a Zebu cow is described in this report. Case presentation A crossbreed Zebu cow had both ovaries enlarged with multiple cysts. Most cysts were lined by well differentiated keratinizing stratified squamous epithelium and filled with keratinized lamellar material. Some cysts were lined by an epithelial layer that ranged from single cuboidal, double cuboidal epithelium, stratified non keratinized epithelium, and areas of keratinizing stratified squamous epithelium. Single or double layered cuboidal epithelia of the cysts expressed low molecular weight cytokeratin 7, whose expression was absent in the keratinizing stratified squamous epithelia of same cysts. Conversely, high molecular weight cytokeratins 1, 5, 10, and 14 were strongly expressed by the keratinizing stratified epithelium. Conclusion Squamous metaplasia of the rete ovarii was diagnosed. Squamous metaplasia of the rete ovarii, may account for some of the previously described squamous lesions in the ovary, which may have been misinterpreted as teratoma or epidermoid cysts.

  7. Mixed squamous cell and glandular papilloma of the lung in a 64-year-old woman.

    Science.gov (United States)

    Yun, Ju Sik; Kim, Do Wan; Choi, Yoo Duk; Na, Kook Joo; Song, Sang Yun

    2014-02-01

    Mixed squamous cell and glandular papilloma of the lung is an extremely rare benign epithelial tumor showing a mixture of squamous and glandular epithelium. Here, we report a case of mixed squamous cell and glandular papilloma that presented as a solitary nodule in the left lower lobe of a 64-year-old woman. Chest computed tomography demonstrated a lobulated mass in the basal segment of the left lower lobe. The patient underwent a lobectomy under the suspicion of lung malignancy. The histopathological diagnosis was mixed squamous cell and glandular papilloma.

  8. Epithelial abnormalities of urinary bladder.

    Science.gov (United States)

    Mostofi, F K; Davis, C J

    1984-01-01

    We have called attention to certain epithelial lesions of the bladder characterized as proliferative, metaplastic, and neoplastic. In the first group are included hyperplasia, von Brunn's nests, papillary cystitis, papilloma and inverted papilloma. The second category includes squamous metaplasia, mucous metaplasia, and tubular metaplasia. These two categories, while benign, are indicative of agitated sick mucosa and may progress to neoplasia. The neoplastic changes consist of carcinoma involving the surface epithelium, von Brunn's nests, papillary cystitis, and/or cystitis cystica.

  9. Squamous cell carcinoma of the anal sac in five dogs.

    Science.gov (United States)

    Esplin, D G; Wilson, S R; Hullinger, G A

    2003-05-01

    Tumors of the perianal area of dogs are common and include multiple tumor types. Whereas perianal adenomas occur often, adenocarcinomas of the apocrine glands of the anal sac occur less frequently. A review of the literature revealed no reports of squamous cell carcinomas arising from the epithelial lining of the anal sac. Squamous cell carcinomas originating from the lining of the anal sac were diagnosed in five dogs. Microscopically, the tumors consisted of variably sized invasive nests and cords of epithelial cells displaying squamous differentiation. Four of the five dogs were euthanatized because of problems associated with local infiltration by the tumors. In the fifth dog, there was no evidence of tumor 7 months after surgical removal, but further follow up was not available.

  10. Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor.

    Science.gov (United States)

    Heikinheimo, K; Kurppa, K J; Laiho, A; Peltonen, S; Berdal, A; Bouattour, A; Ruhin, B; Catón, J; Thesleff, I; Leivo, I; Morgan, P R

    2015-01-01

    The aim of the study was to characterize the molecular relationship between ameloblastoma and keratocystic odontogenic tumor (KCOT) by means of a genome-wide expression analysis. Total RNA from 27 fresh tumor samples of 15 solid/multicystic intraosseous ameloblastomas and 12 sporadic KCOTs was hybridized on Affymetrix whole genome arrays. Hierarchical clustering separated ameloblastomas and KCOTs into 2 distinct groups. The gene set enrichment analysis based on 303 dental genes showed a similar separation of ameloblastomas and KCOTs. Early dental epithelial markers PITX2, MSX2, DLX2, RUNX1, and ISL1 were differentially overexpressed in ameloblastoma, indicating its dental identity. Also, PTHLH, a hormone involved in tooth eruption and invasive growth, was one of the most differentially upregulated genes in ameloblastoma. The most differentially overexpressed genes in KCOT were squamous epithelial differentiation markers SPRR1A, KRTDAP, and KRT4, as well as DSG1, a component of desmosomal cell-cell junctions. Additonally, the epithelial stem cell marker SOX2 was significantly upregulated in KCOT when compared with ameloblastoma. Taken together, the gene expression profile of ameloblastoma reflects differentiation from dental lamina toward the cap/bell stage of tooth development, as indicated by dental epithelium-specific transcription factors. In contrast, gene expression of KCOT indicates differentiation toward keratinocytes. © International & American Associations for Dental Research 2014.

  11. Cell culture model predicts human disease: Altered expression of junction proteins and matrix metalloproteinases in cervical dysplasia

    Directory of Open Access Journals (Sweden)

    Kivi Niina

    2012-08-01

    Full Text Available Abstract Background Cervical cancer is necessarily caused by human papillomaviruses, which encode three oncogenes manifesting their functions by interfering with a number of cellular proteins and pathways: the E5, E6, and E7 proteins. We have earlier found in our microarray studies that the E5 oncogene crucially affects the expression of cellular genes involved in adhesion and motility of epithelial cells. Methods In order to biologically validate our previous experimental findings we performed immunohistochemical staining of a representative set of tissue samples from different grades of high-risk human papillomavirus associated cervical disease as well as normal squamous and columnar cervical epithelium. Three-dimensional collagen raft cultures established from E5-expressing and control epithelial cells were also examined. The expression of p16, matrix metalloproteinase (MMP -7, MMP-16, cytokeratin (CK 8/18, laminin, E-cadherin and beta-catenin was studied. Results In agreement with our previous microarray studies, we found intense staining for E-cadherin and beta-catenin in adherens junctions even in high-grade cervical lesions. Staining for MMP-16 was increased in severe disease as well. No significant change in staining for MMP-7 and cytokeratin 8/18 along with the grade of cervical squamous epithelial disease was observed. Conclusions Here we have confirmed, using tissue material from human papillomavirus associated lesions, some of the cellular gene expression modifications that we earlier reported in an experimental system studying specifically the E5 oncogene of papillomaviruses. These findings were partially surprising in the context of cervical carcinogenesis and emphasize that the complexity of carcinogenesis is not yet fully understood. Microarray approaches provide a wide overwiev of gene expression in experimental settings, which may yield biologically valid biomarkers for disease diagnostics, prognosis, and follow-up.

  12. The role of Rap1 in cell-cell junction formation

    NARCIS (Netherlands)

    Kooistra, M.R.H.

    2008-01-01

    Both epithelial and endothelial cells form cell-cell junctions at the cell-cell contacts to maintain tissue integrity. Proper regulation of cell-cell junctions is required for the organisation of the tissue and to prevent leakage of blood vessels. In endothelial cells, the cell-cell junctions are

  13. Comparative Proteome Analysis of Human Lung Squamous Carcinoma Tissue

    Institute of Scientific and Technical Information of China (English)

    LI Cui; TANG Can'e; DUAN Chaojun; YI Hong; XIAO Zhiqiang; CHEN Zhuchu

    2006-01-01

    Objective: To establish the two-dimensional electrophoresis profiles with high resolution and reproducibility from human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue, and to identify differential expression tumor-associated proteins by using proteome analysis. Methods: Comparative proteome analysis with 20 human lung squamous carcinoma tissues and the paired normal bronchial epithelial tissues adjacent to tumors was carried out. The total proteins of human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE) and silver staining. The differential expression proteins were analyzed and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: (1) Well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained. For tumor tissue, average spots of 3 gels were 1567±46, and 1436±54 spots were matched with an average matching rate of 91.6%. For control, average spots of 3 gels were 1349±58, and 1228±35 spots were matched with an average matching rate of 91.03%. The average position deviation of matched spots was 0.924±0.128 mm in IEF direction, and 1.022±0.205 mm in SDS-PAGE direction; (2)A total of 1178±56 spots were matched between the electrophoretic maps of 20 human lung squamous carcinoma tissues and paired normal tumor-adjacent bronchial epithelial tissues. Seventy-six differentially expressed proteins were screened; (3) Sixty-eight differential proteins were identified by PMF, some proteins were the products of oncogenes, and others involved in the regulation of cell cycle and signal transduction;(4) In order to validate the reliability of the identified results, the expression of 3 proteins mdm2, c-jun and EGFR, which was correlated with lung

  14. HIV gp120 binds to mannose receptor on vaginal epithelial cells and induces production of matrix metalloproteinases.

    Directory of Open Access Journals (Sweden)

    Sashaina E Fanibunda

    Full Text Available BACKGROUND: During sexual transmission of HIV in women, the virus breaches the multi-layered CD4 negative stratified squamous epithelial barrier of the vagina, to infect the sub-epithelial CD4 positive immune cells. However the mechanisms by which HIV gains entry into the sub-epithelial zone is hitherto unknown. We have previously reported human mannose receptor (hMR as a CD4 independent receptor playing a role in HIV transmission on human spermatozoa. The current study was undertaken to investigate the expression of hMR in vaginal epithelial cells, its HIV gp120 binding potential, affinity constants and the induction of matrix metalloproteinases (MMPs downstream of HIV gp120 binding to hMR. PRINCIPAL FINDINGS: Human vaginal epithelial cells and the immortalized vaginal epithelial cell line Vk2/E6E7 were used in this study. hMR mRNA and protein were expressed in vaginal epithelial cells and cell line, with a molecular weight of 155 kDa. HIV gp120 bound to vaginal proteins with high affinity, (Kd = 1.2±0.2 nM for vaginal cells, 1.4±0.2 nM for cell line and the hMR antagonist mannan dose dependently inhibited this binding. Both HIV gp120 binding and hMR exhibited identical patterns of localization in the epithelial cells by immunofluorescence. HIV gp120 bound to immunopurified hMR and affinity constants were 2.9±0.4 nM and 3.2±0.6 nM for vaginal cells and Vk2/E6E7 cell line respectively. HIV gp120 induced an increase in MMP-9 mRNA expression and activity by zymography, which could be inhibited by an anti-hMR antibody. CONCLUSION: hMR expressed by vaginal epithelial cells has high affinity for HIV gp120 and this binding induces production of MMPs. We propose that the induction of MMPs in response to HIV gp120 may lead to degradation of tight junction proteins and the extracellular matrix proteins in the vaginal epithelium and basement membrane, leading to weakening of the epithelial barrier; thereby facilitating transport of HIV across the

  15. Two Canine Papillomaviruses Associated With Metastatic Squamous Cell Carcinoma in Two Related Basenji Dogs.

    Science.gov (United States)

    Luff, J; Rowland, P; Mader, M; Orr, C; Yuan, H

    2016-11-01

    Papillomaviruses (PV) are associated with benign mucosal and cutaneous epithelial proliferations. In dogs, PV-associated pigmented plaques and papillomas can undergo malignant transformation, but this is rare, and most cases of canine squamous cell carcinoma do not arise from PV-induced precursor lesions. We describe herein the progression of pigmented plaques to invasive and metastatic squamous cell carcinoma associated with 2 canine papillomaviruses (CPV) in 2 related Basenji dogs. Immunohistochemistry for PV antigen revealed strong nuclear immunoreactivity within keratinocytes from pigmented plaques from both dogs, consistent with a productive viral infection. Polymerase chain reaction (PCR) using degenerate primers for the L1 gene revealed PV DNA sequences from 2 different CPVs. In situ hybridization for CPV revealed strong hybridization signals within the pigmented plaques and neoplastic squamous epithelial cells from both dogs. We report here progression of PV-associated pigmented plaques to metastatic squamous cell carcinoma within 2 Basenji dogs associated with 2 different CPVs.

  16. Force transmission in epithelial tissues.

    Science.gov (United States)

    Vasquez, Claudia G; Martin, Adam C

    2016-03-01

    In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and structure and also provide signals that influence cells' decisions to divide, die, or differentiate. Forces are transmitted across epithelia because cells are mechanically linked through junctional complexes, and forces can propagate through the cell cytoplasm. Here, we review some of the molecular mechanisms responsible for force generation, with a specific focus on the actomyosin cortex and adherens junctions. We then discuss evidence for how these mechanisms promote cell shape changes and force transmission in tissues.

  17. MicroRNA profiling of cisplatin-resistant oral squamous cell carcinoma cell lines enriched with cancer-stem-cell-like and epithelial-mesenchymal transition-type features

    Science.gov (United States)

    Ghosh, Ruma Dey; Ghuwalewala, Sangeeta; Das, Pijush; Mandloi, Sapan; Alam, Sk Kayum; Chakraborty, Jayanta; Sarkar, Sajal; Chakrabarti, Saikat; Panda, Chinmoy Kumar; Roychoudhury, Susanta

    2016-01-01

    Oral cancer is of major public health problem in India. Current investigation was aimed to identify the specific deregulated miRNAs which are responsible for development of resistance phenotype through regulating their resistance related target gene expression in oral squamous cell carcinoma (OSCC). Cisplatin-resistant OSCC cell lines were developed from their parental human OSCC cell lines and subsequently characterised. The resistant cells exhibited enhanced proliferative, clonogenic capacity with significant up-regulation of P-glycoprotein (ABCB1), c-Myc, survivin, β-catenin and a putative cancer-stem-like signature with increased expression of CD44, whereas the loss of E-cadherin signifies induced EMT phenotype. A comparative analysis of miRNA expression profiling in parental and cisplatin-resistant OSCC cell lines for a selected sets (deregulated miRNAs in head and neck cancer) revealed resistance specific signature. Moreover, we observed similar expression pattern for these resistance specific signature miRNAs in neoadjuvant chemotherapy treated and recurrent tumours compared to those with newly diagnosed primary tumours in patients with OSCC. All these results revealed that these miRNAs play an important role in the development of cisplatin-resistance mainly through modulating cancer stem-cell-like and EMT-type properties in OSCC. PMID:27045798

  18. Endocytosis and Recycling of Tight Junction Proteins in Inflammation

    Directory of Open Access Journals (Sweden)

    Markus Utech

    2010-01-01

    Full Text Available A critical function of the epithelial lining is to form a barrier that separates luminal contents from the underlying interstitium. This barrier function is primarily regulated by the apical junctional complex (AJC consisting of tight junctions (TJs and adherens junctions (AJs and is compromised under inflammatory conditions. In intestinal epithelial cells, proinflammatory cytokines, for example, interferon-gamma (IFN-γ, induce internalization of TJ proteins by endocytosis. Endocytosed TJ proteins are passed into early and recycling endosomes, suggesting the involvement of recycling of internalized TJ proteins. This review summarizes mechanisms by which TJ proteins under inflammatory conditions are internalized in intestinal epithelial cells and point out comparable mechanism in nonintestinal epithelial cells.

  19. Trimodal spectroscopy as a tool for detecting cervical squamous intraepithelial lesions in vivo

    Science.gov (United States)

    Georgakoudi, Irene; Sheets, Ellen E.; Crum, Christopher P.; Mueller, Markus G.; Backman, Vadim; Feld, Michael S.

    2001-10-01

    Using intrinsic fluorescence, diffuse reflectance and light scattering spectroscopy we extracted quantitative biochemical and morphological information in vivo about the bulk tissue and the epithelial cell nuclei of ectocervical sites from 44 patients. Significant changes were observed in tissue morphology and biochemistry between normal, squamous metaplastic and squamous intraepithelial lesion (SIL) sites. The combined use of all three spectroscopic techniques (tri-modal spectroscopy) yielded superior results for detecting SILs than any one of the techniques alone.

  20. Squamous cell dysplasia and carcinoma of the conjunctiva

    DEFF Research Database (Denmark)

    Ramberg, Ingvild; Heegaard, Steffen; Prause, Jan Ulrik

    2015-01-01

    %) had epithelial dysplasia, 19 (13%) had carcinoma in situ, and 29 (20%) had squamous cell carcinoma. A significantly higher proportion of men were found. The median age at diagnosis was 65 years. The risk of recurrence was 10.0% [95% confidence interval (CI): 5.0–15.0] after 1 year and 17.2% (95% CI......Purpose To investigate the epidemiology of squamous cell dysplasia and carcinoma of the conjunctiva in Denmark. Methods Review of the histopathological case reports at the Eye Pathology Institute (EPI), University of Copenhagen, and the National Danish Pathology Bank from 1980 to 2011. Information......: 10.8–23.7) after 5 years. The lesions were most often localized to the corneal limbus. In our records, one patient had a lymph node metastasis and the disease necessitated enucleation in two patients. No patients had died from squamous cell carcinoma of the conjunctiva. Conclusion Overall, our data...

  1. Cytoskeletal changes induced by allosteric modulators of calcium-sensing receptor in esophageal epithelial cells.

    Science.gov (United States)

    Abdulnour-Nakhoul, Solange; Brown, Karen L; Rabon, Edd C; Al-Tawil, Youhanna; Islam, Mohammed T; Schmieg, John J; Nakhoul, Nazih L

    2015-11-01

    The calcium-sensing receptor (CaSR), a G-protein-coupled receptor, plays a role in glandular and fluid secretion in the gastrointestinal tract, and regulates differentiation and proliferation of epithelial cells. We examined the expression of CaSR in normal and pathological conditions of human esophagus and investigated the effect of a CaSR agonist, cinacalcet (CCT), and antagonist, calhex (CHX), on cell growth and cell-cell junctional proteins in primary cultures of porcine stratified squamous esophageal epithelium. We used immunohistochemistry and Western analysis to monitor expression of CaSR and cell-cell adhesion molecules, and MTT assay to monitor cell proliferation in cultured esophageal cells. CCT treatment significantly reduced proliferation, changed the cell shape from polygonal to spindle-like, and caused redistribution of E-cadherin and β-catenin from the cell membrane to the cytoplasm. Furthermore, it reduced expression of β-catenin by 35% (P < 0.02) and increased expression of a proteolysis cleavage fragment of E-cadherin, Ecad/CFT2, by 2.3 folds (P < 0.01). On the other hand, CHX treatment enhanced cell proliferation by 27% (P < 0.01), increased the expression of p120-catenin by 24% (P < 0.04), and of Rho, a GTPase involved in cytoskeleton remodeling, by 18% (P < 0.03). In conclusion, CaSR is expressed in normal esophagus as well as in Barrett's, esophageal adenocarcinoma, squamous cell carcinoma, and eosinophilic esophagitis. Long-term activation of CaSR with CCT disrupted the cadherin-catenin complex, induced cytoskeletal remodeling, actin fiber formation, and redistribution of CaSR to the nuclear area. These changes indicate a significant and complex role of CaSR in epithelial remodeling and barrier function of esophageal cells.

  2. Effect of the miR-886-5 p on the cervical squamous epithelial cell clone formation and cervical cancer chemotherapy%M iR-886-5 p对宫颈鳞状上皮细胞克隆形成和宫颈癌细胞化学药物治疗的影响

    Institute of Scientific and Technical Information of China (English)

    李晶华; 王明; 张瑞; 冯力民

    2015-01-01

    目的:探讨microRNA-886-5p(MiR-886-5p)对宫颈鳞状上皮细胞克隆形成及宫颈癌细胞化学药物治疗(以下简称化疗)的影响。方法应用基因芯片技术检测宫颈癌及其癌周组织microRNA的表达,筛选出MiR-886-5p在宫颈癌组织中高表达。生物信息系技术分析发现miRNA-886-5p靶向P53通路中多个基因的表达。用MiR-886-5p mimics和带有GFP标签的MiR-886-5p过表达载体稳定转染高危型人乳头瘤病毒(human papilomavirus,HPV16)阳性的永生化人宫颈鳞状上皮细胞H8细胞,应用Western blotting方法检测P53和P14的蛋白表达情况;应用平板克隆形成技术,观察对细胞克隆形成的影响。在宫颈癌SiHa细胞中,加入化疗药物紫杉醇和VP16后,应用real time RT-PCR技术,检测MiR-886-5p的表达情况。结果过表达 MiR-886-5p后,H8细胞的克隆形成率明显高于阴性对照组,并且降调P53通路中P14和P53蛋白的表达。加入化疗药紫杉醇和VP16后, SiHa细胞中MiR-886-5p表达明显升高。结论 MiR-886-5p与宫颈鳞状细胞增生相关,它降调P14和P53两种蛋白的表达,且与宫颈癌细胞化疗抵抗相关。%Objective To explore the effect of the miR-886-5p on the cervical squamous epithelial cell clone formation and cervical cancer chemotherapy.Methods Microassay was carried out for cervical squamous cell carcinoma tissues( CSCCs) and adjacent non-tumor tissues.One of them is miR-886-5p that overexpression in CSCCs.Bioinformatics analysis suggests that P53 pathway genes( Bax, P14, GADD45B and 14-3-3δ) are miR-886-5p target genes.With a GFP tag overexpression of miR-886-5p plasmid we evaluated the formation of cervical epithelial cell clone.Downstream target validation was performed for miR-886-5p.MiR-886-5p was validated by RT-PCR after chemotherapy in SiHa cell.Results Forced expression of one miRNA, miR-886-5p, overexpressed in CSCC tissues lowered expression of the protein P14 and

  3. In vivo photo-detection of chemically induced premalignant lesions and squamous cell carcinoma of the rat palatal mucosa

    NARCIS (Netherlands)

    Nauta, JM; Speelman, OC; vanLeengoed, HLLM; Nikkels, PGJ; Roodenburg, JLN; Witjes, MJH; Vermey, A

    1997-01-01

    Photo-detection using in vivo fluorescence was studied for different stages of chemically induced premalignant lesions and squamous cell carcinoma (SCC) of the Wistar rat palatal mucosa. It was found that the epithelial dysplasia (numerically expressed in the epithelial atypia index (EAI)) of the ra

  4. Prevalence of human papillomaviruses in the healthy oral mucosa of women with high-grade squamous intra-epithelial lesion and of their partners as compared to healthy controls.

    Science.gov (United States)

    Tatár, Tímea Zsófia; Kis, Andrea; Szabó, Éva; Czompa, Levente; Boda, Róbert; Tar, Ildikó; Szarka, Krisztina

    2015-10-01

    Oral human papillomavirus (HPV) carriage rates were investigated in relation to genital HPV carriage in women with HPV-associated cervical lesions and male partner of such women, including several couples, in comparison with healthy individuals. Buccal and lingual mucosa of 60 males and 149 females with healthy oral mucosa and without known genital lesion, genital and oral mucosa of further 40 females with cervical high-grade squamous intraepithelial lesion (HSIL) and 34 male sexual partners of women with HSIL (including 20 couples) were sampled. HPV DNA was detected using MY/GP PCR. Genotype was determined by sequencing or restriction fragment length polymorphism. Virus copy numbers were determined by real-time PCR. Overall, oral HPV carriage rate was 5.7% (12/209) in healthy individuals; average copy number was 5.8 × 10(2) copies/1 μg DNA; male and female rates were comparable. Oral carriage in women with HSIL was significantly higher, 20.0% (8/40, P = 0.003); males with partners with HSIL showed a carriage rate of 17.6% (6/34), copy numbers were similar to the healthy controls. In contrast, genital carriage rate (52.9%, 18/34 vs. 82.5%, 33/40; P = 0.006) and average copy number were lower in males (5.0 × 10(5) vs. 7.8 × 10(5) copies/1 μg DNA; P = 0.01). Oral copy numbers in these groups and in healthy individuals were comparable. High-risk genotypes were dominant; couples usually had the same genotype in the genital sample. In conclusion, genital HPV carriage is a risk factor of oral carriage for the individual or for the sexual partner, but alone is not sufficient to produce an oral HPV infection in most cases.

  5. Commensal bacteria modulate innate immune responses of vaginal epithelial cell multilayer cultures.

    Science.gov (United States)

    Rose, William A; McGowin, Chris L; Spagnuolo, Rae Ann; Eaves-Pyles, Tonyia D; Popov, Vsevolod L; Pyles, Richard B

    2012-01-01

    The human vaginal microbiome plays a critical but poorly defined role in reproductive health. Vaginal microbiome alterations are associated with increased susceptibility to sexually-transmitted infections (STI) possibly due to related changes in innate defense responses from epithelial cells. Study of the impact of commensal bacteria on the vaginal mucosal surface has been hindered by current vaginal epithelial cell (VEC) culture systems that lack an appropriate interface between the apical surface of stratified squamous epithelium and the air-filled vaginal lumen. Therefore we developed a reproducible multilayer VEC culture system with an apical (luminal) air-interface that supported colonization with selected commensal bacteria. Multilayer VEC developed tight-junctions and other hallmarks of the vaginal mucosa including predictable proinflammatory cytokine secretion following TLR stimulation. Colonization of multilayers by common vaginal commensals including Lactobacillus crispatus, L. jensenii, and L. rhamnosus led to intimate associations with the VEC exclusively on the apical surface. Vaginal commensals did not trigger cytokine secretion but Staphylococcus epidermidis, a skin commensal, was inflammatory. Lactobacilli reduced cytokine secretion in an isolate-specific fashion following TLR stimulation. This tempering of inflammation offers a potential explanation for increased susceptibility to STI in the absence of common commensals and has implications for testing of potential STI preventatives.

  6. Commensal Bacteria Modulate Innate Immune Responses of Vaginal Epithelial Cell Multilayer Cultures

    Science.gov (United States)

    Rose, William A.; McGowin, Chris L.; Spagnuolo, Rae Ann; Eaves-Pyles, Tonyia D.; Popov, Vsevolod L.; Pyles, Richard B.

    2012-01-01

    The human vaginal microbiome plays a critical but poorly defined role in reproductive health. Vaginal microbiome alterations are associated with increased susceptibility to sexually-transmitted infections (STI) possibly due to related changes in innate defense responses from epithelial cells. Study of the impact of commensal bacteria on the vaginal mucosal surface has been hindered by current vaginal epithelial cell (VEC) culture systems that lack an appropriate interface between the apical surface of stratified squamous epithelium and the air-filled vaginal lumen. Therefore we developed a reproducible multilayer VEC culture system with an apical (luminal) air-interface that supported colonization with selected commensal bacteria. Multilayer VEC developed tight-junctions and other hallmarks of the vaginal mucosa including predictable proinflammatory cytokine secretion following TLR stimulation. Colonization of multilayers by common vaginal commensals including Lactobacillus crispatus, L. jensenii, and L. rhamnosus led to intimate associations with the VEC exclusively on the apical surface. Vaginal commensals did not trigger cytokine secretion but Staphylococcus epidermidis, a skin commensal, was inflammatory. Lactobacilli reduced cytokine secretion in an isolate-specific fashion following TLR stimulation. This tempering of inflammation offers a potential explanation for increased susceptibility to STI in the absence of common commensals and has implications for testing of potential STI preventatives. PMID:22412914

  7. Subungual squamous cell carcinoma*

    Science.gov (United States)

    Padilha, Carolina Barbosa de Sousa; Balassiano, Laila Klotz de Almeida; Pinto, Julyana Calegari; de Souza, Flávia Crespo Schueler; Kac, Bernard Kawa; Treu, Curt Mafra

    2016-01-01

    Although subungual squamous cell carcinoma is rare, it is the most common primary malignant neoplasms in this location. The higher incidence occurs in the fingernails, but involvement of the toenails is also possible. Subungual squamous cell carcinoma often looks like other more common benign lesions, such as fungal infection, onychomycosis, or viral wart. These factors, together with a general lack of awareness of this disease among physicians, often result in delayed diagnosis. Therefore, it is underdiagnosed, with few reports in the literature. The authors present a case of a man with a diagnosis of subungual squamous cell carcinoma in the hallux, without bone involvement, which was submitted to the appropriate surgical treatment. PMID:28099608

  8. A novel role for p115RhoGEF in regulation of epithelial plasticity.

    Science.gov (United States)

    Kher, Swapnil S; Struckhoff, Amanda P; Alberts, Arthur S; Worthylake, Rebecca A

    2014-01-01

    Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of junctions is associated with acquisition of mesenchymal features, such as enhanced protrusion and migration. Although Rho has been implicated in regulation of junctions in epithelial cells, the role of Rho signaling in the regulation of epithelial plasticity has not been understood. We show that members of the RGS RhoGEFs family play a critical role in regulation of epithelial cell-cell junctions in breast epithelial cells. We identify a novel role for p115RhoGEF in regulation of epithelial plasticity. Loss of p115RhoGEF leads to decreased junctional E-cadherin and enhanced protrusiveness and migration. Conversely, overexpression of p115RhoGEF enhanced junctional E-cadherin and inhibited cell protrusion and migration. siRNA screen of 23 Rho effectors showed that members of the Diaphanous-Related Formin (DRF) family are required for p115RhoGEF-mediated changes in epithelial plasticity. Thus, our data indicates a novel role for p115RhoGEF in regulation of epithelial plasticity, which is dependent on Rho-DRF signaling module.

  9. A novel role for p115RhoGEF in regulation of epithelial plasticity.

    Directory of Open Access Journals (Sweden)

    Swapnil S Kher

    Full Text Available Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of junctions is associated with acquisition of mesenchymal features, such as enhanced protrusion and migration. Although Rho has been implicated in regulation of junctions in epithelial cells, the role of Rho signaling in the regulation of epithelial plasticity has not been understood. We show that members of the RGS RhoGEFs family play a critical role in regulation of epithelial cell-cell junctions in breast epithelial cells. We identify a novel role for p115RhoGEF in regulation of epithelial plasticity. Loss of p115RhoGEF leads to decreased junctional E-cadherin and enhanced protrusiveness and migration. Conversely, overexpression of p115RhoGEF enhanced junctional E-cadherin and inhibited cell protrusion and migration. siRNA screen of 23 Rho effectors showed that members of the Diaphanous-Related Formin (DRF family are required for p115RhoGEF-mediated changes in epithelial plasticity. Thus, our data indicates a novel role for p115RhoGEF in regulation of epithelial plasticity, which is dependent on Rho-DRF signaling module.

  10. Regulation of Tight Junctions in Upper Airway Epithelium

    Directory of Open Access Journals (Sweden)

    Takashi Kojima

    2013-01-01

    Full Text Available The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP, which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

  11. Quantitative analysis of epithelial cells in urine from men with and without urethritis: implications for studying epithelial: pathogen interactions in vivo

    Directory of Open Access Journals (Sweden)

    Whittington Kate

    2009-07-01

    Full Text Available Abstract Background Epithelial cells in first catch urine (FCU specimens from 87 men with and without urethritis were quantified. Epithelial cells were broadly categorised into transitional and squamous populations using morphological characteristics and immunostaining with anti-pan leukocyte and anti-cytokeratin monoclonal antibodies. Findings The majority (77/87 = 89% of samples contained both transitional (76/87 = 87%; range 1 × 104 – 6 × 105, median 6 × 104 and squamous (57/87 = 66%; range 1 × 104 – 8 × 105, median 2 × 104 epithelial cells. The number of transitional cells correlated with the number of squamous cells (Spearman's rho = 0.697 p Conclusion Further studies are required to explore the complexity of epithelial cell populations in urine. These would provide novel opportunities for studying cellular interactions of C. trachomatis in male urethral infections, about which little is currently known.

  12. Epithelial-mesenchymal transition and the role of Snail, Slug and Twist in the carcinogenesis and development of oral squamous cell carcinoma%上皮-间充质转分化与转录因子Snail、Slug、Twist在口腔鳞状细胞癌发生、发展中的作用

    Institute of Scientific and Technical Information of China (English)

    阿里木江·吾守; 潘红芽; 张志愿

    2011-01-01

    Epithelial -mesenchymal transition (EMT) refers to critical events mostly observed in normal morphological development and during tumor progression, including invasion and metastasis, by which cancer cells acquire a fibroblast-like phenotype. Molecules involved in this process, such as Snail, Slug, and Twist have recently been demonstrated to be important for cancer cells to down-regulate epithelial markers and up-regulate mesenchymal markers in order to become motile and invasive. Disappearance of E-cadherin is a milestone for EMT, found both in carcinomas and in some fibrotic diseases. As a regulator, Snail, Slug, and Twist induce EMT by repressing E-cadherin expression and facilitate migration and invasion of carcinoma. Snail, Slug and Twist contributes to the development of oral squamous cell carcinoma (OSCC), especially correlates positively with invasiveness and metastasis of OSCC.The aim of this paper is to introduce EMT and Snail, Slug, Twist in aspect of regulation,construction features,and bionomics,and carry out a bibliographic review on its role in OSCC.Supported by National Natural Science Foundation of China (30630065).%上皮-间充质转分化(EMT)是上皮细胞在特定生理和病理情况下向间充质细胞转化的现象,它在上皮性肿瘤的演进中发挥了关键作用.肿瘤发生过程中,转录因子Snail、Slug、Twist等常可引发EMT,促使肿瘤的侵袭与转移.Snail、Slug和Twist在口腔鳞癌演变过程中,尤其在浸润和转移中发挥重要作用.该文介绍EMT的概念、特征以及Snail、Slug和Twist的基因结构特点、生物学特性等,特别对其在口腔鳞癌中的作用进行了综述.

  13. Polarized sorting and trafficking in epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Xinwang Cao; Michal A Surma; Kai Simons

    2012-01-01

    The polarized distribution of proteins and lipids at the surface membrane of epithelial cells results in the formation of an apical and a basolateral domain,which are separated by tight junctions.The generation and maintenance of epithelial polarity require elaborate mechanisms that guarantee correct sorting and vectorial delivery of cargo molecules.This dynamic process involves the interaction of sorting signals with sorting machineries and the formation of transport carriers.Here we review the recent advances in the field of polarized sorting in epithelial cells.We especially highlight the role of lipid rafts in apical sorting.

  14. [Immunohistochemical study of dysplasia and squamous cell carcinoma of the larynx].

    Science.gov (United States)

    Nishiya, M

    1989-01-01

    Formalin- or alcohol-fixed, paraffin-embedded laryngeal specimens were stained immunohistochemically with several kinds of monoclonal anti-Keratin antibody (KL-1, PKK-1, PKK-2, PKK-3), polyclonal anti-Keratin antibody, and epithelial membrane antigen. Immunohistochemical technique was used by Avidin-Biotin Complex method with the following subjects; normal epithelium 6 cases, dysplasia 15 cases, inflammation and polyp 12 cases, squamous cell carcinoma 47 cases. 6 specimens of squamous cell carcinoma were totally resected and alcohol-fixed, and other specimens were all biopsied and formalin-fixed. Comparing these two methods, the alcohol-fixed specimen gave superior result to those obtained with formalin-fixed in its staining. Non-staining area was recognized around basal layer by KL-1 stain in the normal epithelium. Enlargement of non-staining area was recognized in the dysplasia. Also, KL-1 staining showed positive staining with the keratinizing squamous cell carcinoma, and weak staining with the non-keratinizing squamous cell carcinoma. And, PKK-3 showed weak staining in the keratinizing squamous cell carcinoma. The results indicate that high molecular weight keratin (56 kilodalton) hardly localize around the basal layer in the squamous epithelium, and also in the non-keratinizing squamous cell carcinoma. The other way, this also suggests that low molecular weight keratin (45 kilodalton) hardly localize in the keratinizing squamous cell carcinoma. It is supposed that intracellular localization of keratin of dysplastic epithelium and squamous cell carcinoma varies from that in the normal squamous epithelium. Accordingly, monoclonal keratin stain is thought to be an useful method for the diagnosis of dysplasia and squamous cell carcinoma.

  15. Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy.

    Science.gov (United States)

    Herfs, Michael; Hubert, Pascale; Poirrier, Anne-Lise; Vandevenne, Patricia; Renoux, Virginie; Habraken, Yvette; Cataldo, Didier; Boniver, Jacques; Delvenne, Philippe

    2012-07-01

    Tracheobronchial squamous metaplasia is common in smokers, and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Although this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia remains unclear. In the present study, we investigated the implication of cigarette smoke-mediated proinflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. Using immunohistological techniques, we showed a higher epithelial expression of TNF-α, IL-1β, and IL-6, as well as an activation of NF-κB and activator protein-1/mitogen-activated protein kinase signaling pathways in the respiratory tract of smoking patients, compared with the normal ciliated epithelium of nonsmoking patients. In addition, we demonstrated that these signaling pathways strongly influence the proliferation and differentiation state of in vitro-generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks, and demonstrated that anti-TNF-α (etanercept), anti-IL-1β (anakinra), and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and the development of squamous metaplasia. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, the administration of proinflammatory cytokine antagonists may have clinical applications in the management of patients with COPD.

  16. Lipid polarity and sorting in epithelial cells

    NARCIS (Netherlands)

    van Meer, G.; Simons, K.

    1988-01-01

    Apical and basolateral membrane domains of epithelial cell plasma membranes possess unique lipid compositions. The tight junction, the structure separating the two domains, forms a diffusion barrier for membrane components and thereby prevents intermixing of the two sets of lipids. The barrier appar

  17. Renal Pelviceal Keratinizing Squamous Metaplasia with Sparing of Pyramidal Zones

    Directory of Open Access Journals (Sweden)

    Richard H. Siderits

    2012-01-01

    Full Text Available Metaplastic changes in the urothelium of the upper urinary tract are relatively infrequent. Metaplasia may present as either squamous or less often glandular differentiation. The process may be associated with chronic inflammation or associated chronic infections. There may be malignant transformation to either squamous cell carcinoma or adenocarcinoma. The demarcation of the metaplastic process in the minor calyces has not been well documented to date. We report the case of a 74-year-old female patient who presented with a history of chronic renal disease and acute pyohydronephrosis. The patient underwent a nephroureterectomy which revealed keratinizing desquamative squamous metaplasia throughout the renal pelvis and upper urinary tract with abrupt termination of metaplasia at the junction of the renal pelvis and the minor calyx (pyramidal zone. Immunohistochemical evaluation documents metaplastic urothelium stained positive for CK5, before converting sharply to simple cuboidal epithelium in the minor calyx (pyramidal zones which stained positive CK7. At the junction of the metaplastic components and low cuboidal lined minor calyceal surfaces, the underlying stroma showed loss of ureteral muscularis mucosa with transition to renal parenchymal type stroma. We believe that this observation is unique and potentially relevant to the etiology and pathophysiology of pelviceal metaplasia.

  18. LICHEN PLANUS WITH ASSOSIATED SQUAMOUS CELL CARCINOMA IN THE ORAL MUCOSA

    Directory of Open Access Journals (Sweden)

    Valluvan

    2014-06-01

    Full Text Available Lichen means dry scurfy forms of lower plant life and the same name indicate dry skin disorder like lichen planus. The basic histological feature of lichen planus is basal layer damage and inflammatory reaction in the sub epithelial zone. There are several sub types 0.5% of mucosal lichen planus can become or harbor invasive squamous cell carcinoma

  19. Human neutrophil defensins and secretory leukocyte proteinase inhibitor in squamous metaplastic epithelium of bronchial airways.

    NARCIS (Netherlands)

    Aarbiou, J.; Schadewijk, A. van; Stolk, J.; Sont, J.K.; Boer, W.I.; Rabe, K.F.; Krieken, J.H.J.M. van; Mauad, T.; Hiemstra, P.S.

    2004-01-01

    OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the num

  20. Drosophila PATJ supports adherens junction stability by modulating Myosin light chain activity

    National Research Council Canada - National Science Library

    Sen, Arnab; Nagy-Zsvér-Vadas, Zsanett; Krahn, Michael P

    2012-01-01

    ... (Pals1-associated tight junction protein) was not per se crucial for the maintenance of apical-basal polarity in Drosophila melanogaster epithelial cells but rather regulated Myosin localization and phosphorylation...

  1. Expressions of 8-OHdGa nd phospho-epithelial growth factor receptor in tongue squamous cell carcinoma and their correlation%8-OHdG 与 p-EGFR 在舌鳞癌中的表达及两者的相关性

    Institute of Scientific and Technical Information of China (English)

    覃向明; 陈蕾; 于大海; 梁飞新

    2016-01-01

    Objective To detect the expressions of 8-hydroxydeoxyguanine(8-OhdG) and phospho-epithelial growth factor receptor ( p-EGFR) in tongue squamous cell carcinoma ( TSCC) and their correlation .Methods The ex-pressions of 8-OHdG and p-EGFR in 30 specimens of tongue squamous cell carcinoma tissues and adjacent -carcinoma tissues were detected by immunohistochemistry .The correlation between 8-OHdG expression and p-EGFR expression was analyzed by Spearman rank correlation analysis .Results Both 8-OHdG and p-EGFR were highly expressed in the TSCC tissues, and their positive rates were 80.0%, 56.7%respectively, whereas the low expressions which were shown with positive rate of 16.7%, 6.7% respectively , were observed in the adjacent-carcinoma tissues .The ex-pressions of 8-OHdG and p-EGFR in carcinoma tissue were significantly higher than those in the adjacent-carcinoma tissue(P<0.05), and the statistically significant correlation was observed between 8-OHdG expression and p-EGFR expression ( P<0.05 ) .Conclusion Reactive oxygen species express in oral cancer , which is positively correlated to p-EGFR.%目的探讨舌鳞状细胞癌组织中活性氧的标志物8-羟基脱氧鸟苷(8-OHdG )和磷酸化表皮生长因子受体( p-EGFR)的表达水平,并分析二者的相互关系。方法应用免疫组化法检测30例舌鳞癌组织及其癌旁组织中8-OHdG和p-EGFR表达,通过相关性分析探讨两者之间的关系。结果8-OHdG和p-EGFR在舌癌组织中高表达,阳性表达率分别为80.0%、56.7%;两者在癌旁组织中呈低表达,阳性表达率分别为16.7%、6.7%,它们在癌组织中的阳性表达率均显著高于癌旁组织( P<0.05),8-OHdG的表达与p-EGFR的表达具有显著相关性( P<0.05)。结论该研究初步确定活性氧在口腔癌中的表达和作用,以及其与磷酸化EGFR的正相关性。

  2. Small vulvar squamous cell carcinomas and adjacent tissues. A morphologic study

    DEFF Research Database (Denmark)

    Poulsen, Hemming; Junge, Jette; Vyberg, Mogens;

    2003-01-01

    Vulvar squamous cell carcinomas are of different subtypes and degrees of differentiation, and may be associated with adjacent lichen sclerosus and/or varying degrees of dysplasia. The aim of this investigation was to study small carcinomas with a diameter of less than 2 cm in order to find...... a possible relation between subtypes of carcinomas and adjacent epithelial changes. Fourteen cases of small vulvar squamous cell carcinomas were totally embedded in paraffin. Serial sectioning made a detailed mapping of all different lesions possible, and a two- and three-dimensional imaging was obtained...... in each case. Seven patients with keratinizing squamous cell carcinomas (median age 65) had adjacent lichen sclerosus. All carcinomas were completely surrounded by areas of VIN1. VIN2 and VIN3 were not found. Seven patients without lichen sclerosus (median age 58) showed squamous cell carcinomas...

  3. Molecular electronic junction transport

    DEFF Research Database (Denmark)

    Solomon, Gemma C.; Herrmann, Carmen; Ratner, Mark

    2012-01-01

    Whenasinglemolecule,oracollectionofmolecules,isplacedbetween two electrodes and voltage is applied, one has a molecular transport junction. We discuss such junctions, their properties, their description, and some of their applications. The discussion is qualitative rather than quantitative, and f...

  4. Squamous cell carcinoma in equine prepuce with vertebral invasion

    Directory of Open Access Journals (Sweden)

    Marcelo George Mungai Chacur

    2014-06-01

    Full Text Available The squamous cell carcinoma is a malignant tumor that originates in the epidermal layer skin from the differentiation of keratinocytes. It has high incidence in dogs, cats, horses and cattle. Horses often occur in mucocutaneous junctions, areas like penis and foreskin are the most affected. The incidence is higher in castrated equines with more than 16 years old. This case describes a castrated crossbred horse, actually with 7 years old. The animal presented a mass in foreskin region with evolution of three months. Diagnosed as squamous cell carcinoma by aspirative cytology and biopsy. Surgical tumor mass excision was chosen as treatment. Two months after surgery there was local recurrence of tumor. Euthanasia was performed and a necropsy later in which was found the tumor invaded the adjacent musculature extending from the spine in sacral region between vertebres S1 and S2.

  5. The effect of tumor metastasis associated gene 1 on the process of epithelial-mesenchymal transition in esophageal squamous cell carcinoma%肿瘤转移相关基因1在食管癌细胞上皮间质转化过程中的促进作用

    Institute of Scientific and Technical Information of China (English)

    刘欢; 王海娟; 李春晓; 李慧; 林晨; 钱海利

    2015-01-01

    目的 探讨肿瘤转移相关基因1(MTA1)对食管癌细胞上皮间质化(EMT)过程的影响及分子机制.方法 采用慢病毒感染方法建立MTA1敲降的食管癌细胞系LV3-shMTA1-KYSE410及MTA1过表达的食管癌细胞系LV5-MTA1-KYSE450;通过Western Blot方法检测上述食管癌细胞系中MTA1蛋白及EMT相关蛋白的表达水平;进而采用免疫荧光实验检测上述食管癌细胞系中EMT相关蛋白分子标志物E-cadherin和Vimentin的定位以及表达水平的变化;最后应用划痕实验明确MTA1表达水平改变后对食管癌细胞迁移能力的影响.结果 食管癌KYSE450细胞系过表达MTA1后,EMT相关蛋白标志物中的E-cadherin表达水平降低而Vimentin表达水平升高,迁移能力增强,细胞迁移率为0.91±0.00,对照组为0.23±0.04;食管癌KYSE410细胞系敲降MTA1后,E-cadherin表达水平升高而Vimentin 表达水平降低,迁移能力降低,细胞迁移率为0.19±0.01,对照组为0.53±0.01,差异均有统计学意义(P均<0.05).结论 MTA1过表达可促进食管癌细胞的间质化、提高食管癌细胞的迁移能力.%Objective To explore the effect and mechanism of metastasis associated gene 1 (MTA1) on epithelial-mesenchymal transition(EMT) of esophageal squamous cell carcinoma(ESCC).Methods Lentivirus infection method was used to establish the MTA1 knocking out cell line (LV3-shMTA1-KYSE410) and the MTA1 overexpressing cell line (LVS-MTA1-KYSE450).Western Blot was used to measure the expression of MTA1 and the proteins associated with EMT process.Furthermore,the expression and localization of E-cadherin and Vimentin were observed by immunofluorescence assay under confocal microscope.Finally,the wound healing method was performed to confirm the changes of migration ability of the established cell lines.Results When KYSE-450 cells were overexpressed MTA1,the expression level of E-cadherin was down-regulated while Vimentin was up-regulated,and the migration ability was enhanced (0

  6. Squamous cell carcinoma.

    Science.gov (United States)

    Webb, Julie L; Burns, Rachel E; Brown, Holly M; LeRoy, Bruce E; Kosarek, Carrie E

    2009-03-01

    Squamous cell carcinoma (SCC) is a relatively common, malignant neoplasm of dogs and cats that can arise in a variety of locations. The gross appearance of SCC can be variable and nonspecific, so definitive diagnosis requires microscopic examination of the tissue (cytology or histology). Several treatment modalities exist, but surgical excision, if possible, is regarded as the best treatment option. Early diagnosis and treatment of SCC are key because small, early-stage tumors are the most amenable to treatment and carry the best prognosis.

  7. Penis squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  8. Anal squamous intraepithelial neoplasia.

    Science.gov (United States)

    Bejarano, Pablo A; Boutros, Marylise; Berho, Mariana

    2013-12-01

    Diagnosis, follow up, and treatment of anal intraepithelial neoplasia are complex and not standardized. This may be partly caused by poor communication of biopsy and cytology findings between pathologists and clinicians as a result of a disparate and confusing terminology used to classify these lesions. This article focuses on general aspects of epidemiology and on clarifying the current terminology of intraepithelial squamous neoplasia, its relationship with human papilloma virus infection, and the current methods that exist to diagnose and treat this condition. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. A Case of Squamous Cell Carcinoma of the Renal Pelvis in association with Schistosoma hematobium

    Directory of Open Access Journals (Sweden)

    Muhammad A. A. Khan

    2012-01-01

    Full Text Available A 72-year-old man presented with painless frank haematuria. Investigations included intravenous urogram and abdominal/pelvic CT which revealed a marked focal thickening of the wall of the inferior aspect of the left renal pelvis extending into the lower pole calyx and into the pelviureteric junction resulting in left hydronephrosis. Urine cytology demonstrated clusters of malignant keratinised squamous cells and schistosome ova. He underwent left laparoscopic radical nephroureterectomy and histology revealed moderately differentiated keratinising squamous cell carcinoma in the renal pelvis.

  10. KLF4 transcriptionally activates non-canonical WNT5A to control epithelial stratification.

    Science.gov (United States)

    Tetreault, Marie-Pier; Weinblatt, Daniel; Shaverdashvili, Khvaramze; Yang, Yizeng; Katz, Jonathan P

    2016-05-17

    Epithelial differentiation and stratification are essential for normal homeostasis, and disruption of these processes leads to both injury and cancer. The zinc-finger transciption factor KLF4 is a key driver of epithelial differentiation, yet the mechanisms and targets by which KLF4 controls differentiation are not well understood. Here, we define WNT5A, a non-canonical Wnt ligand implicated in epithelial differentiation, repair, and cancer, as a direct transcriptional target that is activated by KLF4 in squamous epithelial cells. Further, we demonstrate functionally that WNT5A mediates KLF4 control of epithelial differentiation and stratification, as treatment of keratinocytes with WNT5A rescues defective epithelial stratification resulting from KLF4 loss. Finally, we show that the small GTPase CDC42 is regulated by KLF4 in a WNT5A dependent manner. As such, we delineate a novel pathway for epithelial differentiation and stratification and define potential therapeutic targets for epithelial diseases.

  11. Epithelial histogenesis during tooth development.

    Science.gov (United States)

    Lesot, H; Brook, A H

    2009-12-01

    This paper reviews the current understanding of the progressive changes mediating dental epithelial histogenesis as a basis for future collaborative studies. Tooth development involves morphogenesis, epithelial histogenesis and cell differentiation. The consecutive morphological stages of lamina, bud, cap and bell are also characterized by changes in epithelial histogenesis. Differential cell proliferation rates, apoptosis, and alterations in adhesion and shape lead to the positioning of groups of cells with different functions. During tooth histo-morphogenesis changes occur in basement membrane composition, expression of signalling molecules and the localization of cell surface components. Cell positional identity may be related to cell history. Another important parameter is cell plasticity. Independently of signalling molecules, which play a major role in inducing or modulating specific steps, cell-cell and cell-matrix interactions regulate the plasticity/rigidity of particular domains of the enamel organ. This involves specifying in space the differential growth and influences the progressive tooth morphogenesis by shaping the epithelial-mesenchymal junction. Deposition of a mineralized matrix determines the final shape of the crown. All data reviewed in this paper were investigated in the mouse.

  12. Occludin S471 Phosphorylation Contributes to Epithelial Monolayer Maturation.

    Science.gov (United States)

    Bolinger, Mark T; Ramshekar, Aniket; Waldschmidt, Helen V; Larsen, Scott D; Bewley, Maria C; Flanagan, John M; Antonetti, David A

    2016-08-01

    Multiple organ systems require epithelial barriers for normal function, and barrier loss is a hallmark of diseases ranging from inflammation to epithelial cancers. However, the molecular processes regulating epithelial barrier maturation are not fully elucidated. After contact, epithelial cells undergo size-reductive proliferation and differentiate, creating a dense, highly ordered monolayer with high resistance barriers. We provide evidence that the tight junction protein occludin contributes to the regulation of epithelial cell maturation upon phosphorylation of S471 in its coiled-coil domain. Overexpression of a phosphoinhibitory occludin S471A mutant prevents size-reductive proliferation and subsequent tight junction maturation in a dominant manner. Inhibition of cell proliferation in cell-contacted but immature monolayers recapitulated this phenotype. A kinase screen identified G-protein-coupled receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithelial packing and junction maturation. We conclude that occludin contributes to the regulation of size-reductive proliferation and epithelial cell maturation in a phosphorylation-dependent manner. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. Retinal pigment epithelial fine structure in the red-backed salamander (Plethodon cinereus).

    Science.gov (United States)

    Braekevelt, C R

    1992-07-01

    The retinal pigment epithelium (RPE) of the red-backed salamander (Plethodon cinerus) consists of a single layer of large squamous shaped cells. The RPE cells are but minimally infolded basally (sclerally) but show many large apical (vitreal) processes interdigitating with the rod outer segments. These epithelial cells are joined laterally by prominent tight junctions located in the mid region of the cells. Internally smooth endoplasmic reticulum is very plentiful while rough endoplasmic reticulum is not. Polysomes, small dense mitochondria and small round to oval melanosomes are plentiful. Golgi zones and lysosome-like bodies are also present as are phagosomes of outer segment material and myeloid bodies. The RPE cell nucleus is large and vesicular. It is felt that the melanosomes undergo retinomotor movements but as only light-adapted specimens were examined it is not known how extensive are these movements. Bruch's membrane or complexus basalis shows the typical pentalaminate structure noted for most vertebrates. The choriocapillaris is a single layer of large anastomosing capillaries which are minimally fenestrated facing Bruch's membrane.

  14. Tight Junctions in Salivary Epithelium

    Directory of Open Access Journals (Sweden)

    Olga J. Baker

    2010-01-01

    Full Text Available Epithelial cell tight junctions (TJs consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium.

  15. Deciphering Squamous Cell Carcinoma Using Multidimensional Genomic Approaches

    Directory of Open Access Journals (Sweden)

    Ewan A. Gibb

    2011-01-01

    Full Text Available Squamous cell carcinomas (SqCCs arise in a wide range of tissues including skin, lung, and oral mucosa. Although all SqCCs are epithelial in origin and share common nomenclature, these cancers differ greatly with respect to incidence, prognosis, and treatment. Current knowledge of genetic similarities and differences between SqCCs is insufficient to describe the biology of these cancers, which arise from diverse tissue origins. In this paper we provide a general overview of whole genome approaches for gene and pathway discovery and highlight the advancement of integrative genomics as a state-of-the-art technology in the study of SqCC genetics.

  16. Segmentation and Quantitative Analysis of Epithelial Tissues.

    Science.gov (United States)

    Aigouy, Benoit; Umetsu, Daiki; Eaton, Suzanne

    2016-01-01

    Epithelia are tissues that regulate exchanges with the environment. They are very dynamic and can acquire virtually any shape; at the cellular level, they are composed of cells tightly connected by junctions. Most often epithelia are amenable to live imaging; however, the large number of cells composing an epithelium and the absence of informatics tools dedicated to epithelial analysis largely prevented tissue scale studies. Here we present Tissue Analyzer, a free tool that can be used to segment and analyze epithelial cells and monitor tissue dynamics.

  17. Incidentally Discovered Extensive Squamous Metaplasia within Borderline Phyllodes Tumor: Presentation of a Rare Tumor.

    Science.gov (United States)

    Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar

    2016-01-01

    Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.

  18. Squamous Cell Carcinoma of the Oropharynx and Esophagus with Pulmonary Metastasis in a Backyard Laying Hen.

    Science.gov (United States)

    Laura, Nordio; Marta, Vascellari; Giacomo, Berto; Luca, Bano

    2016-09-01

    A backyard laying hen exhibiting muscular atrophy, dyspnea, and absence of egg production was analyzed for diagnostic insights. Gross findings revealed the presence of a large ulcerated mass with irregular edges involving the caudal part of the oropharynx and the cranial part of the esophagus, occluding the lumen of the esophagus and compressing the trachea. Small nodular lesions were detected also in the lungs. Histologically, both esophageal and pulmonary masses were characterized by nests of pleomorphic epithelial cells with squamous differentiation. The diagnosis was of squamous cell carcinoma of the esophagus with the uncommon feature of pulmonary metastasis.

  19. Squamous papilloma: A report of two cases with review of literature

    Directory of Open Access Journals (Sweden)

    Abhishek Kumar Singh

    2016-01-01

    Full Text Available Squamous papillomas are common lesions of the oral mucosa with predilection for mucosa of hard and soft palate. As an oral lesion, it raises concern because of its clinical appearance, which may mimic an epithelial malignancy such as verrucous carcinoma or condyloma acuminatum. Pathogenesis of this lesion though largely unknown can be attributed to human papillomavirus infection, however, slight controversy regarding its viral origin exists. In this compilation, two cases of oral squamous papilloma are presented along with a review of literature.

  20. Virus interaction with the apical junctional complex.

    Science.gov (United States)

    Gonzalez-Mariscal, Lorenza; Garay, Erika; Lechuga, Susana

    2009-01-01

    In order to infect pathogens must breach the epithelial barriers that separate the organism from the external environment or that cover the internal cavities and ducts of the body. Epithelia seal the passage through the paracellular pathway with the apical junctional complex integrated by tight and adherens junctions. In this review we describe how viruses like coxsackie, swine vesicular disease virus, adenovirus, reovirus, feline calcivirus, herpes viruses 1 and 2, pseudorabies, bovine herpes virus 1, poliovirus and hepatitis C use as cellular receptors integral proteins present at the AJC of epithelial cells. Interaction with these proteins contributes in a significant manner in defining the particular tropism of each virus. Besides these proteins, viruses exhibit a wide range of cellular co-receptors among which proteins present in the basolateral cell surface like integrins are often found. Therefore targeting proteins of the AJC constitutes a strategy that might allow viruses to bypass the physical barrier that blocks their access to receptors expressed on the basolateral surface of epithelial cells.

  1. Differential Effects of TNF (TNFSF2) and IFN-gamma on Intestinal Epithelial Cell Morphogenesis and Barrier Function in Three-Dimensional Culture

    NARCIS (Netherlands)

    Juuti-Uusitalo, Kati; Klunder, Leon J.; Sjollema, Klaas A.; Mackovicova, Katarina; Ohgaki, Ryuichi; Hoekstra, Dick; Dekker, Jan; van Ijzendoorn, Sven C. D.

    2011-01-01

    Background: The cytokines TNF (TNFSF2) and IFN gamma are important mediators of inflammatory bowel diseases and contribute to enhanced intestinal epithelial permeability by stimulating apoptosis and/or disrupting tight junctions. Apoptosis and tight junctions are also important for epithelial tissue

  2. Mechanics of epithelial tissue homeostasis and morphogenesis.

    Science.gov (United States)

    Guillot, Charlène; Lecuit, Thomas

    2013-06-07

    Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.

  3. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

  4. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R.; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A.; Bielenberg, Diane R.

    2017-01-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID:26877262

  5. Transgenic overexpression of cdx1b induces metaplastic changes of gene expression in zebrafish esophageal squamous epithelium.

    Science.gov (United States)

    Hu, Bo; Chen, Hao; Liu, Xiuping; Zhang, Chengjin; Cole, Gregory J; Lee, Ju-Ahng; Chen, Xiaoxin

    2013-06-01

    Cdx2 has been suggested to play an important role in Barrett's esophagus or intestinal metaplasia (IM) in the esophagus. To investigate whether transgenic overexpression of cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of zebrafish esophageal squamous epithelium, a transgenic zebrafish system was developed by expressing cdx1b gene under the control of zebrafish keratin 5 promoter (krt5p). Gene expression in the esophageal squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation, and apoptosis were analyzed by hematoxylin & eosin (HE) staining, Periodic acid Schiff (PAS) Alcian blue staining, proliferating cell nuclear antigen (PCNA) immunohistochemical staining, and TUNEL assay as well. cdx1b was found to be overexpressed in the nuclei of esophageal squamous epithelial cells of the transgenic zebrafish. Ectopic expression of cdx1b disturbed the development of this epithelium in larval zebrafish and induced metaplastic changes in gene expression in the esophageal squamous epithelial cells of adult zebrafish, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, cdx1b failed to induce histological IM, or to modulate cell proliferation and apoptosis in the squamous epithelium of adult transgenic zebrafish.

  6. An Important Member of Tight Junctions: Claudins

    Directory of Open Access Journals (Sweden)

    Ozlem Demirpence

    2016-01-01

    Full Text Available The tight junction (TJs, the most apically located of the intercellular junctional complexes, inhibits solute and water flow through the paracellular space, termed the %u201Cbarrier%u201D function. TJs participate in signal transduction mechanisms that regulate epithelial cell proliferation, gene expression, differentiation and morphogenesis. The claudin family of transmembrane proteins localized to the TJ. Loss of expression of Claudin causes of suppression TJs function. Recent studies have shown that altered levels of the different claudins may be related to invasion and progression of carcinoma cells in several primary neoplasms. A better knowledge of the mechanisms underlying carcinogenesis will likely result in the development of novel approaches for the diagnosis and therapy.

  7. Magnetic tunnel junctions (MTJs)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We review the giant tunnel magnetoresistance (TMR) in ferromagnetic-insulator-ferromagnetic junctions discovered in recent years, which is the magnetoresistance (MR) associated with the spin-dependent tunneling between two ferromagnetic metal films separated by an insulating thin tunnel barrier. The theoretical and experimental results including junction conductance, magnetoresistance and their temperature and bias dependences are described.

  8. Stacked Josephson Junctions

    DEFF Research Database (Denmark)

    Madsen, Søren Find; Pedersen, Niels Falsig; Christiansen, Peter Leth

    2010-01-01

    Long Josephson junctions have for some time been considered as a source of THz radiation. Solitons moving coherently in the junctions is a possible source for this radiation. Analytical computations of the bunched state and bunching-inducing methods are reviewed. Experiments showing THz radiation...

  9. Balancing spatially regulated β-actin translation and dynamin-mediated endocytosis is required to assemble functional epithelial monolayers.

    Science.gov (United States)

    Cruz, Lissette A; Vedula, Pavan; Gutierrez, Natasha; Shah, Neel; Rodriguez, Steven; Ayee, Brian; Davis, Justin; Rodriguez, Alexis J

    2015-12-01

    Regulating adherens junction complex assembly/disassembly is critical to maintaining epithelial homeostasis in healthy epithelial tissues. Consequently, adherens junction structure and function is often perturbed in clinically advanced tumors of epithelial origin. Some of the most studied factors driving adherens junction complex perturbation in epithelial cancers are transcriptional and epigenetic down-regulation of E-cadherin expression. However, numerous reports demonstrate that post-translational regulatory mechanisms such as endocytosis also regulate early phases of epithelial-mesenchymal transition and metastatic progression. In already assembled healthy epithelia, E-cadherin endocytosis recycles cadherin-catenin complexes to regulate the number of mature adherens junctions found at cell-cell contact sites. However, following de novo epithelial cell-cell contact, endocytosis negatively regulates adherens junction assembly by removing E-cadherin from the cell surface. By contrast, following de novo epithelial cell-cell contact, spatially localized β-actin translation drives cytoskeletal remodeling and consequently E-cadherin clustering at cell-cell contact sites and therefore positively regulates adherens junction assembly. In this report we demonstrate that dynamin-mediated endocytosis and β-actin translation-dependent cadherin-catenin complex anchoring oppose each other following epithelial cell-cell contact. Consequently, the final extent of adherens junction assembly depends on which of these processes is dominant following epithelial cell-cell contact. We expressed β-actin transcripts impaired in their ability to properly localize monomer synthesis (Δ3'UTR) in MDCK cells to perturb actin filament remodeling and anchoring, and demonstrate the resulting defect in adherens junction structure and function is rescued by inhibiting dynamin mediated endocytosis. Therefore, we demonstrate balancing spatially regulated β-actin translation and dynamin

  10. Epithelial abnormalities and precancerous lesions of anterior urethra in patients with penile carcinoma: a report of 89 cases.

    Science.gov (United States)

    Velazquez, Elsa F; Soskin, Ana; Bock, Adelaida; Codas, Ricardo; Cai, Guoping; Barreto, Jose E; Cubilla, Antonio L

    2005-07-01

    Urethral and penile tissues and their neoplasms are considered anatomically and pathogenetically different. Since we observed urethral dysplastic lesions and some similarities between noninvasive and invasive lesions of the anterior urethra and glans, we designed this study to document epithelial urethral abnormalities in patients with penile squamous cell carcinoma. We examined urethral epithelia from 170 penectomies with invasive squamous cell carcinoma finding a variety of primary epithelial abnormalities in 89 cases (52%) and secondary invasion of penile carcinoma to urethra in 42 cases (25%). Patients' average age was 68 years. Primary tumors measured 4 cm in average diameter and the majority were squamous cell carcinoma of the usual (67%) or verrucous type (15%). Primary epithelial abnormalities found were squamous intraepithelial lesions, metaplasias and microglandular hyperplasias. Urethral squamous intraepithelial lesions of high grade was found in six patients and of low grade in eight cases. Squamous metaplasia, seen in 69 cases, was the most frequent finding. Metaplasias were classified as nonkeratinizing and keratinizing. Nonkeratinizing metaplasias (57 cases) were variegated in morphology: simplex (26 cases), hyperplastic (12 cases), clear cell (11 cases) and spindle (8 cases). Keratinizing metaplasias (12 cases) showed hyperkeratosis and were more frequently associated with verrucous than nonverrucous penile squamous cell carcinoma. Microglandular hyperplasia was present in eight cases. Lichen sclerosus was associated with simplex squamous metaplasia in four cases. Despite the large size of the primary tumors, direct urethral invasion by penile carcinoma was present in only 25% of the cases. The presence of precancerous lesions in urethra of patients with penile carcinoma indicates urethral participation in the pathogenesis of penile cancer. Simplex squamous metaplasia is a common finding probably related to chronic inflammation. Keratinizing and

  11. Current smoking-specific gene expression signature in normal bronchial epithelium is enhanced in squamous cell lung cancer

    NARCIS (Netherlands)

    Boelens, Mirjam C.; van den Berg, Anke; Fehrmann, Rudolf S. N.; Geerlings, Marie; de Jong, Wouter K.; te Meerman, Gerard J; Sietsma, Hannie; Timens, Winn; Postma, Dirkje S.; Groen, Harry J. M.

    2009-01-01

    Cigarette smoking is the main risk factor for the development of squamous cell lung carcinoma (SCC). However, the smoking-related molecular changes in SCC have not been studied. Gene expression studies in both histologically normal bronchial epithelium and SCC epithelial samples identified genes dif

  12. Sonic hedgehog in oral squamous cell carcinoma: An immunohistochemical study

    Science.gov (United States)

    Srinath, Sahana; Iyengar, Asha R; Mysorekar, Vijaya

    2016-01-01

    Background: Recent studies have revealed the involvement of hedgehog (Hh) signaling component in proliferation and invasive behavior of many carcinomas. Aim: This study aims to identify the expression of sonic Hh (SHH) protein of SHH pathway in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) using SHH (H-160) (Santa Cruz, sc-9042) which could have therapeutic implication in future. Materials and Methods: A total of 250 cases comprising 50 normal oral mucosa, 50 cases of oral epithelial dysplasia, 50 well, 50 moderate and 50 poorly differentiated OSCCs were included in the study. Immunohistochemical evaluation of SHH protein expression was conducted using monoclonal antibody. Interpretation of the expression was done by immunoreactive score of Remmele and Stegner (IRS) scoring method. Statistical Analysis: Chi-Square test was used to analyze the results. Results: The study showed that SHH signaling molecules are highly expressed in OSCC, and their expression was mainly in the cytoplasm of epithelial cells. Conclusion: The SHH signaling component is associated with the pathological parameter in OSCC and oral epithelial dysplasia. PMID:27721600

  13. Pseudoangiomatous squamous cell carcinoma in the oral cavity of a dog.

    Science.gov (United States)

    Cushing, Tim; Barnard, Sandra; Fleis, Rebekah; Peters, Rachel

    2010-03-01

    An 8-year-old, spayed, female Labrador Retriever mixed-breed dog was presented to the Cornell University Hospital for Animals with an invasive oral mass involving the upper left fourth premolar and first molar teeth. Initial biopsy results suggested a poorly differentiated squamous cell carcinoma, whereas further histologic examination of the surgically removed mass revealed a hemangiosarcoma-like mass composed of numerous vascular clefts and variable numbers of keratinizing epithelial cells. Histologic and immunohistochemical characteristics were compatible with pseudoangiomatous squamous cell carcinoma, a well-recognized human variant of acanthomatous squamous cell carcinoma. Because of histomorphologic similarities with canine gingival hemangiosarcoma, diagnosticians should be aware of the present tumor variant as a differential diagnosis for vascular-like growths in the oral cavity of dogs.

  14. A Case of Squamous Cell Carcinoma in the External Auditory Canal Previously Treated for Verrucous Carcinoma.

    Science.gov (United States)

    Nam, Soo Jung; Yang, Chan Joo; Chung, Jong Woo

    2016-12-01

    Carcinoma in the external auditory canal (EAC) is a rare malignancy with an annual incidence of one per one million people, accounting for less than 0.2% of all head and neck cancers. The most common histopathological type of EAC cancer is squamous cell carcinoma. Verrucous carcinoma is a well-differentiated, low-grade variant of squamous cell carcinoma. It is a locally destructive, invasive, and slow growing tumor that rarely metastasizes. Verrucous carcinoma occurs predominantly in the oral cavity and larynx, and its occurrence in the EAC is extremely rare. In this report, we present a histologically confirmed case of verrucous carcinoma in the EAC and temporal bone, which for several years had been classified as epithelial hyperplasia. Two-and-a-half years after diagnosis of verrucous carcinoma, a recurrent mass was found and the lesion was then confirmed to be squamous cell carcinoma.

  15. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  16. Studying cytokinesis in Drosophila epithelial tissues.

    Science.gov (United States)

    Pinheiro, D; Bellaïche, Y

    2017-01-01

    Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis.

  17. Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

    Science.gov (United States)

    Rodríguez, F; Castro, P; Ramírez, G A

    2016-05-01

    A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog.

  18. NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry.

    Science.gov (United States)

    Ebrahim, Seham; Fujita, Tomoki; Millis, Bryan A; Kozin, Elliott; Ma, Xuefei; Kawamoto, Sachiyo; Baird, Michelle A; Davidson, Michael; Yonemura, Shigenobu; Hisa, Yasuo; Conti, Mary Anne; Adelstein, Robert S; Sakaguchi, Hirofumi; Kachar, Bechara

    2013-04-22

    Nonmuscle myosin II (NMII) is thought to be the master integrator of force within epithelial apical junctions, mediating epithelial tissue morphogenesis and tensional homeostasis. Mutations in NMII are associated with a number of diseases due to failures in cell-cell adhesion. However, the organization and the precise mechanism by which NMII generates and responds to tension along the intercellular junctional line are still not known. We discovered that periodic assemblies of bipolar NMII filaments interlace with perijunctional actin and α-actinin to form a continuous belt of muscle-like sarcomeric units (∼400-600 nm) around each epithelial cell. Remarkably, the sarcomeres of adjacent cells are precisely paired across the junctional line, forming an integrated, transcellular contractile network. The contraction/relaxation of paired sarcomeres concomitantly impacts changes in apical cell shape and tissue geometry. We show differential distribution of NMII isoforms across heterotypic junctions and evidence for compensation between isoforms. Our results provide a model for how NMII force generation is effected along the junctional perimeter of each cell and communicated across neighboring cells in the epithelial organization. The sarcomeric network also provides a well-defined target to investigate the multiple roles of NMII in junctional homeostasis as well as in development and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Magnifying endoscopy with narrow-band imaging findings in the diagnosis of Barrett's esophageal adenocarcinoma spreading below squamous epithelium.

    Science.gov (United States)

    Omae, Masami; Fujisaki, Junko; Shimizu, Tomoki; Igarashi, Masahiro; Yamamoto, Noriko

    2013-05-01

    It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.

  20. Primary orbital squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ana L. Campos Arbulú

    2017-02-01

    Full Text Available Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis

  1. Equivalent Josephson junctions

    Science.gov (United States)

    Boyadjiev, T. L.; Semerdjieva, E. G.; Shukrinov, Yu. M.

    2008-01-01

    The magnetic field dependences of critical current are numerically constructed for a long Josephson junction with a shunt-or resistor-type microscopic inhomogeneities and compared to the critical curve of a junction with exponentially varying width. The numerical results show that it is adequate to replace the distributed inhomogeneity of a long Josephson junction by an inhomogeneity localized at one of its ends, which has certain technological advantages. It is also shown that the critical curves of junctions with exponentially varying width and inhomogeneities localized at the ends are unaffected by the mixed fluxon-antifluxon distributions of the magnetic flow. This fact may explain the improvement of the spectra of microwave radiation noted in the literature.

  2. Membrane dynamics and the regulation of epithelial cell polarity

    NARCIS (Netherlands)

    van der Wouden, JM; Maier, O; van IJzendoorn, SCD; Hoekstra, D

    2003-01-01

    Plasma membranes of epithelial cells consist of two domains, an apical and a basolateral domain, the surfaces of which differ in composition. The separation of these domains by a tight junction and the fact that specific transport pathways exist for intracellular communication between these domains

  3. Crossroads of Wnt and Hippo in epithelial tissues.

    Science.gov (United States)

    Bernascone, Ilenia; Martin-Belmonte, Fernando

    2013-08-01

    Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues.

  4. Quantum Junction Solar Cells

    KAUST Repository

    Tang, Jiang

    2012-09-12

    Colloidal quantum dot solids combine convenient solution-processing with quantum size effect tuning, offering avenues to high-efficiency multijunction cells based on a single materials synthesis and processing platform. The highest-performing colloidal quantum dot rectifying devices reported to date have relied on a junction between a quantum-tuned absorber and a bulk material (e.g., TiO 2); however, quantum tuning of the absorber then requires complete redesign of the bulk acceptor, compromising the benefits of facile quantum tuning. Here we report rectifying junctions constructed entirely using inherently band-aligned quantum-tuned materials. Realizing these quantum junction diodes relied upon the creation of an n-type quantum dot solid having a clean bandgap. We combine stable, chemically compatible, high-performance n-type and p-type materials to create the first quantum junction solar cells. We present a family of photovoltaic devices having widely tuned bandgaps of 0.6-1.6 eV that excel where conventional quantum-to-bulk devices fail to perform. Devices having optimal single-junction bandgaps exhibit certified AM1.5 solar power conversion efficiencies of 5.4%. Control over doping in quantum solids, and the successful integration of these materials to form stable quantum junctions, offers a powerful new degree of freedom to colloidal quantum dot optoelectronics. © 2012 American Chemical Society.

  5. The expression andprognostic value ofprotein tyrosine kinase 6 inearly-stage cervical squamous cell cancer

    Institute of Scientific and Technical Information of China (English)

    XiaoJingWang; YingXiong; ZeBiaoMa; JianChuanXia; YanFangLi

    2016-01-01

    Background:Protein tyrosine kinase 6 (PTK6) is overexpressed in many epithelial tumors and predicts poor progno‑sis. However, PTK6 expression status and its role in cervical squamous cell cancer are unknown. This study aimed to investigate the expression level and clinical signiifcance of PTK6 in early‑stage cervical squamous cell cancer. Methods:Quantitative reverse transcription‑polymerase chain reaction (qRT‑PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen, early‑stage cervical squamous cell cancer specimens and adjacent non‑tumorous cervical tissues. The expression of PTK6 was detected using immuno‑histochemical staining in 150 formalin‑ifxed, paraffn‑embedded, early‑stage cervical squamous cell cancer sections and 10 normal cervical tissue sections. Results:The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non‑tumorous cervical tissues. Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells. The level of PTK6 expression was signiif‑cantly associated with tumor grade (P=0.020). The 5‑year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression (81.3% vs. 96.2%,P=0.008). Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival (hazard ratio=5.999, 95% conifdence interval 1.622–22.191,P Conclusions:PTK6 is overexpressed in cervical squamous cell cancer. Increased PTK6 expression is associated with reduced 5‑year overall survival. PTK6 expression is an independent prognostic predictor for cervical cancer.

  6. Trefoil factor 3 as a novel biomarker to distinguish between adenocarcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Wang, Xiao-Nan; Wang, Shu-Jing; Pandey, Vijay; Chen, Ping; Li, Qing; Wu, Zheng-Sheng; Wu, Qiang; Lobie, Peter E

    2015-05-01

    In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an additional

  7. Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila.

    Science.gov (United States)

    Chihara, Takahiro; Kato, Kagayaki; Taniguchi, Misako; Ng, Julian; Hayashi, Shigeo

    2003-04-01

    Cell rearrangement, accompanied by the rapid assembly and disassembly of cadherin-mediated cell adhesions, plays essential roles in epithelial morphogenesis. Various in vitro and cell culture studies on the small GTPase Rac have suggested it to be a key regulator of cell adhesion, but this notion needs to be verified in the context of embryonic development. We used the tracheal system of Drosophila to investigate the function of Rac in the epithelial cell rearrangement, with a special attention to its role in regulating epithelial cadherin activity. We found that a reduced Rac activity led to an expansion of cell junctions in the embryonic epidermis and tracheal epithelia, which was accompanied by an increase in the amount of Drosophila E-Cadherin-Catenin complexes by a post-transcriptional mechanism. Reduced Rac activity inhibited dynamic epithelial cell rearrangement. Hyperactivation of Rac, on the other hand, inhibited assembly of newly synthesized E-Cadherin into cell junctions and caused loss of tracheal cell adhesion, resulting in cell detachment from the epithelia. Thus, in the context of Drosophila tracheal development, Rac activity must be maintained at a level necessary to balance the assembly and disassembly of E-Cadherin at cell junctions. Together with its role in cell motility, Rac regulates plasticity of cell adhesion and thus ensures smooth remodeling of epithelial sheets into tubules.

  8. Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

    Science.gov (United States)

    2016-09-20

    Colorectal Cancer; Gastric Adenocarcinoma; Esophageal Cancer; Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Ovarian Epithelial Cancer; Carcinoma Breast Stage IV; Hormone-refractory Prostate Cancer; Pancreatic Ductal Adenocarcinoma; Head and Neck Cancers- Squamous Cell; Renal Cell Cancer; Urinary Bladder Neoplasms; Cervical Cancer; Endometrial Cancer; Follicular Thyroid Cancer; Glioblastoma Multiforme

  9. Endoscopic laser treatment in pre-malignant and malignant vocal fold epithelial lesions.

    NARCIS (Netherlands)

    Remijn, E.E.; Marres, H.A.M.; Hoogen, F.J.A. van den

    2002-01-01

    Endoscopic laser treatment was performed in 43 patients with pre-malignant or malignant vocal fold epithelial lesions, 10 were treated with endoscopic laser surgery for dysplasia, 12 for carcinoma in situ (CIS), five for verrucous carcinoma and 16 patients for squamous cell carcinoma (SCC). Thirty-t

  10. Gene expression profile comparison of Barrett's esophagus epithelial cell cultures and biopsies

    NARCIS (Netherlands)

    van Baal, J. W. P. M.; Rygiel, A. M.; Milano, F.; Anderson, M.; Bergman, J. J. G. H. M.; Spek, C. A.; Wang, K. K.; Peppelenbosch, M. P.; Krishnadath, K. K.

    2008-01-01

    Barrett's esophagus (BE) is a metaplastic process in which the normal squamous epithelium of the distal esophagus is replaced by columnar lined epithelium. The aim was to gain more insight in the process of metaplasia and to identify which genes are specifically expressed by the epithelial cells and

  11. Endoscopic laser treatment in pre-malignant and malignant vocal fold epithelial lesions.

    NARCIS (Netherlands)

    Remijn, E.E.; Marres, H.A.M.; Hoogen, F.J.A. van den

    2002-01-01

    Endoscopic laser treatment was performed in 43 patients with pre-malignant or malignant vocal fold epithelial lesions, 10 were treated with endoscopic laser surgery for dysplasia, 12 for carcinoma in situ (CIS), five for verrucous carcinoma and 16 patients for squamous cell carcinoma (SCC).

  12. Breast Metastasis from Esophagogastric Junction Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Sanghamitra Jena

    2014-01-01

    Full Text Available Metastasis to breast from nonmammary malignancy is only about 1.3–2.7%. A few cases of squamous cell carcinoma of esophagus and adenocarcinoma of stomach metastasizing to breast have been reported, but this is probably the first report of breast metastasis from esophagogastric junction (EGJ cancer in the English literature. Herein we report a case of a 32-year-old patient diagnosed as adenocarcinoma of gastroesophageal junction, presenting with left breast metastasis two years after treatment. Given unusual site of metastasis in a follow-up case of EGJ cancer, not only it is challenging to differentiate it from primary carcinoma of breast but also it is important from treatment point of view. In our case, clinical data, radiology, histopathology, and immunohistochemistry (IHC led us to reach the diagnosis.

  13. Mechanism of cytokine modulation of epithelial tight junction barrier

    OpenAIRE

    Al-Sadi, Rana; Boivin, Michel; Ma, Thomas

    2009-01-01

    Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-α, interferon-γ, interleukin-1β (IL-1β), and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-β are important in the attenuation or containment of inflammatory process. It is increasingly recognized that cytokines have an im...

  14. Distribution of the feline calicivirus receptor junctional adhesion molecule a in feline tissues.

    Science.gov (United States)

    Pesavento, P A; Stokol, T; Liu, H; van der List, D A; Gaffney, P M; Parker, J S

    2011-03-01

    Junctional adhesion molecule A (JAM-A) is an immunoglobulin superfamily protein that plays an important role in the assembly and maintenance of tight junctions and the establishment of epithelial cell polarity. The feline JAM-A (fJAM-A) is a functional receptor for feline calicivirus (FCV). Among natural diseases associated with FCV infection, isolates that cause oral vesicular disease are detected in epithelial cells; however, isolates that cause systemic disease are detected in multiple cell types. The distribution of an FCV receptor or receptors in feline tissues is relevant to viral pathogenesis in that it should reflect the wide latitude of clinical sequelae associated with FCV infection. The authors examined the expression of feline JAM-A in the cat by using confocal immunofluorescence localization on normal tissues, with special regard to tissue targets of naturally occurring FCV. As described in the human and the mouse, fJAM-A was widely distributed in feline tissues, where it localized at cell-cell junctions of epithelial and endothelial cells. fJAM-A was highly expressed on feline platelets, with lower levels of expression on feline peripheral blood leukocytes. Additionally, FCV infection of a feline epithelial cell monolayer causes redistribution of fJAM-A to the cytosol of infected cells. It is reasonable to propose that the spectrum of lesions caused by FCV reflects disruption of intercellular junctions that rely on fJAM-A function and tight junctional integrity.

  15. Gap junction modulation by extracellular signaling molecules: the thymus model

    Directory of Open Access Journals (Sweden)

    Alves L.A.

    2000-01-01

    Full Text Available Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

  16. Two new septate junctions in the phylum Coelenterata.

    Science.gov (United States)

    Green, C R; Flower, N E

    1980-04-01

    Freeze-fracture of fixed and unfixed tissue, lanthanum tracer and conventional thin-section studies have revealed 2 new types of septate junction in the class Anthozoa, phylum Coelenterata. These new junctions have the 15-18-nm intercellular spacing of all other described septate junctions and are found around the apical circumference of cells lining a lumen or outside edge. However, in freeze-fracture replicas and tangential views of lanthanum-impregnated tissue, they are seen to be quite different from other known septate junction types. One of the new junctions is found in endothelial tissue such as that lining the gut or the inside of the tentacles. In tangential view it is seen to consist of relatively short, straight, double septa, again with lateral projections. In feeeze-fracture of unfixed tissue, the junction consists of double rows of particles on the P face, the particles of one row being rounded, those of the other being elongated at right angles to the line of the septum. This dichotomy in particle size is unexpected, as the 2 halves of the septa as seen in tangential view are symmetrical. In freeze-fracture of fixed material the particle arrays remain on the P face and appear similar to those of unfixed material, but never as clear. In fixed tissue, some distortion had occurred and in extreme cases septa appear as a single broad jumbled row of particles. In this double septa junction, the rows of particles seen in freeze-fracture are occasionally seen to anastomose with a septum dividing into 2 and a third row of particles aligning with the 2 new septa to form their double particle rows. In both fixed and unfixed tissues, the E face of the junction consists of wide, shallow grooves. The second of the new junctions occurs in epithelial tissue, such as around the outer edge of sea-anemone tentacles, and consists of long wavy septa with lateral projections. In views where these projections appear longest, they arise predominantly from one side of the

  17. Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

    Science.gov (United States)

    Rice, Thomas W; Gress, Donna M; Patil, Deepa T; Hofstetter, Wayne L; Kelsen, David P; Blackstone, Eugene H

    2017-07-08

    Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society. © 2017 American Cancer Society.

  18. Epithelial-mesenchymal transition: Understanding the basic concept

    Directory of Open Access Journals (Sweden)

    Suresh Babu Ghanta

    2012-01-01

    Full Text Available The epithelial-mesenchymal transition (EMT is described as a rapid and reversible process of change of cell phenotype seen during embryonic development, organ fibrosis, and tumor progression. EMT was first described by Gary Greenberg and Elizabeth Hay in 1982. During EMT the epithelial cells alter their cell polarity, reorganize their cytoskeleton thus become isolated and motile. Depending upon the biological context in which they occur, EMT is divided into three types namely EMT type I, II, III. The article describes the process of EMT implicated in the oral cavity as in palate and root development (type I EMT, gingival fibromatosis and oral sub-mucous fibrosis (type II EMT, and oral squamous cell carcinoma (type III EMT. The reverse process of EMT is called as mesenchymal-epithelial transition seen in association with kidney formation.

  19. The Preliminary Experimental Study of Induced Differentiation of Embryonic Stem Cells into Corneal Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Ling Yu; Jian Ge; Zhichong Wang; Bing Huang; Keming Yu; Chongde Long; Xigu Chen

    2001-01-01

    Purpose:To study preliminarily induced differentiation of embryonic stem cells intocorneal epithelial cells in vitro.Methods: Murine embryonic stem cells were co-cultured with Rabbit limbal cornealepithelial cells in Transwell system to induce differentiation. Mophological andimmunohistochemical examination were implemented.Results: The induced cells from embryonic stem cells have an epithelial appearance.The cells formed a network and were confluent into film gradually after beingco-cultured with rabbit limbal corneal epithelial cells for 24 ~ 96 hours. The cells rangedmosaic structure and localized together with clear rim. Most of the cells showedpolygonal appearance. Transmission electron microscope showed lots of microvilli on thesurface of induced cells and tight junctions between them. These epithelial-like cellsexpressed the corneal epithelial cell specific marker cytokeratin3/cytokeratinl2.Conclusion: The potential mechanism of the differentiation of murine embryonic stemcells into corneal epithelial cells induced by limbal corneal epithelial cell-derivedinducing activity is to be further verified.

  20. Management of Anal Squamous Intraepithelial Lesions

    OpenAIRE

    Pineda, Carlos E.; Welton, Mark L.

    2009-01-01

    Anal squamous intraepithelial lesions include both low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and are caused by chronic infection with the human papillomavirus (HPV). The disease is increasing in both incidence and prevalence, especially among patients with the following risk factors: homosexual men, acquired or iatrogenic immunosuppression, and presence of other HPV-related diseases. Although the natural history of the disease is ...

  1. Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

    Directory of Open Access Journals (Sweden)

    Balda Maria S

    2009-12-01

    Full Text Available Abstract Background Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Results Here we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance. Conclusions Our data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties.

  2. The human myotendinous junction

    DEFF Research Database (Denmark)

    Knudsen, A B; Larsen, M; Mackey, Abigail

    2015-01-01

    The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never ...

  3. Doped semiconductor nanocrystal junctions

    Energy Technology Data Exchange (ETDEWEB)

    Borowik, Ł.; Mélin, T., E-mail: thierry.melin@isen.iemn.univ-lille1.fr [Institut d’Electronique, de Microélectronique et de Nanotechnologie, CNRS-UMR8520, Avenue Poincaré, F-59652 Villeneuve d’Ascq (France); Nguyen-Tran, T.; Roca i Cabarrocas, P. [Laboratoire de Physique des Interfaces et des Couches Minces, CNRS-UMR7647, Ecole Polytechnique, F-91128 Palaiseau (France)

    2013-11-28

    Semiconductor junctions are the basis of electronic and photovoltaic devices. Here, we investigate junctions formed from highly doped (N{sub D}≈10{sup 20}−10{sup 21}cm{sup −3}) silicon nanocrystals (NCs) in the 2–50 nm size range, using Kelvin probe force microscopy experiments with single charge sensitivity. We show that the charge transfer from doped NCs towards a two-dimensional layer experimentally follows a simple phenomenological law, corresponding to formation of an interface dipole linearly increasing with the NC diameter. This feature leads to analytically predictable junction properties down to quantum size regimes: NC depletion width independent of the NC size and varying as N{sub D}{sup −1/3}, and depleted charge linearly increasing with the NC diameter and varying as N{sub D}{sup 1/3}. We thus establish a “nanocrystal counterpart” of conventional semiconductor planar junctions, here however valid in regimes of strong electrostatic and quantum confinements.

  4. A reverse Warburg metabolism in oral squamous cell carcinoma is not dependent upon myofibroblasts

    DEFF Research Database (Denmark)

    Jensen, David Hebbelstrup; Therkildsen, Marianne Hamilton; Dabelsteen, Erik

    2015-01-01

    The reverse Warburg effect describes the phenomenon that epithelial cancer cells take advantage of the metabolic machinery from nearby cancer-associated fibroblast, inducing them to produce lactate and ketones to fuel the high metabolic demands of the epithelial tumour tissues. This is in breast...... cancer observed as a lack of stromal caveolin-1 (CAV-1) and an increased expression of monocarboxylate transporter 4 (MCT-4) in the tumour stroma, with a concomitant increase in the expression of monocarboxylate transporter 1 (MCT-1) in the epithelial, tumour compartment. The lack of CAV-1 and increased...... expression of MCT-4 have been shown to have prognostic importance, primarily in patients with breast cancer. However, this phenomenon has only scarcely been described in oral squamous cell carcinoma (OSCC). Given the prognostic importance of myofibroblasts in OSCC, we also examined a potential relationship...

  5. Photofrin-mediated photodynamic therapy of chemically-induced premalignant lesions and squamous cell carcinoma of the palatal mucosa in rats

    NARCIS (Netherlands)

    Nauta, JM; vanLeengoed, HLLM; Witjes, MJH; Nikkels, PGJ; Vermey, A; Roodenburg, JLN

    1997-01-01

    Photodynamic therapy (PDT), an experimental cancer therapy, was studied in an animal model of chemically-induced epithelial dysplasia and squamous cell carcinoma. PDT was performed 24 hours after i.v. injection of 2.5 mg/kg bw Photofrin, and using 100 J/cm(2) incident light at two activation wavelen

  6. Junction trees of general graphs

    Institute of Scientific and Technical Information of China (English)

    Xiaofei WANG; Jianhua GUO

    2008-01-01

    In this paper,we study the maximal prime subgraphs and their corresponding structure for any undirected graph.We introduce the notion of junction trees and investigate their structural characteristics,including junction properties,induced-subtree properties,running-intersection properties and maximum-weight spanning tree properties.Furthermore,the characters of leaves and edges on junction trees are discussed.

  7. Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.

    Science.gov (United States)

    Lechuga, Susana; Ivanov, Andrei I

    2017-03-16

    The intestinal epithelium forms a key protective barrier that separates internal organs from the harmful environment of the gut lumen. Increased permeability of the gut barrier is a common manifestation of different inflammatory disorders contributing to the severity of disease. Barrier permeability is controlled by epithelial adherens junctions and tight junctions. Junctional assembly and integrity depend on fundamental homeostatic processes such as cell differentiation, rearrangements of the cytoskeleton, and vesicle trafficking. Alterations of intestinal epithelial homeostasis during mucosal inflammation may impair structure and remodeling of apical junctions, resulting in increased permeability of the gut barrier. In this review, we summarize recent advances in our understanding of how altered epithelial homeostasis affects the structure and function of adherens junctions and tight junctions in the inflamed gut. Specifically, we focus on the transcription reprogramming of the cell, alterations in the actin cytoskeleton, and junctional endocytosis and exocytosis. We pay special attention to knockout mouse model studies and discuss the relevance of these mechanisms to human gastrointestinal disorders.

  8. Characterization and significance of adhesion and junction-related proteins in mouse ovarian follicles.

    Science.gov (United States)

    Mora, Jocelyn M; Fenwick, Mark A; Castle, Laura; Baithun, Marianne; Ryder, Timothy A; Mobberley, Margaret; Carzaniga, Raffaella; Franks, Stephen; Hardy, Kate

    2012-05-01

    In the ovary, initiation of follicle growth is marked by cuboidalization of flattened granulosa cells (GCs). The regulation and cell biology of this shape change remains poorly understood. We propose that characterization of intercellular junctions and associated proteins is key to identifying as yet unknown regulators of this important transition. As GCs are conventionally described as epithelial cells, this study used mouse ovaries and isolated follicles to investigate epithelial junctional complexes (tight junctions [TJ], adherens junctions [AJ], and desmosomes) and associated molecules, as well as classic epithelial markers, by quantitative PCR and immunofluorescence. These junctions were further characterized using ultrastructural, calcium depletion and biotin tracer studies. Junctions observed by transmission electron microscopy between GCs and between GCs and oocyte were identified as AJs by expression of N-cadherin and nectin 2 and by the lack of TJ and desmosome-associated proteins. Follicles were also permeable to biotin, confirming a lack of functional TJs. Surprisingly, GCs lacked all epithelial markers analyzed, including E-cadherin, cytokeratin 8, and zonula occludens (ZO)-1alpha+. Furthermore, vimentin was expressed by GCs, suggesting a more mesenchymal phenotype. Under calcium-free conditions, small follicles maintained oocyte-GC contact, confirming the importance of calcium-independent nectin at this stage. However, in primary and multilayered follicles, lack of calcium resulted in loss of contact between GCs and oocyte, showing that nectin alone cannot maintain attachment between these two cell types. Lack of classic markers suggests that GCs are not epithelial. Identification of AJs during GC cuboidalization highlights the importance of AJs in regulating initiation of follicle growth.

  9. The function of tight junctions in maintaining differences in lipid composition between the apical and the basolateral cell surface domains of MDCK cells

    NARCIS (Netherlands)

    van Meer, G.|info:eu-repo/dai/nl/068570368; Simons, K.

    1986-01-01

    Tight junctions in epithelial cells have been postulated to act as barriers inhibiting lateral diffusion of lipids and proteins between the apical and basolateral plasma membrane domains. To study the fence function of the tight junction in more detail, we have fused liposomes containing the

  10. Cisplatin, Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2016-05-16

    Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  11. True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma). A case report.

    Science.gov (United States)

    Adachi, H; Morimura, T; Yumoto, T; Ikeda, M; Fukui, H

    1992-10-01

    True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma) originating in the right lower lobe in a 62-year-old Japanese male is reported. The tumor, measuring 5.5 x 3.5 x 3.5 cm, was markedly necrotic and its apex protruded into the bronchial lumen. Light microscopy showed that the tumor was composed of squamous cell carcinoma with sarcomatous spindle or polygonal cell proliferation and true chondrosarcoma. Immunohistochemically, the cytoplasm of numerous cells of the squamous cell carcinoma component was stained with anti-cytokeratin (PKK 1) and the cytoplasmic membrane with anti-epithelial membrane antigen (EMA). Although sarcomatous regions were stained with anti-vimentin (vimentin) and no tumor cells were reactive for EMA, a few tumor cells were positive for PKK 1. The cytoplasm of numerous chondrosarcoma cells was positively stained for vimentin and S-100 protein. Based on these findings, we concluded that the present tumor was a true carcinosarcoma composed of squamous cell carcinoma with sarcomatous regions and true chondrosarcoma.

  12. Treatment of oral squamous cell carcinoma using anti-HER2 immunonanoshells

    Directory of Open Access Journals (Sweden)

    Fekrazad R

    2011-11-01

    Full Text Available Reza Fekrazad2, Neda Hakimiha3, Enice Farokhi3, Mohammad Javad Rasaee4, Mehdi Shafiee Ardestani5, Katayoun AM Kalhori2, Farzaneh Sheikholeslami1 1Research & Development Department, Production and Research Division of the Pasteur Institute of Iran, Karaj, Iran; 2Dental Department, AJA University of Medical Sciences, Laser Research Center, Dental Faculty, Tehran University of Medical Sciences; 3Dentistry Department, Faculty of Dentistry, Shahed University, Tehran, Iran; 4Department of Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 5Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran Background: Worldwide, oral squamous cell carcinoma (potentially mediated by HER2 is recognized as the most commonly occurring malignant neoplasm of the oral cavity. Anti-HER2 nanobodies conjugated to gold-silica nanoshells and used as photothermal treatment for oral squamous cell carcinoma may provide a novel therapeutic alternative to current treatment for this disease. Methods: KB epithelial or HeLaS3 cell cultures (controls were exposed to these immunonanoshells, and plasmon resonance electron initiation specific to gold was employed to burn the tumor cells. Results: Following this treatment, significant cell death occurred in the KB tumor cell cultures while there was no evidence of cellular damage or death in the HeLaS3 cell cultures. Conclusion: These findings suggest that photothermal treatment of oral squamous cell carcinoma has considerable advantages. Keywords: anti-HER2 immunonanoshells, gold-silica nanoshells, photothermal treatment, oral squamous cell carcinoma

  13. Sox9 drives columnar differentiation of esophageal squamous epithelium: a possible role in the pathogenesis of Barrett's esophagus.

    Science.gov (United States)

    Clemons, Nicholas J; Wang, David H; Croagh, Daniel; Tikoo, Anjali; Fennell, Christina M; Murone, Carmel; Scott, Andrew M; Watkins, D Neil; Phillips, Wayne A

    2012-12-15

    The molecular mechanism underlying the development of Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma, remains unknown. Our previous work implicated sonic hedgehog (Shh) signaling as a possible driver of BE and suggested that bone morphogenetic protein 4 (Bmp4) and Sox9 were downstream mediators. We have utilized a novel in vivo tissue reconstitution model to investigate the relative roles of Bmp4 and Sox9 in driving metaplasia. Epithelia reconstituted from squamous epithelial cells or empty vector-transduced cells had a stratified squamous phenotype, reminiscent of normal esophagus. Expression of Bmp4 in the stromal compartment activated signaling in the epithelium but did not alter the squamous phenotype. In contrast, expression of Sox9 in squamous epithelial cells induced formation of columnar-like epithelium with expression of the columnar differentiation marker cytokeratin 8 and the intestinal-specific glycoprotein A33. In patient tissue, A33 protein was expressed specifically in BE, but not in normal esophagus. Expression of Cdx2, another putative driver of BE, alone had no effect on reconstitution of a squamous epithelium. Furthermore, epithelium coexpressing Cdx2 and Sox9 had a phenotype similar to epithelium expressing Sox9 alone. Our results demonstrate that Sox9 is sufficient to drive columnar differentiation of squamous epithelium and expression of an intestinal differentiation marker, reminiscent of BE. These data suggest that Shh-mediated expression of Sox9 may be an important early event in the development of BE and that the potential for inhibitors of the hedgehog pathway to be used in the treatment of BE and/or esophageal adenocarcinoma could be tested in the near future.

  14. Holliday junction resolvases.

    Science.gov (United States)

    Wyatt, Haley D M; West, Stephen C

    2014-09-02

    Four-way DNA intermediates, called Holliday junctions (HJs), can form during meiotic and mitotic recombination, and their removal is crucial for chromosome segregation. A group of ubiquitous and highly specialized structure-selective endonucleases catalyze the cleavage of HJs into two disconnected DNA duplexes in a reaction called HJ resolution. These enzymes, called HJ resolvases, have been identified in bacteria and their bacteriophages, archaea, and eukaryotes. In this review, we discuss fundamental aspects of the HJ structure and their interaction with junction-resolving enzymes. This is followed by a brief discussion of the eubacterial RuvABC enzymes, which provide the paradigm for HJ resolvases in other organisms. Finally, we review the biochemical and structural properties of some well-characterized resolvases from archaea, bacteriophage, and eukaryotes. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  15. Wireless Josephson Junction Arrays

    Science.gov (United States)

    Adams, Laura

    2015-03-01

    We report low temperature, microwave transmission measurements on a wireless two- dimensional network of Josephson junction arrays composed of superconductor-insulator -superconductor tunnel junctions. Unlike their biased counterparts, by removing all electrical contacts to the arrays and superfluous microwave components and interconnects in the transmission line, we observe new collective behavior in the transmission spectra. In particular we will show emergent behavior that systematically responds to changes in microwave power at fixed temperature. Likewise we will show the dynamic and collective response of the arrays while tuning the temperature at fixed microwave power. We discuss these spectra in terms of the Berezinskii-Kosterlitz-Thouless phase transition and Shapiro steps. We gratefully acknowledge the support Prof. Steven Anlage at the University of Maryland and Prof. Allen Goldman at the University of Minnesota. Physics and School of Engineering and Applied Sciences.

  16. Eyelid Squamous Cell Carcinoma in a Dog

    OpenAIRE

    Chang-hyun Song1§, Sae-kwang Ku2§, Hwan-soo Jang3, Eun-young Kye, Sung-ho Yun, Kwang-ho Jang and Young-sam Kwon*

    2012-01-01

    A 10-year-old, female, Yorkshire Terrier was presented with a left lower eyelid mass. No other abnormality was detected on affected eye in a general eye examination. The mass was surgically removed and histologically diagnosed as a squamous cell carcinoma. The advancement flap used in this case may be an appropriate therapeutic choice for eyelid squamous cell carcinoma in dogs.

  17. Intracellular mediators of JAM-A-dependent epithelial barrier function.

    Science.gov (United States)

    Monteiro, Ana C; Parkos, Charles A

    2012-06-01

    Junctional adhesion molecule-A (JAM-A) is a critical signaling component of the apical junctional complex, a structure composed of several transmembrane and scaffold molecules that controls the passage of nutrients and solutes across epithelial surfaces. Observations from JAM-A-deficient epithelial cells and JAM-A knockout animals indicate that JAM-A is an important regulator of epithelial paracellular permeability; however, the mechanism(s) linking JAM-A to barrier function are not understood. This review highlights recent findings relevant to JAM-A-mediated regulation of epithelial permeability, focusing on the role of upstream and downstream signaling candidates. We draw on what is known about proteins reported to associate with JAM-A in other pathways and on known modulators of barrier function to propose candidate effectors that may mediate JAM-A regulation of epithelial paracellular permeability. Further investigation of pathways highlighted in this review may provide ideas for novel therapeutics that target debilitating conditions associated with barrier dysfunction, such as inflammatory bowel disease.

  18. Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components

    NARCIS (Netherlands)

    Ulluwishewa, D.; Anderson, R.C.; McNabb, W.C.; Moughan, P.J.; Wells, J.; Roy, N.C.

    2011-01-01

    The human intestinal epithelium is formed by a single layer of epithelial cells that separates the intestinal lumen from the underlying lamina propria. The space between these cells is sealed by tight junctions (TJ), which regulate the permeability of the intestinal barrier. TJ are complex protein s

  19. Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components

    NARCIS (Netherlands)

    Ulluwishewa, D.; Anderson, R.C.; McNabb, W.C.; Moughan, P.J.; Wells, J.; Roy, N.C.

    2011-01-01

    The human intestinal epithelium is formed by a single layer of epithelial cells that separates the intestinal lumen from the underlying lamina propria. The space between these cells is sealed by tight junctions (TJ), which regulate the permeability of the intestinal barrier. TJ are complex protein

  20. Interferon alpha-2a as alternative treatment for conjunctival squamous cell carcinoma.

    Science.gov (United States)

    Cruzado-Sánchez, D; Salas-Diaz, M; Tellez, W A; Alvarez-Matos, S E; Serpa-Frías, S

    2017-05-15

    A 35 year-old male patient with a history of HIV infection characterized by progressive tumour growth in bulbar conjunctiva of the left eye, corresponding to conjunctival squamous cell carcinoma that responded to treatment with interferon alpha-2a. Interferon alpha-2b has been used at conjunctival level as a topical immunomodulator treatment, with complete remission of epithelial neoplasms being observed. However, there have not been any previous publications on the use of interferon alpha-2a, which differs from interferon alpha-2b in a single amino acid, for the treatment of conjunctival squamous cell carcinoma. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Clear cell variant of squamous cell carcinoma of skin: A report of a case

    Directory of Open Access Journals (Sweden)

    Ahmed Oluwatoyin Lawal

    2013-01-01

    Full Text Available Clear cell squamous cell carcinoma (SCC is a rare variant of SCC of skin in which ultraviolet radiation has been suggested as possible etiology. This case is that of a 62-year-old male concrete block maker/bricklayer who presented with a 6 months history of a non-healing ulcer on the left side of his face. Histology showed features of malignant epithelial neoplasm composed of islands of large oval to polyhedral malignant squamous cells with eosinophilic to amphophilic cytoplasm and vesicular nuclei and there were areas showing clear cell differentiation and isolated areas of keratin pearl formation. The lesion was also negative for periodic acid schiff, mucicarmine, and alcian blue stains but was strongly positive for AE1/AE3 (immuno-stain. This case showed an aggressive and bizarre clinical presentation but more report of cases are needed to have a better characterization of the clinical presentation and prognosis of this variant of SCC.

  2. Clear cell variant of squamous cell carcinoma of skin: A report of a case.

    Science.gov (United States)

    Lawal, Ahmed Oluwatoyin; Adisa, Akinyele Olumuyiwa; Olajide, Mofoluwaso A; Olusanya, Adeola Adenike

    2013-01-01

    Clear cell squamous cell carcinoma (SCC) is a rare variant of SCC of skin in which ultraviolet radiation has been suggested as possible etiology. This case is that of a 62-year-old male concrete block maker/bricklayer who presented with a 6 months history of a non-healing ulcer on the left side of his face. Histology showed features of malignant epithelial neoplasm composed of islands of large oval to polyhedral malignant squamous cells with eosinophilic to amphophilic cytoplasm and vesicular nuclei and there were areas showing clear cell differentiation and isolated areas of keratin pearl formation. The lesion was also negative for periodic acid schiff, mucicarmine, and alcian blue stains but was strongly positive for AE1/AE3 (immuno-stain). This case showed an aggressive and bizarre clinical presentation but more report of cases are needed to have a better characterization of the clinical presentation and prognosis of this variant of SCC.

  3. Rac1 controls epithelial tube length through the apical secretion and polarity pathways

    Directory of Open Access Journals (Sweden)

    Kévin Sollier

    2016-01-01

    Full Text Available The morphometric parameters of epithelial tubes are critical to the physiology and homeostasis of most organs. In addition, many human diseases are associated with tube-size defects. Here, we show that Rac1 limits epithelial tube elongation in the developing fly trachea by promoting Rab5-dependent endocytosis of the apical determinant Crumbs. Rac1 is also involved in a positive feedback loop with the septate junction protein Coracle. Thereby, Rac1 precludes paracellular diffusion and contributes to the septate junction-dependent secretion of the chitin-modifying enzymes Vermiform and Serpentine, which restrict epithelial tube length independently of Crumbs. Thus, Rac1 is a critical component of two important pathways controlling epithelial tube morphogenesis.

  4. Rac1 controls epithelial tube length through the apical secretion and polarity pathways

    Science.gov (United States)

    Sollier, Kévin; Gaudé, Helori-Mael; Chartier, François J.-M.; Laprise, Patrick

    2016-01-01

    ABSTRACT The morphometric parameters of epithelial tubes are critical to the physiology and homeostasis of most organs. In addition, many human diseases are associated with tube-size defects. Here, we show that Rac1 limits epithelial tube elongation in the developing fly trachea by promoting Rab5-dependent endocytosis of the apical determinant Crumbs. Rac1 is also involved in a positive feedback loop with the septate junction protein Coracle. Thereby, Rac1 precludes paracellular diffusion and contributes to the septate junction-dependent secretion of the chitin-modifying enzymes Vermiform and Serpentine, which restrict epithelial tube length independently of Crumbs. Thus, Rac1 is a critical component of two important pathways controlling epithelial tube morphogenesis. PMID:26700724

  5. Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

    Science.gov (United States)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2016-03-01

    The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

  6. Nuclear factor κB and cyclooxygenase-2 immunoexpression in oral dysplasia and oral squamous cell carcinoma.

    Science.gov (United States)

    Pontes, Hélder Antônio Rebelo; Pontes, Flávia Sirotheau Corrêa; Fonseca, Felipe Paiva; de Carvalho, Pedro Luiz; Pereira, Erika Martins; de Abreu, Michelle Carvalho; de Freitas Silva, Brunno Santos; dos Santos Pinto, Décio

    2013-02-01

    Oral leukoplakia is the main potentially malignant oral lesion, and oral squamous cell carcinoma accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) proteins in dysplastic oral lesions and oral squamous cell carcinoma. Immunohistochemical reactions were performed on 6 inflammatory fibrous hyperplasia, 28 oral leukoplakia, and 15 oral squamous cell carcinoma paraffin-embedded samples. Immunoperoxidase reaction for NF-κB and COX-2 was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. Using the analysis of variance and the Tukey post hoc statistical analyses, a significantly increased immunoexpression for NF-κB was observed when oral squamous cell carcinoma samples were compared with the other groups studied. However, using the Kruskal-Wallis and the Dunn post hoc tests, a statistically significant result for COX-2 expression was obtained only when the moderate dysplasia group was compared with the inflammatory fibrous hyperplasia group. Nuclear factor κB may participate in the malignant phenotype acquisition process of the oral squamous cell carcinoma in its late stages, whereas COX-2 may be involved in the early stages of oral carcinogenesis process.

  7. Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases.

    Science.gov (United States)

    Banks, E R; Frierson, H F; Mills, S E; George, E; Zarbo, R J; Swanson, P E

    1992-10-01

    In this study of 40 cases of basaloid squamous cell carcinoma, 83% arose in the pyriform sinus, base of tongue, tonsil, and larynx. The 35 men and five women ranged in age from 27 to 88 years (median 62). In patients for whom social habits were recorded, 24 of 26 patients were smokers and 22 of 25 drank ethanol. Most presented with stage III or IV disease. Twenty-seven patients had regional metastases at the time of presentation and 15 developed distant metastases. Seventeen patients died with disease (median survival 18 months). The tumors were composed of moderately pleomorphic basaloid cells forming nests, cords, and frequent cribriform patterns. Squamous dysplasia of surface mucosa, focal squamous differentiation within invasive basaloid squamous cell carcinoma, or foci of conventional squamous cell carcinoma were present, alone or in combination. All studied neoplasms were immunohistochemically positive for keratins with the 34 beta E12 antibody. Approximately 80% were immunoreactive using AE1/AE3 or CAM 5.2. Epithelial membrane antigen, carcinoembryonic antigen, and S100 protein were found in 83%, 53%, and 39%, respectively, of the cases. Diffuse, weak immunoreactivity for neuron-specific enolase was seen in 75% of tumors. Synaptophysin, chromogranin, muscle-specific actin, and glial fibrillary acidic protein were absent. Basaloid squamous cell carcinoma has been confused with adenoid cystic carcinoma and small cell undifferentiated carcinoma, but is usually distinguishable in routine hematoxylin and eosin-stained sections, or, in rare problematic cases, with the aid of immunohistochemical studies. Distinction is warranted because the biologic behavior of basaloid squamous cell carcinoma differs from that of both of these lesions.

  8. The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Assia Hijazi

    Full Text Available BACKGROUND: Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. METHODOLOGY/PRINCIPAL FINDINGS: In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. CONCLUSION/SIGNIFICANCE: We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

  9. The PCP pathway regulates Baz planar distribution in epithelial cells

    OpenAIRE

    2016-01-01

    The localisation of apico-basal polarity proteins along the Z-axis of epithelial cells is well understood while their distribution in the plane of the epithelium is poorly characterised. Here we provide a systematic description of the planar localisation of apico-basal polarity proteins in the Drosophila ommatidial epithelium. We show that the adherens junction proteins Shotgun and Armadillo, as well as the baso-lateral complexes, are bilateral, i.e. present on both sides of cell interfaces. ...

  10. "Targeted disruption of the epithelial-barrier by Helicobacter pylori"

    Directory of Open Access Journals (Sweden)

    Wroblewski Lydia E

    2011-11-01

    Full Text Available Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier.

  11. Alveolocapillary model system to study alveolar re-epithelialization

    Energy Technology Data Exchange (ETDEWEB)

    Willems, Coen H.M.P.; Zimmermann, Luc J.I.; Sanders, Patricia J.L.T.; Wagendorp, Margot; Kloosterboer, Nico [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands); Cohen Tervaert, Jan Willem [Division of Clinical and Experimental Immunology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht (Netherlands); Duimel, Hans J.Q.; Verheyen, Fons K.C.P. [Electron Microscopy Unit, Department of Molecular Cell Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Iwaarden, J. Freek van, E-mail: f.vaniwaarden@maastrichtuniversity.nl [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands)

    2013-01-01

    In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process. -- Highlights: ► Model system for vital imaging and high throughput screening. ► Microvascular endothelium influences re-epithelialization. ► A549 cells form protrusions through membrane to contact HPMEC. ► A549 cells and HPMECs form heterocellular tight-, gap- and adherens-junctions.

  12. Squamous cell cancer of the rectum

    Institute of Scientific and Technical Information of China (English)

    Tara Dyson; Peter V Draganov

    2009-01-01

    Squamous cell carcinoma of the rectum is a rare malignancy. It appears to be associated with chronic inflammatory conditions and infections. The clear association seen between Human Papilloma Virus and various squamous cancers has not been firmly established for the squamous cell cancer of the rectum. The presentation is nonspecific and patients tend to present with advanced stage disease. Diagnosis relies on endoscopic examination with biopsy of the lesion. Distinction from squamous cell cancer of the anus can be difficult, but can be facilitated by immunohistochemical staining for cytokeratins. Staging of the cancer with endoscopic ultrasound and computed tomography provides essential information on prognosis and can guide therapy. At present, surgery remains the main therapeutic option; however recent advances have made chemoradiation a valuable therapeutic addition. Squamous cell carcinoma of the rectum is a distinct entity and it is of crucial importance for the practicing Gastroenterologist to be thoroughly familiar with this disease. Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal, squamous cell carcinoma of the rectum has different epidemiology, etiology, pathogenesis, and prognosis but, most importantly, requires a different therapeutic approach. This review will examine and summarize the available information regarding this disease from the perspective of the practicing gastroenterologist.

  13. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    Science.gov (United States)

    2016-12-19

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

  14. An induced junction photovoltaic cell

    Science.gov (United States)

    Call, R. L.

    1974-01-01

    Silicon solar cells operating with induced junctions rather than diffused junctions have been fabricated and tested. Induced junctions were created by forming an inversion layer near the surface of the silicon by supplying a sheet of positive charge above the surface. Measurements of the response of the inversion layer cell to light of different wavelengths indicated it to be more sensitive to the shorter wavelengths of the sun's spectrum than conventional cells. The greater sensitivity occurs because of the shallow junction and the strong electric field at the surface.

  15. Microbial products induce claudin-2 to compromise gut epithelial barrier function.

    Directory of Open Access Journals (Sweden)

    Xiaoyu Liu

    Full Text Available The epithelial barrier dysfunction is an important pathogenic feature in a number of diseases. The underlying mechanism is to be further investigated. The present study aims to investigate the role of tight junction protein claudin-2 (Cldn2 in the compromising epithelial barrier function. In this study, the expression of Cldn2 in the epithelial layer of mice and patients with food allergy was observed by immunohistochemistry. The induction of Cldn2 was carried out with a cell culture model. The Cldn2-facilitated antigen internalization was observed by confocal microscopy. The epithelial barrier function in the gut epithelial monolayer was assessed by recording the transepithelial resistance and assessing the permeability to a macromolecular tracer. The results showed that the positive immune staining of Cldn2 was observed in the epithelial layer of the small intestine that was weakly stained in naïve control mice, and strongly stained in sensitized mice as well as patients with food allergy. Exposure to cholera toxin or Staphylococcal enterotoxin B induced the expression of Cldn2 in HT-29 or T84 cells. Cldn2 could bind protein antigen to form complexes to facilitate the antigen transport across the epithelial barrier. Blocking Cldn2 prevented the allergen-related hypersensitivity the intestine. We conclude that the tight junction protein Cldn2 is involved in the epithelial barrier dysfunction.

  16. New Developments in Ocular Surface Squamous Neoplasia

    Directory of Open Access Journals (Sweden)

    Ayşe Yağcı

    2014-09-01

    Full Text Available Ocular surface squamous neoplasia originates from conjunctiva epithelium and covers a broad spectrum of disease ranging from dysplasia to squamous cell carcinoma. Clinical features may vary from case to case. Traditional treatment of excision with no-touch technique combined with adjuvant therapies because of high recurrence rate. Main adjuvant treatments are cryotherapy and chemotherapy. In this review, clinical forms, differential diagnosis, American Joint Committee on Cancer classification and recent approaches to the management of ocular surface squamous dysplasia were described. (Turk J Ophthalmol 2014; 44: Supplement 8-14

  17. ACANTHOLYTIC SQUAMOUS CELL CARCINOMA OF PREPUCE

    Directory of Open Access Journals (Sweden)

    Mamina

    2014-03-01

    Full Text Available An uncircumcised 65 year male, with history of phimosis presented with retention of urine and ulceration and bleeding in the prepuce. Circumcision was done under local anesthesia which revealed an ulcero-proliferative growth involving the prepuce and glans. The prepucial skin was sent for histopathological examination. The diagnosis was histopathologically confirmed as Acantholytic Squamous Cell Carcinoma. Acantholytic squamous cell carcinoma is a highly malignant, unusual variant of squamous cell carcinoma invading deeper anatomic structures and is associated with a higher incidence of regional metastasis and mortality.

  18. Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas.

    Science.gov (United States)

    Shahrabi-Farahani, Shokoufeh; Wang, Lili; Zwaans, Bernadette M M; Santana, Jeans M; Shimizu, Akio; Takashima, Seiji; Kreuter, Michael; Coultas, Leigh; D'Amore, Patricia A; Arbeit, Jeffrey M; Akslen, Lars A; Bielenberg, Diane R

    2014-07-01

    Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did co-localize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or epidermal growth factor-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity.

  19. Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Wusheng

    2012-01-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC, the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB, normal differentiated squamous epithelium (ND, and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and

  20. Barret's adenocarcinomas resemble adenocarcinomas of the gastric cardia in terms of chromosomal copy number changes, but relate to squamous cell carcinomas of the distal oesophagus with respect to the presence of high-level amplifications

    NARCIS (Netherlands)

    M.M. Weiss (Marjan); E.J. Kuipers (Ernst); M.A.J.A. Hermsen (Mario); N.C.T. Grieken (Nicole); G.J.A. Offerhaus (Johan); J.P.A. Baak (Jan); S.G.M. Meuwissen; C.J.L.M. Meijer (Chris)

    2003-01-01

    textabstractThree different cancers predominantly occur at the gastro-oesophageal junction: squamous cell carcinomas of the distal oesophagus, adenocarcinomas of the distal oesophagus (Barrett's carcinomas), and adenocarcinomas of the gastric cardia. The aim of the present study was to investigate

  1. AKT primes snail-induced EMT concomitantly with the collective migration of squamous cell carcinoma cells.

    Science.gov (United States)

    Okui, Gaku; Tobiume, Kei; Rizqiawan, Andra; Yamamoto, Kazuhiro; Shigeishi, Hideo; Ono, Shigehiro; Higashikawa, Koichiro; Kamata, Nobuyuki

    2013-09-01

    In this study, we found that wounding of a confluent monolayer of squamous cell carcinoma (SCC) cells induced epithelial-mesenchymal transition (EMT) specifically at the edge of the wound. This process required the combined stimulation of TGFβ, TNFα, and PDGF-D. Such a combined cytokine treatment of confluent monolayers of the cells upregulated the expression levels of Snail and Slug via PI3K. The PI3K downstream effector, AKT, was dispensable for the upregulation of Snail and Slug, but essential for enabling EMT in response to upregulation of Snail and Slug. Copyright © 2013 Wiley Periodicals, Inc.

  2. Mixing in T-junctions

    NARCIS (Netherlands)

    Kok, Jacobus B.W.; van der Wal, S.

    1996-01-01

    The transport processes that are involved in the mixing of two gases in a T-junction mixer are investigated. The turbulent flow field is calculated for the T-junction with the k- turbulence model by FLOW3D. In the mathematical model the transport of species is described with a mixture fraction

  3. Influence of the intrinsic gut microbiota on transcriptional regulation of genes involved in the early life development of intestinal epithelial integrity

    DEFF Research Database (Denmark)

    Bergström, Anders; Kristensen, Matilde Bylov; Frøkjær, Hanne

    surfaces of all epithelial linings by physical or specific hindrance of pathogenic species e.g. virus and bacteria. Moreover, the proteins constituting the tight junctions in the apical membrane of the epithelial cells are important as they take part in controlling, which substances can penetrate...

  4. Influence of the intrinsic gut microbiota on transcriptional regulation of genes involved in the early life development of intestinal epithelial integrity

    DEFF Research Database (Denmark)

    Bergström, Anders; Kristensen, Matilde Bylov; Frøkjær, Hanne

    2010-01-01

    surfaces of all epithelial linings by physical or specific hindrance of pathogenic species e.g. virus and bacteria. Moreover, the proteins constituting the tight junctions in the apical membrane of the epithelial cells are important as they take part in controlling, which substances can penetrate...

  5. Eyelid Squamous Cell Carcinoma in a Dog

    Directory of Open Access Journals (Sweden)

    Chang-hyun Song1§, Sae-kwang Ku2§, Hwan-soo Jang3, Eun-young Kye, Sung-ho Yun, Kwang-ho Jang and Young-sam Kwon*

    2012-06-01

    Full Text Available A 10-year-old, female, Yorkshire Terrier was presented with a left lower eyelid mass. No other abnormality was detected on affected eye in a general eye examination. The mass was surgically removed and histologically diagnosed as a squamous cell carcinoma. The advancement flap used in this case may be an appropriate therapeutic choice for eyelid squamous cell carcinoma in dogs.

  6. Diffuse optical microscopy for quantification of depth-dependent epithelial backscattering in the cervix

    Science.gov (United States)

    Bodenschatz, Nico; Lam, Sylvia; Carraro, Anita; Korbelik, Jagoda; Miller, Dianne M.; McAlpine, Jessica N.; Lee, Marette; Kienle, Alwin; MacAulay, Calum

    2016-06-01

    A fiber optic imaging approach is presented using structured illumination for quantification of almost pure epithelial backscattering. We employ multiple spatially modulated projection patterns and camera-based reflectance capture to image depth-dependent epithelial scattering. The potential diagnostic value of our approach is investigated on cervical ex vivo tissue specimens. Our study indicates a strong backscattering increase in the upper part of the cervical epithelium caused by dysplastic microstructural changes. Quantization of relative depth-dependent backscattering is confirmed as a potentially useful diagnostic feature for detection of precancerous lesions in cervical squamous epithelium.

  7. Re-epithelializaiton by epithelial inoculation with recipient phenotype in heterotopically transplanted rat allografts

    Institute of Scientific and Technical Information of China (English)

    Zheng Hui; Hu Xuefei; Li Chao; Xie Huikang; Gao Wen; Chen Chang

    2014-01-01

    Background Re-epithelialization has remained a major obstacle in both tracheal and lung transplantations.This study examines the realization of re-epithelialization by epithelial inoculation in a rat heterotopic tracheal transplantation model.Methods The original epithelia of tracheas from donor Wistar rats were removed and the tracheas were then inoculated with 106/ml in vitro cultured epithelial cells of the Spraque-Dawley (SD) rat phenotype.These allo-tracheas were then heterotopically transplanted into SD rats.After 28 days,the allo-trachea tissues were recovered and assessed for epithelial morphology and cellular differentiation using immunohistochemical analysis.An additional experimental group was used to compare the outcomes of re-epithelialization in immunosuppressed animals.Results Histological examination showed that allografts with epithelial inoculation maintained patent tracheal lumens,which were obliterated in controls.Recipient immunosuppression facilitated the formation of an integrated ciliated epithelial layer,further demonstrated by the presence of a dense cilia population,a well-developed plasma membrane,and readily recognizable intercellular junctions.Epithelial cellular differentiation markers such as cytokeratin 14 and 18,and cystic fibrosis transmembrane conductance regulator (CFTR) were all positive in allografts under immunosuppression.Conclusion Concurrent recipient-derived epithelial inoculation with immunosuppression can result in complete reepithelialization with the recipient phenotype and suppress the luminal obliteration process in heterotopic transplantations.

  8. [Focal epithelial hyperplasia].

    Science.gov (United States)

    Vera-Iglesias, E; García-Arpa, M; Sánchez-Caminero, P; Romero-Aguilera, G; Cortina de la Calle, P

    2007-11-01

    Focal epithelial hyperplasia is a rare disease of the oral mucosa caused by the human papilloma virus (HPV). It appears as a benign epithelial growth, usually in the mucosa of the lower lip. It is mainly associated with HPV serotypes 13 and 32 and there is a clear racial predilection for the disease in Native Americans and Eskimos. We describe the case of a 17-year-old girl from Ecuador with multiple papular lesions in both lips that were clinically and histologically consistent with focal epithelial hyperplasia. Analysis by polymerase chain reaction detected HPV serotype 13.

  9. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Jacob Barbara A

    2009-02-01

    Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

  10. Gene expression correlations in human cancer cell lines define molecular interaction networks for epithelial phenotype.

    Directory of Open Access Journals (Sweden)

    Kurt W Kohn

    Full Text Available Using gene expression data to enhance our knowledge of control networks relevant to cancer biology and therapy is a challenging but urgent task. Based on the premise that genes that are expressed together in a variety of cell types are likely to functions together, we derived mutually correlated genes that function together in various processes in epithelial-like tumor cells. Expression-correlated genes were derived from data for the NCI-60 human tumor cell lines, as well as data from the Broad Institute's CCLE cell lines. NCI-60 cell lines that selectively expressed a mutually correlated subset of tight junction genes served as a signature for epithelial-like cancer cells. Those signature cell lines served as a seed to derive other correlated genes, many of which had various other epithelial-related functions. Literature survey yielded molecular interaction and function information about those genes, from which molecular interaction maps were assembled. Many of the genes had epithelial functions unrelated to tight junctions, demonstrating that new function categories were elicited. The most highly correlated genes were implicated in the following epithelial functions: interactions at tight junctions (CLDN7, CLDN4, CLDN3, MARVELD3, MARVELD2, TJP3, CGN, CRB3, LLGL2, EPCAM, LNX1; interactions at adherens junctions (CDH1, ADAP1, CAMSAP3; interactions at desmosomes (PPL, PKP3, JUP; transcription regulation of cell-cell junction complexes (GRHL1 and 2; epithelial RNA splicing regulators (ESRP1 and 2; epithelial vesicle traffic (RAB25, EPN3, GRHL2, EHF, ADAP1, MYO5B; epithelial Ca(+2 signaling (ATP2C2, S100A14, BSPRY; terminal differentiation of epithelial cells (OVOL1 and 2, ST14, PRSS8, SPINT1 and 2; maintenance of apico-basal polarity (RAB25, LLGL2, EPN3. The findings provide a foundation for future studies to elucidate the functions of regulatory networks specific to epithelial-like cancer cells and to probe for anti-cancer drug targets.

  11. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease.

    Science.gov (United States)

    Lerner, Aaron; Matthias, Torsten

    2015-06-01

    The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression.

  12. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    Science.gov (United States)

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Airway Epithelial Barrier Dysfunction in COPD: Role of Cigarette Smoke Exposure.

    Science.gov (United States)

    Aghapour, Mahyar; Raee, Pourya; Moghaddam, Seyed Javad; Hiemstra, Pieter S; Heijink, Irene H

    2017-09-21

    The epithelial lining of the airway forms the first barrier against environmental insults such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair and pro-inflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to re-differentiate into a functionally intact epithelium.

  14. Metallic Junction Thermoelectric Device Simulations

    Science.gov (United States)

    Duzik, Adam J.; Choi, Sang H.

    2017-01-01

    Thermoelectric junctions made of semiconductors have existed in radioisotope thermoelectric generators (RTG) for deep space missions, but are currently being adapted for terrestrial energy harvesting. Unfortunately, these devices are inefficient, operating at only 7% efficiency. This low efficiency has driven efforts to make high-figure-of-merit thermoelectric devices, which require a high electrical conductivity but a low thermal conductivity, a combination that is difficult to achieve. Lowered thermal conductivity has increased efficiency, but at the cost of power output. An alternative setup is to use metallic junctions rather than semiconductors as thermoelectric devices. Metals have orders of magnitude more electrons and electronic conductivities higher than semiconductors, but thermal conductivity is higher as well. To evaluate the viability of metallic junction thermoelectrics, a two dimensional heat transfer MATLAB simulation was constructed to calculate efficiency and power output. High Seebeck coefficient alloys, Chromel (90%Ni-10%Cr) and Constantan (55%Cu-45%Ni), produced efficiencies of around 20-30%. Parameters such as the number of layers of junctions, lateral junction density, and junction sizes for both series- and parallel-connected junctions were explored.

  15. Girdin-mediated interactions between cadherin and the actin cytoskeleton are required for epithelial morphogenesis in Drosophila.

    Science.gov (United States)

    Houssin, Elise; Tepass, Ulrich; Laprise, Patrick

    2015-05-15

    E-cadherin-mediated cell-cell adhesion is fundamental for epithelial tissue morphogenesis, physiology and repair. E-cadherin is a core transmembrane constituent of the zonula adherens (ZA), a belt-like adherens junction located at the apicolateral border in epithelial cells. The anchorage of ZA components to cortical actin filaments strengthens cell-cell cohesion and allows for junction contractility, which shapes epithelial tissues during development. Here, we report that the cytoskeletal adaptor protein Girdin physically and functionally interacts with components of the cadherin-catenin complex during Drosophila embryogenesis. Fly Girdin is broadly expressed throughout embryonic development and enriched at the ZA in epithelial tissues. Girdin associates with the cytoskeleton and co-precipitates with the cadherin-catenin complex protein α-Catenin (α-Cat). Girdin mutations strongly enhance adhesion defects associated with reduced DE-cadherin (DE-Cad) expression. Moreover, the fraction of DE-Cad molecules associated with the cytoskeleton decreases in the absence of Girdin, thereby identifying Girdin as a positive regulator of adherens junction function. Girdin mutant embryos display isolated epithelial cell cysts and rupture of the ventral midline, consistent with defects in cell-cell cohesion. In addition, loss of Girdin impairs the collective migration of epithelial cells, resulting in dorsal closure defects. We propose that Girdin stabilizes epithelial cell adhesion and promotes morphogenesis by regulating the linkage of the cadherin-catenin complex to the cytoskeleton.

  16. Cross-talk between intestinal epithelial cells and immune cells in inflammatory bowel disease.

    Science.gov (United States)

    Al-Ghadban, Sara; Kaissi, Samira; Homaidan, Fadia R; Naim, Hassan Y; El-Sabban, Marwan E

    2016-07-15

    Inflammatory bowel disease (IBD) involves functional impairment of intestinal epithelial cells (IECs), concomitant with the infiltration of the lamina propria by inflammatory cells. We explored the reciprocal paracrine and direct interaction between human IECs and macrophages (MΦ) in a co-culture system that mimics some aspects of IBD. We investigated the expression of intercellular junctional proteins in cultured IECs under inflammatory conditions and in tissues from IBD patients. IECs establish functional gap junctions with IECs and MΦ, respectively. Connexin (Cx26) and Cx43 expression in cultured IECs is augmented under inflammatory conditions; while, Cx43-associated junctional complexes partners, E-cadherin, ZO-1, and β-catenin expression is decreased. The expression of Cx26 and Cx43 in IBD tissues is redistributed to the basal membrane of IEC, which is associated with decrease in junctional complex proteins' expression, collagen type IV expression and infiltration of MΦ. These data support the notion that the combination of paracrine and hetero-cellular communication between IECs and MΦs may regulate epithelial cell function through the establishment of junctional complexes between inflammatory cells and IECs, which ultimately contribute to the dys-regulation of intestinal epithelial barrier.

  17. Cross-talk between intestinal epithelial cells and immune cells in inflammatory bowel disease

    Science.gov (United States)

    Al-Ghadban, Sara; Kaissi, Samira; Homaidan, Fadia R.; Naim, Hassan Y.; El-Sabban, Marwan E.

    2016-01-01

    Inflammatory bowel disease (IBD) involves functional impairment of intestinal epithelial cells (IECs), concomitant with the infiltration of the lamina propria by inflammatory cells. We explored the reciprocal paracrine and direct interaction between human IECs and macrophages (MΦ) in a co-culture system that mimics some aspects of IBD. We investigated the expression of intercellular junctional proteins in cultured IECs under inflammatory conditions and in tissues from IBD patients. IECs establish functional gap junctions with IECs and MΦ, respectively. Connexin (Cx26) and Cx43 expression in cultured IECs is augmented under inflammatory conditions; while, Cx43-associated junctional complexes partners, E-cadherin, ZO-1, and β-catenin expression is decreased. The expression of Cx26 and Cx43 in IBD tissues is redistributed to the basal membrane of IEC, which is associated with decrease in junctional complex proteins’ expression, collagen type IV expression and infiltration of MΦ. These data support the notion that the combination of paracrine and hetero-cellular communication between IECs and MΦs may regulate epithelial cell function through the establishment of junctional complexes between inflammatory cells and IECs, which ultimately contribute to the dys-regulation of intestinal epithelial barrier. PMID:27417573

  18. [A bilateral epithelial myoepithelial carcinoma of the parotid gland].

    Science.gov (United States)

    Tauziède-Espariat, Arnault; Raffoul, Johnny; Sun, Shan Rong; Monnin, Christine; Lassabe, Catherine; Costes, Valérie

    2015-12-01

    We report the case of a 52-year-old man, who was admitted in the department of otorhinolaryngology for a mass of the right parotid gland. The radiological and clinical hypothesis was a squamous cell carcinoma. Histopathological examination revealed a biphasic proliferation composed of epithelial cells arranged in a tubular pattern stained with cytokeratins 5-6 and 7 and EMA surrounded by clear myoepithelial cells stained with smooth muscle actin and p63. Ki-67 labeling index was low. The diagnosis of epithelial myoepithelial carcinoma was proposed. One year after, the patient noticed a centimetric mass of the left parotid gland. The radiological hypothesis was the presence of an intraparotidian lymph node. Histopathological examination showed a second epithelial myoepithelial carcinoma. This is an uncommon neoplasm comprising approximately 1% of all salivary gland tumours, affecting mainly the parotid gland. It is occurring preferably in patients older than 60years old. This is a low-grade malignant tumour with tendency to local recurrence and lymph node metastatic potential. We describe an exceptional bilateral epithelial myoepithelial carcinoma of the parotid gland.

  19. 'See and treat' approach for high-grade squamous intraepithelial cervical lesions.

    Science.gov (United States)

    Nooij, L S; Kagie, M J

    2016-01-01

    Evaluation of the over-treatment percentage when choosing a 'see and treat' approach in patients with de- viant cervical smear test results. The authors performed a retrospective chart review among women who were treated for cytological low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL) from January 2009 until December 2010. All patients who were treated for deviant Pap-smears were analyzed. Patient characteristics were taken into account when performing the analysis. Data were analyzed using SPSS. Logistic regression was performed to determine the influence of age, smoking, and the reason to perform the Pap-smear. A total of 723 patients with deviant Pap-smear results were analysed. High-grade cervical intraepithelial neoplasia (CIN) was found in 70.3% of the patients with a Pap 3A average dysplasia (low-grade squamous intraepithelial lesion). This indicates that 29.7% of the patients would be over-treated with a 'see and treat' approach. For Pap 3B (high-grade intra-epithelial lesion) or higher the over-treatment percentage was 6.7% or less. Potential risks of a loop electrosurgical excision procedure (LEEP) on future pregnancies and fertility should be taken into account when treating fertile patients for potential CIN. This should be part of the counseling process of patients with a Pap 3A average dysplasia. A 'see and treat' approach can and probably should be proposed to patients with a Pap 3B or higher.

  20. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma

    Science.gov (United States)

    Zhang, Hongfang; Luo, Honglei; Jiang, Zhenzhen; Yue, Jing; Hou, Qiang; Xie, Ruifei; Wu, Shixiu

    2016-01-01

    The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy. PMID:27125498

  1. Epidemiology of Cervical Squamous Intraepithelial Lesions in HIV ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    increased risk of prevalence, incidence, and persistent squamous ... using the Visual Inspection with Lugol's Iodine ..... Deficiency Syndrome 1999, 21:33-41. 3. Massad LS AL ... and risk factors for cervical squamous intraepithelial lesions ...

  2. PREVALENCE OF AGE, GENDER AND TYPE OF GASTRO OESOPHAGEAL JUNCTION MALIGNANCY IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Jithin Eldo

    2016-03-01

    Full Text Available BACKGROUND Cancer of the oesophagus is the ninth most common malignancy, causes 2% of all cancer-related deaths worldwide. This study was aimed to determine the type of malignancy more common in gastro oesophageal junction as well as to know the age and gender distribution of malignancy. METHODS Longitudinal study was done by including all the diagnosed cases of carcinoma of gastro oesophageal junction who had undergone oesophagectomy. The resected specimen of the subset of patients with adenocarcinoma was examined for the presence of intestinal metaplasia using haematoxylin and eosin stain. RESULTS A total of 36 patients were studied. Among the 36 cases, 21 cases (58.33% were squamous cell carcinoma with 13 patients (61.9% between 50 years and 70 years of age and rest 15 cases (41.66% were adenocarcinoma with 8 patients (53.3% between 50 to 60 years of age. All the adenocarcinomas were presented in late stage (T3 or T4, 60% with lymph node metastasis and 20% of patients had intestinal metaplasia. Among the patients with squamous cell carcinoma, 62% presented with T3 disease and 33% presented with T2 disease and only 19% of patients had lymph node metastasis. CONCLUSION Among the malignancy at the gastro oesophageal junction, squamous cell carcinoma with female dominance was more common than adenocarcinoma with male dominance. Most of the cases were with well differentiated tumours presenting at a late stage of the disease either T3 or T4 with low incidence of lymph node metastasis. Adenocarcinoma showed a low incidence of specialized intestinal metaplasia.

  3. Imaging of cervicothoracic junction trauma

    Directory of Open Access Journals (Sweden)

    Wongwaisayawan S

    2013-01-01

    Full Text Available Sirote Wongwaisayawan,1 Ruedeekorn Suwannanon,2 Rathachai Kaewlai11Department of Radiology, Ramathibodi Hospital and Mahidol University, Bangkok, Thailand; 2Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, ThailandAbstract: Cervicothoracic junction trauma is an important cause of morbidity and mortality in trauma patients. Imaging has played an important role in identifying injuries and guiding appropriate, timely therapy. Computed tomography is currently a method of choice for diagnosing cervicothoracic junction trauma, in which the pattern of injuries often suggests possible mechanisms and potential injuries. In this article, the authors describe and illustrate common and uncommon injuries that can occur in the cervicothoracic junction.Keywords: cervicothoracic junction, cervical spine, trauma, imaging, radiology

  4. Establishment of Epithelial Attachment on Titanium Surface Coated with Platelet Activating Peptide

    Science.gov (United States)

    Sugawara, Shiho; Maeno, Masahiko; Lee, Cliff; Nagai, Shigemi; Kim, David M.; Da Silva, John; Kondo, Hisatomo

    2016-01-01

    The aim of this study was to produce epithelial attachment on a typical implant abutment surface of smooth titanium. A challenging complication that hinders the success of dental implants is peri-implantitis. A common cause of peri-implantitis may results from the lack of epithelial sealing at the peri-implant collar. Histologically, epithelial sealing is recognized as the attachment of the basement membrane (BM). BM-attachment is promoted by activated platelet aggregates at surgical wound sites. On the other hand, platelets did not aggregate on smooth titanium, the surface typical of the implant abutment. We then hypothesized that epithelial BM-attachment was produced when titanium surface was modified to allow platelet aggregation. Titanium surfaces were coated with a protease activated receptor 4-activating peptide (PAR4-AP). PAR4-AP coating yielded rapid aggregation of platelets on the titanium surface. Platelet aggregates released robust amount of epithelial chemoattractants (IGF-I, TGF-β) and growth factors (EGF, VEGF) on the titanium surface. Human gingival epithelial cells, when they were co-cultured on the platelet aggregates, successfully attached to the PAR4-AP coated titanium surface with spread laminin5 positive BM and consecutive staining of the epithelial tight junction component ZO1, indicating the formation of complete epithelial sheet. These in-vitro results indicate the establishment of epithelial BM-attachment to the titanium surface. PMID:27741287

  5. Roles of Wnt/{beta}-catenin signaling in epithelial differentiation of mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yajing; Sun, Zhaorui; Qiu, Xuefeng [Immunology and Reproductive Biology Laboratory, Medical College of Nanjing University, Nanjing 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093 (China); Li, Yan [Jiangsu Centers for Diseases Prevention and Control, Nanjing 210009 (China); Qin, Jizheng [Immunology and Reproductive Biology Laboratory, Medical College of Nanjing University, Nanjing 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093 (China); Han, Xiaodong, E-mail: hanxd@nju.edu.cn [Immunology and Reproductive Biology Laboratory, Medical College of Nanjing University, Nanjing 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093 (China)

    2009-12-25

    Bone marrow-derived mesenchymal stem cells (MSCs) have been demonstrated to be able to differentiate into epithelial lineage, but the precise mechanisms controlling this process are unclear. Our aim is to explore the roles of Wnt/{beta}-catenin in the epithelial differentiation of MSCs. Using indirect co-culture of rat MSCs with rat airway epithelial cells (RTE), MSCs expressed several airway epithelial markers (cytokeratin 18, tight junction protein occudin, cystic fibrosis transmembrance regulator). The protein levels of some important members in Wnt/{beta}-catenin signaling were determined, suggested down-regulation of Wnt/{beta}-catenin with epithelial differentiation of MSCs. Furthermore, Wnt3{alpha} can inhibit the epithelial differentiation of MSCs. A loss of {beta}-catenin induced by Dickkopf-1 can enhance MSCs differentiation into epithelial cells. Lithium chloride transiently activated {beta}-catenin expression and subsequently decreased {beta}-catenin level and at last inhibited MSCs to differentiate into airway epithelium. Taken together, our study indicated that RTE cells can trigger epithelial differentiation of MSCs. Blocking Wnt/{beta}-catenin signaling may promote MSCs to differentiate towards airway epithelial cells.

  6. Demonstrated Anomalous Pancreaticobiliary Ductal Junction

    OpenAIRE

    Koçkar, Cem; ?ENOL, Altu?; BA?TÜRK, Abdulkadir; AYDIN, Bünyamin; Cüre, Erkan

    2015-01-01

    Anomalies of the pancreaticobiliary junction are rare. Clinically anomalies of the pancreaticobiliary junction are uncommonly symptomatic but may present themselves with associated conditions ranging from benign acute abdominal pain to carcinomas. A 52 years old man was admitted to gastroenterology service with complaints of fever, nausea, vomiting and recurrent epigastric pain. He was diagnosed with biliary pancreatitis. Endoscopic retrograde cholangiopancreato-graphy was performed. Papilla ...

  7. Josephson junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Wild, Georg Hermann

    2012-03-04

    We report on the fabrication of superconductor/insulator/ferromagnetic metal/superconductor (Nb/AlO{sub x}/Pd{sub 0.82}Ni{sub 0.18}/Nb) Josephson junctions (SIFS JJs) with high critical current densities, large normal resistance times area products, and high quality factors. For these junctions, a transition from 0- to {pi}-coupling is observed for a thickness d{sub F}=6 nm of the ferromagnetic Pd{sub 0.82}Ni{sub 0.18} interlayer. The magnetic field dependence of the critical current of the junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd{sub 0.82}Ni{sub 0.18} has an out-of-plane anisotropy and large saturation magnetization indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes up to about 400 GHz provides valuable information on the junction quality factor and the relevant damping mechanisms. Whereas losses due to quasiparticle tunneling dominate at low frequencies, at high frequencies the damping is explained by the finite surface resistance of the junction electrodes. High quality factors of up to 30 around 200 GHz have been achieved. They allow to study the junction dynamics, in particular the switching probability from the zero-voltage into the voltage state with and without microwave irradiation. The experiments with microwave irradiation are well explained within semi-classical models and numerical simulations. In contrast, at mK temperature the switching dynamics without applied microwaves clearly shows secondary quantum effects. Here, we could observe for the first time macroscopic quantum tunneling in Josephson junctions with a ferromagnetic interlayer. This observation excludes fluctuations of the critical current as a consequence of an unstable magnetic domain structure of the ferromagnetic interlayer and affirms the suitability of SIFS Josephson junctions for quantum information processing.

  8. Cytomorphological evaluation of squamous cell abnormalities observed on cervical smears in government medical college, Jabalpur, India: a five year study

    Directory of Open Access Journals (Sweden)

    Radhika Rajesh Nandwani

    2016-03-01

    Results: The overall frequency of normal, inadequate, inflammatory, and abnormal smears was 11.86%, 5.73%, 74.98% and 13.2% respectively. Atypical squamous cell carcinoma of undermined significance (ASCUS was seen in 3.61%, squamous intraepithelial lesion (SIL was seen in 5.36%, low grade squamous intraepithelial lesion (LSIL was seen in 2.59% while high grade squamous intraepithelial lesion (HSIL was seen in 2.77%. Invasive carcinoma was seen in 3.69%. The premalignant epithelial abnormalities like ASCUS, LSIL and HSIL were found to be highest in the age group of 31-50 years in our study, which correlated well with other similar studies. Conclusions: Hence we should advocate regular cervical cytology (PAP smear study, which can help to treat cervix lesions early before the progress into cervical cancer. Early detection is the only key to saving a woman's life as the later the abnormalities are discovered; mortality, morbidity and treatment cost all increase. [Int J Res Med Sci 2016; 4(3.000: 794-799

  9. Electronic thermometry in tunable tunnel junction

    Energy Technology Data Exchange (ETDEWEB)

    Maksymovych, Petro

    2016-03-15

    A tunable tunnel junction thermometry circuit includes a variable width tunnel junction between a test object and a probe. The junction width is varied and a change in thermovoltage across the junction with respect to the change in distance across the junction is determined. Also, a change in biased current with respect to a change in distance across the junction is determined. A temperature gradient across the junction is determined based on a mathematical relationship between the temperature gradient, the change in thermovoltage with respect to distance and the change in biased current with respect to distance. Thermovoltage may be measured by nullifying a thermoelectric tunneling current with an applied voltage supply level. A piezoelectric actuator may modulate the probe, and thus the junction width, to vary thermovoltage and biased current across the junction. Lock-in amplifiers measure the derivatives of the thermovoltage and biased current modulated by varying junction width.

  10. Confocal Annular Josephson Tunnel Junctions

    Science.gov (United States)

    Monaco, Roberto

    2016-09-01

    The physics of Josephson tunnel junctions drastically depends on their geometrical configurations and here we show that also tiny geometrical details play a determinant role. More specifically, we develop the theory of short and long annular Josephson tunnel junctions delimited by two confocal ellipses. The behavior of a circular annular Josephson tunnel junction is then seen to be simply a special case of the above result. For junctions having a normalized perimeter less than one, the threshold curves in the presence of an in-plane magnetic field of arbitrary orientations are derived and computed even in the case with trapped Josephson vortices. For longer junctions, a numerical analysis is carried out after the derivation of the appropriate motion equation for the Josephson phase. We found that the system is modeled by a modified and perturbed sine-Gordon equation with a space-dependent effective Josephson penetration length inversely proportional to the local junction width. Both the fluxon statics and dynamics are deeply affected by the non-uniform annulus width. Static zero-field multiple-fluxon solutions exist even in the presence of a large bias current. The tangential velocity of a traveling fluxon is not determined by the balance between the driving and drag forces due to the dissipative losses. Furthermore, the fluxon motion is characterized by a strong radial inward acceleration which causes electromagnetic radiation concentrated at the ellipse equatorial points.

  11. Potentiation of epithelial innate host responses by intercellular communication.

    Directory of Open Access Journals (Sweden)

    Tamas Dolowschiak

    Full Text Available The epithelium efficiently attracts immune cells upon infection despite the low number of pathogenic microbes and moderate levels of secreted chemokines per cell. Here we examined whether horizontal intercellular communication between cells may contribute to a coordinated response of the epithelium. Listeria monocytogenes infection, transfection, and microinjection of individual cells within a polarized intestinal epithelial cell layer were performed and activation was determined at the single cell level by fluorescence microscopy and flow cytometry. Surprisingly, chemokine production after L. monocytogenes infection was primarily observed in non-infected epithelial cells despite invasion-dependent cell activation. Whereas horizontal communication was independent of gap junction formation, cytokine secretion, ion fluxes, or nitric oxide synthesis, NADPH oxidase (Nox 4-dependent oxygen radical formation was required and sufficient to induce indirect epithelial cell activation. This is the first report to describe epithelial cell-cell communication in response to innate immune activation. Epithelial communication facilitates a coordinated infectious host defence at the very early stage of microbial infection.

  12. Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier.

    Science.gov (United States)

    Caron, Tyler J; Scott, Kathleen E; Fox, James G; Hagen, Susan J

    2015-10-28

    Long-term chronic infection with Helicobacter pylori (H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer, tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach, or dysfunction in the infected stomach, however, are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells, claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules, each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging, because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore, the role of H. pylori virulence factors, such as cytotoxin-associated gene A and vacoulating cytotoxin, in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo, likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study, as well, is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions, normally and in H. pylori infection, and make predictions about the consequences of claudin reorganization during H. pylori infection.

  13. Squamous Cell Carcinoma of Pancreas: Mystery and Facts.

    Science.gov (United States)

    Raghavapuram, Saikiran; Vaid, Arjun; Rego, Rayburn F

    2015-08-01

    Squamous cell carcinoma of the pancreas is very rare as pancreas does not have any squamous cells. Only a few cases have been reported in the literature so far. We describe such a case where in the patient presented with painless jaundice. CT and EUS confirmed the pancreatic mass biopsy of which showed squamous cell cancer.

  14. Basaloid squamous cell carcinoma involving floor of the mouth

    Directory of Open Access Journals (Sweden)

    Sah Kunal

    2008-01-01

    Full Text Available Basaloid squamous cell carcinomas of oral mucosa are uncommon. Majority of them can be differentiated from squamous cell carcinoma by their aggressive clinical course and their histopathological features. This case report presents a case of 70-year-old male with basaloid squamous cell carcinoma involving the floor of the mouth.

  15. Octagonal Defects at Carbon Nanotube Junctions

    Science.gov (United States)

    Jaskólski, W.; Pelc, M.; Chico, Leonor; Ayuela, A.

    2013-01-01

    We investigate knee-shaped junctions of semiconductor zigzag carbon nanotubes. Two dissimilar octagons appear at such junctions; one of them can reconstruct into a pair of pentagons. The junction with two octagons presents two degenerate localized states at Fermi energy (EF). The reconstructed junction has only one state near EF, indicating that these localized states are related to the octagonal defects. The inclusion of Coulomb interaction splits the localized states in the junction with two octagons, yielding an antiferromagnetic system. PMID:24089604

  16. Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium

    DEFF Research Database (Denmark)

    Smith, Ida Mosbech; Baker, A; Arneborg, Nils

    2015-01-01

    UNLABELLED: The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function....... In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability......). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. SIGNIFICANCE AND IMPACT...

  17. Gingival squamous cell carcinoma: A diagnostic impediment

    Science.gov (United States)

    Koduganti, Rekha Rani; Sehrawat, Sangeeta; Reddy, P. Veerendra Nath

    2012-01-01

    Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in women. More than 90% of oral cancer occurs in people older than 45 years Lesions of gingiva account for approximately 10% of the oral squamous cell carcinomas and may present clinically as an area of ulceration, exophytic mass, or red/white speckled patches. The proximity to the underlying periosteum may invite early bone invasion. Carcinoma of gingiva constitutes an extremely important group of neoplasms as the lesion frequently mimics the reactive and inflammatory conditions affecting the periodontium, delaying the diagnosis and making the prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma has been reported here, in a 40 Year old male patient. Careful recording of the case history and results of clinical examination, radiographic, and laboratory investigations, along with a critical review of similar conditions led to the diagnosis, and treatment was initiated. PMID:22628973

  18. [Vasculogenic mimicry in tongue squamous cell carcinoma].

    Science.gov (United States)

    Zhang, Xiaogen; Liu, Chundong; Luo, Luqiao; Cai, Xiaohui

    2013-04-01

    To investigate the presence of vasculogenic mimicry (VM) in tongue squamous cell carcinoma and explore its clinical significance. Forty-two surgical specimens of tongue squamous cell carcinoma were examined for the presence of VM using HE staining and double staining of CD34 and PAS. Of the 42 specimens, 18 (42.86%) showed the presence of VM. VM was not correlated with the patients' age or gender, but with lymph node metastasis and the grade of tumor differentiation. Compared with tumors without VM, the tumors with VM had a significantly higher rate of lymph node metastasis (P<0.05) and a lower grade of differentiation (P<0.05). VM can be present in tongue squamous cell carcinoma, and the poorly differentiated tumors contain more VM, which is associated with a greater likeliness of lymph node metastasis and a poorer prognosis.

  19. β-Conglycinin Reduces the Tight Junction Occludin and ZO-1 Expression in IPEC-J2

    Directory of Open Access Journals (Sweden)

    Yuan Zhao

    2014-01-01

    Full Text Available Soybean allergy presents a health threat to humans and animals. The mechanism by which food/feed allergen β-conglycinin injures the intestinal barrier has not been well understood. In this study, the changes of epithelial permeability, integrity, metabolic activity, the tight junction (TJ distribution and expression induced by β-conglycinin were evaluated using IPEC-J2 model. The results showed a significant decrease of trans-epithelial electrical resistance (TEER (p < 0.001 and metabolic activity (p < 0.001 and a remarkable increase of alkaline phosphatase (AP activity (p < 0.001 in a dose-dependent manner. The expression levels of tight junction occludin and ZO-1 were decreased (p < 0.05. The reduced fluorescence of targets and change of cellular morphology were recorded. The tight junction occludin and ZO-1 mRNA expression linearly declined with increasing β-conglycinin (p < 0.001.

  20. Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck

    Science.gov (United States)

    2017-01-24

    Head and Neck Cancer; Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

  1. Impact of laminitis on the canonical Wnt signaling pathway in basal epithelial cells of the equine digital laminae.

    Directory of Open Access Journals (Sweden)

    Le Wang

    Full Text Available The digital laminae is a two layer tissue that attaches the distal phalanx to the inner hoof wall, thus suspending the horse's axial skeleton in the hoof capsule. This tissue fails at the epidermal:dermal junction in laminitic horses, causing crippling disease. Basal epithelial cells line the laminar epidermal:dermal junction, undergo physiological change in laminitic horses, and lose versican gene expression. Versican gene expression is purportedly under control of the canonical Wnt signaling pathway and is a trigger for mesenchymal-to-epithelial transition; thus, its repression in laminar epithelial cells of laminitic horses may be associated with suppression of the canonical Wnt signaling pathway and loss of the epithelial cell phenotype. In support of the former contention, we show, using laminae from healthy horses and horses with carbohydrate overload-induced laminitis, quantitative real-time polymerase chain reaction, Western blotting after sodium dodecylsulfate polyacrylamide gel electrophoresis, and immunofluorescent tissue staining, that positive and negative regulatory components of the canonical Wnt signaling pathway are expressed in laminar basal epithelial cells of healthy horses. Furthermore, expression of positive regulators is suppressed and negative regulators elevated in laminae of laminitic compared to healthy horses. We also show that versican gene expression in the epithelial cells correlates positively with that of β-catenin and T-cell Factor 4, consistent with regulation by the canonical Wnt signaling pathway. In addition, gene and protein expression of β-catenin correlates positively with that of integrin β4 and both are strongly suppressed in laminar basal epithelial cells of laminitic horses, which remain E-cadherin(+/vimentin(-, excluding mesenchymal transition as contributing to loss of the adherens junction and hemidesmosome components. We propose that suppression of the canonical Wnt signaling pathway, and

  2. Squamous cell carcinoma with osteoclast-like giant cells masquerading as pleomorphic sarcoma: A rare case report

    Directory of Open Access Journals (Sweden)

    Khushboo Dewan

    2015-01-01

    Full Text Available Squamous cell carcinoma (SCC with osteoclast-like giant cells (OLGCs is a rare entity known to occur in skin, breast, lung, and pharynx. Only a single case of SCC containing OLGC in larynx has been reported so far. We report a case of a 65-year-old male patient presenting with sudden onset respiratory distress, who was subjected to biopsy, which was reported as undifferentiated sarcoma which was endorsed on laryngectomy specimen, however, sections from cervical lymph nodes revealed deposits of SCC. Extensive resectioning revealed a single focus showing origin of poorly differentiated carcinoma from the overlying squamous epithelium. Hence in undifferentiated pleomorphic sarcoma, a thorough sectioning and careful search for SCC including immunohistochemical markers should be done to exclude the possibility of a poorly differentiated epithelial malignancy.

  3. Enteropathogenic E. coli: breaking the intestinal tight junction barrier [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Anand Prakash Singh

    2016-05-01

    Full Text Available Enteropathogenic E. coli (EPEC causes acute intestinal infections in infants in the developing world. Infection typically spreads through contaminated food and water and leads to severe, watery diarrhea. EPEC attaches to the intestinal epithelial cells and directly injects virulence factors which modulate multiple signaling pathways leading to host cell dysfunction. However, the molecular mechanisms that regulate the onset of diarrhea are poorly defined. A major target of EPEC is the host cell tight junction complex which acts as a barrier and regulates the passage of water and solutes through the paracellular space. In this review, we focus on the EPEC effectors that target the epithelial barrier, alter its functions and contribute to leakage through the tight junctions.

  4. Modelling of Dual-Junction Solar Cells including Tunnel Junction

    Directory of Open Access Journals (Sweden)

    Abdelaziz Amine

    2013-01-01

    Full Text Available Monolithically stacked multijunction solar cells based on III–V semiconductors materials are the state-of-art of approach for high efficiency photovoltaic energy conversion, in particular for space applications. The individual subcells of the multi-junction structure are interconnected via tunnel diodes which must be optically transparent and connect the component cells with a minimum electrical resistance. The quality of these diodes determines the output performance of the solar cell. The purpose of this work is to contribute to the investigation of the tunnel electrical resistance of such a multi-junction cell through the analysis of the current-voltage (J-V characteristics under illumination. Our approach is based on an equivalent circuit model of a diode for each subcell. We examine the effect of tunnel resistance on the performance of a multi-junction cell using minimization of the least squares technique.

  5. Influence of Ionizing Radiation on Stromal-Epithelial Intercellular Communication in Esophageal Carcinogenesis

    Science.gov (United States)

    Patel, Zarana S.; Kalabis, Jiri; Rustgi, Anil K.; Cucinotta, Francis A.; Huff, Janice L.

    2010-01-01

    Esophageal cancer is the 6th leading cause of cancer death worldwide. Its development is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. An association with ionizing radiation exposure is revealed by the high excess relative risk for squamous cell carcinoma of the esophagus observed in the survivors of the atomic bomb detonations in Japan. It is also seen as a secondary malignancy in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely curable. The stromal microenvironment plays an essential role in the maintenance and modulation of normal epithelial cell growth and differentiation and cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibroblasts (Okawa et al., Genes & Dev. 2007. 21: 2788-2803). We examined how radiation treatment of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. Chemotactic and haptotactic migration of epithelial cells stimulated by conditioned media from irradiated fibroblasts was measured using assays conducted in Transwell cell culture chambers. Our results using

  6. PLEKHA7 is an adherens junction protein with a tissue distribution and subcellular localization distinct from ZO-1 and E-cadherin.

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    Pamela Pulimeno

    Full Text Available The pleckstrin-homology-domain-containing protein PLEKHA7 was recently identified as a protein linking the E-cadherin-p120 ctn complex to the microtubule cytoskeleton. Here we characterize the expression, tissue distribution and subcellular localization of PLEKHA7 by immunoblotting, immunofluorescence microscopy, immunoelectron microscopy, and northern blotting in mammalian tissues. Anti-PLEKHA7 antibodies label the junctional regions of cultured kidney epithelial cells by immunofluorescence microscopy, and major polypeptides of M(r approximately 135 kDa and approximately 145 kDa by immunoblotting of lysates of cells and tissues. Two PLEKHA7 transcripts ( approximately 5.5 kb and approximately 6.5 kb are detected in epithelial tissues. PLEKHA7 is detected at epithelial junctions in sections of kidney, liver, pancreas, intestine, retina, and cornea, and its tissue distribution and subcellular localization are distinct from ZO-1. For example, PLEKHA7 is not detected within kidney glomeruli. Similarly to E-cadherin, p120 ctn, beta-catenin and alpha-catenin, PLEKHA7 is concentrated in the apical junctional belt, but unlike these adherens junction markers, and similarly to afadin, PLEKHA7 is not localized along the lateral region of polarized epithelial cells. Immunoelectron microscopy definitively establishes that PLEKHA7 is localized at the adherens junctions in colonic epithelial cells, at a mean distance of 28 nm from the plasma membrane. In summary, we show that PLEKHA7 is a cytoplasmic component of the epithelial adherens junction belt, with a subcellular localization and tissue distribution that is distinct from that of ZO-1 and most AJ proteins, and we provide the first description of its distribution and localization in several tissues.

  7. Do cell junction protein mutations cause an airway phenotype in mice or humans?

    Science.gov (United States)

    Chang, Eugene H; Pezzulo, Alejandro A; Zabner, Joseph

    2011-08-01

    Cell junction proteins connect epithelial cells to each other and to the basement membrane. Genetic mutations of these proteins can cause alterations in some epithelia leading to varied phenotypes such as deafness, renal disease, skin disorders, and cancer. This review examines if genetic mutations in these proteins affect the function of lung airway epithelia. We review cell junction proteins with examples of disease mutation phenotypes in humans and in mouse knockout models. We also review which of these genes are expressed in airway epithelium by microarray expression profiling and immunocytochemistry. Last, we present a comprehensive literature review to find the lung phenotype when cell junction and adhesion genes are mutated or subject to targeted deletion. We found that in murine models, targeted deletion of cell junction and adhesion genes rarely result in a lung phenotype. Moreover, mutations in these genes in humans have no obvious lung phenotype. Our research suggests that simply because a cell junction or adhesion protein is expressed in an organ does not imply that it will exhibit a drastic phenotype when mutated. One explanation is that because a functioning lung is critical to survival, redundancy in the system is expected. Therefore mutations in a single gene might be compensated by a related function of a similar gene product. Further studies in human and animal models will help us understand the overlap in the function of cell junction gene products. Finally, it is possible that the human lung phenotype is subtle and has not yet been described.

  8. From motor-induced fluctuations to mesoscopic dynamics in epithelial tissues

    CERN Document Server

    Fodor, É; Comelles, J; Thiagarajan, R; Gov, N S; Visco, P; van Wijland, F; Riveline, D

    2015-01-01

    Molecular motors power spatial fluctuations in epithelial tissues. We evaluate these fluctuations in MDCK monolayers by tracking tricellular junctions, leading us to highlight the non-Gaussian statistics of the junction displacement. Using a mesoscopic framework which separates the thermal fluctuations orig- inating from the heat bath and the athermal ones generated by the motors, we quantify key parameters of the junction activity such as diffusion coefficient, persistence time and persistence length. When inhibiting specific targets in the molecular pathway which regulates the motors, we report subsequent modifications of these parameters: the hierarchy in the molecular pathway is correlated to the active fluctuations driving the junction dynamics. Our study provides a framework for quantifying nonequilibrium fluctuations in living matter with potential relevance for physiological shape transformations in the developing embryos.

  9. An immunohistochemical analysis of sex-steroid receptors, tumor suppressor gene p53 and Ki-67 in the normal and neoplastic uterine cervix squamous epithelium

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    Nikolaou Marinos

    2014-01-01

    Full Text Available Introduction. Malignant transformation of sex-steroid dependent tissues is associated with the loss of expression of sex steroid receptors as well as of the tumor suppression gene p53. The aim of this study is to evaluate the expression of sex-steroid receptors, p53 and Ki-67 in specimens from pre-malignant and malignant cervical epithelial lesions throughout the menstrual cycle. Material and Methods. Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous cervical epithelium, cervical intraepithelial neoplasia and invasive squamous cervical carcinoma, specimens utilizing antibodies against estrogen receptors, progesterone receptors, p53 protein and Ki-67 antigen. Results. In the samples taken from the normal cervical tissue, basal cells were usually estrogen receptor-positive, progesterone receptornegative, p53-negative and Ki-67-negative throughout the menstrual cycle. In contrast, para-basal cells were estrogen receptorpositive and progesterone receptor-negative in the follicular phase, but estrogen receptor-negative and progesterone receptor -positive and Ki-67 positive in the luteal phase. In cervical precancerous and cancer tissue samples (cervical intraepithelial neoplasia and squamous cervical carcinoma, the expression of estrogen receptors decreased. 31.15% of cervical intraepithelial neoplasia and 11.5% of squamous cervical carcinoma were positive for estrogen receptors. However, the expression of progesterone receptors increased. 29.5% of cervical intraepithelial neoplasia and 49.2% of squamous cervical carcinoma were positive for progesterone receptors. Positive staining for p53 was observed in 15 (24.59% cases of cervical intraepithelial neoplasia and in 39 (64% of squamous cervical carcinoma. The expression Ki-67 index in squamous cervical carcinoma cases (47.60% was significantly higher than of cervical intraepithelial neoplasia cases (30.2% (p=0.041. Conclusion. The

  10. Immunohistochemical profile of the penile urethra and differential expression of GATA3 in urothelial versus squamous cell carcinomas of the penile urethra.

    Science.gov (United States)

    Chaux, Alcides; Han, Jeong S; Lee, Stephen; Gonzalez-Roibon, Nilda; Sharma, Rajni; Burnett, Arthur L; Cubilla, Antonio L; Netto, George J

    2013-12-01

    The penile urethra has a distinctive morphology not yet fully characterized by immunohistochemistry. In addition, both urothelial and squamous cell carcinomas have been reported in the penile urethra, and the distinction between these 2 tumors might be difficult. The purposes of this study are to assess the histology and immunohistochemical profile (CK20, CK7, p63, and GATA3) of the penile urethra and to assess the usefulness of Trans-acting T-cell-specific transcription factor (GATA3) and human papillomavirus detection in distinguishing urothelial versus squamous cell carcinomas. Normal penile urethra was evaluated in 11 total penectomies. The penile urethra was lined by 2 cell layers: a superficial single layer of CK7+, CK20-, and p63- columnar cells and a deep stratified layer of CK7-, CK20-, and p63+ cubical cells. Both layers were GATA3+, supporting urothelial differentiation. In addition, 2 tissue microarrays and 6 surgical specimens of primary tumors of the penile urethra (3 urothelial and 3 squamous cell carcinomas) were evaluated for GATA3 expression. In the tissue microarrays, 22 of 25 upper tract urothelial carcinomas and 0 of 38 penile squamous cell carcinomas were GATA3+. In the surgical specimens, GATA3 was positive in all urothelial carcinomas and negative in all squamous cell carcinomas. Human papillomavirus was detected in 2 of 3 squamous cell carcinomas and in 0 of 3 of the urothelial carcinomas. In conclusion, the penile urethra is covered by epithelial cells that are unique in morphology and immunohistochemical profile. In addition, our study suggests that GATA3 and human papillomavirus detection are useful markers for distinguishing urothelial carcinomas from squamous cell carcinomas of the penile urethra.

  11. with esophageal squamous cell cancer

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    Tao Li

    2017-02-01

    Full Text Available Purpose: The aim of this study was to retrospectively observe and analyze the long-term treatment outcomes of 191 elderly patients with esophageal squamous cell cancer (ESCC who were treated with californium-252 (252Cf neutron brachytherapy (NBT in combination with external beam radiotherapy (EBRT. Material and methods : From January 2002 to November 2012, 191 patients with ESCC underwent NBT in combination with EBRT. The total radiation dose to the reference point via NBT was 8-25 Gy-eq in two to five fractions with one fraction per week. The total dose via EBRT was 50-60 Gy, which was delivered over a period of 5 to 6 weeks with normal fractionation. Results : The median survival time for the 191 patients was 23.6 months, and the 5-year rates for overall survival (OS and local-regional control (LRC were 28.7% and 54.2%, respectively. The patients’ age was a factor that was significantly associated with OS (p = 0.010, according to univariate analysis. The 5-year OS (LRC was 37.3% (58.6% for patients aged 70-74 years and 14.5% (47.9% for patients aged > 74 years (p = 0.010 and p = 0.038. In multivariate analysis, age and clinical N stage were associated with OS and LRC (p = 0.011 [0.041] and p = 0.005 [0.005]. From the time of treatment completion to the development of local-regional recurrence or death, 5 (2.6% patients experienced fistula and 15 (7.9% experienced massive bleeding. The incidence of severe late complications was related to older age (p = 0.027, higher NBT dose/fraction (20-25 Gy/5 fractions, and higher total dose (> 66 Gy. Conclusions : The clinical data indicated that NBT in combination with EBRT produced favorable local control and long-term survival rates for elderly patients with ESCC, and that the side effects were tolerable. Patient’s age, clinical stage N status, and radiation dose could be used to select the appropriate treatment for elderly patients.

  12. The value of the Lugol's iodine staining technique for the identification of vaginal epithelial cells.

    Science.gov (United States)

    Hausmann, R; Pregler, C; Schellmann, B

    1994-01-01

    This paper reports on the specificity of the Lugol's iodine staining technique for the detection of vaginal epithelial cells on penile swabs. Air-dried swabs taken from the glans of the penis of 153 hospital patients and from 50 healthy volunteers, whose last sexual intercourse had taken place at least 5 days previously, were stained with Lugol's solution. Glycogenated cells were found in more than 50% of the cases studied, even in healthy volunteers without urethritis. In almost all of these cases the smear contained at least a few polygonal nucleated epithelial cells showing an unequivocal positive Lugol reaction. These cells cannot be distinguished from superficial or intermediate vaginal cells, by cytomorphology or staining. Urinary tract infections had no influence on the glycogen content of male squamous epithelial cells. On the basis of these results the Lugol's method can no longer be assumed to prove the presence of vaginal cells in penile swabs.

  13. Focal epithelial hyperplasia arising after delivery of metal-ceramic fixed dental prosthesis.

    Science.gov (United States)

    Park, Min-Woo; Cho, Young-Ah; Kim, Soung-Min; Myoung, Hoon; Lee, Jong-Ho; Lee, Suk-Keun

    2014-12-01

    Focal epithelial hyperplasia (FEH) is a human papillomavirus (HPV)-induced alteration of the oral mucosa that presents with a clinically distinct appearance. While other HPV-infected lesions such as squamous papilloma, verruca vulgaris, and condyloma acuminatum involve the skin, oral mucosa, and genital mucosa, FEH occurs only in the oral mucosa. The affected oral mucosa exhibits multiple papules and nodules with each papule/nodule being flat-topped or sessile. The affected region resembles the normal color of oral mucosa rather than appearing as a white color since the epithelial surface is not hyperkeratinized. Almost all cases present with multiple sites of occurrence. This rare, benign epithelial proliferation is related to low-risk HPV, especially HPV-13 and -32, and is not transformed into carcinoma. We report a case of FEH that arose on the attached gingiva of an East Asian male adult related to prosthesis without detection of any HPV subtype in HPV DNA chip and sequencing.

  14. Coronaviruses in polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Bekker, C P; Voorhout, W F; Horzinek, M C; Van der Ende, A; Strous, G J; Rottier, P J

    1995-01-01

    Coronaviruses have a marked tropism for epithelial cells. In this paper the interactions of the porcine transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV-A59) with epithelial cells are compared. Porcine (LLC-PK1) and murine (mTAL) epithelial cells were grown on permeable supp

  15. Normal morphogenesis of epithelial tissues and progression of epithelial tumors.

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A

    2012-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted.

  16. Incidence of epithelial lesions of the conjunctiva in a review of 12,102 specimens in Canada (Quebec

    Directory of Open Access Journals (Sweden)

    Luiz Filipe de Albuquerque Alves

    2011-02-01

    Full Text Available PURPOSE: The purpose of this study was to assess the relative frequency of epithelial lesions of the conjunctiva in Canada. METHODS: A retrospective study of 12,102 consecutive cases received during 16 years (1993-2009 at the Henry C. Witelson Ocular Pathology Laboratory in Montreal, Canada, was performed. Demographic data was retrieved from histopathological request forms and specimens were categorized and analyzed by mean percentage. The relative frequency of epithelial lesions of the conjunctiva from a single center in Canada, representing the province of Quebec was reviewed. RESULTS: Of the 12,102 specimens reviewed, 273 were conjunctival lesions (2.25%, including 86 epithelial tumors (0.71% of the conjunctiva that comprised the studied sample. The average age of these patients was 59.9 ± 17.6 years, and gender distribution was 66 (69% males and 30 (31% females. Fifteen lesions (17.4% were classified as squamous cell papillomas (mean age, 57.3 ± 16.7 years. Within the ocular surface squamous neoplasia (OSSN spectrum, there were 10 (11.6% actinic keratosis (63.8 ± 17.6 years, 27 (31.3% cases of conjunctival intraepithelial neoplasia (CIN with variable degrees of atypia (mild to moderate (63.9 ± 15.3 years, 15 (17.4% carcinomas in situ (66.7 ± 18.0 years, and 17 (19.7% squamous cell carcinomas (SCC (56.2 ± 19.4 years. Two other rare cases of malignant tumors included one basal cell carcinoma and one mucoepidermoid carcinoma. CONCLUSIONS: The distribution of our sample is similar to the one reported by the American Forces Institute of Pathology (AFIP in 1994. When we compare our sample to others coming from countries with high levels of sunlight exposure, we found a lower incidence of ocular surface squamous neoplasia, including squamous cell carcinomas in Canada.

  17. Review of squamous premalignant vulvar lesions.

    NARCIS (Netherlands)

    Nieuwenhof, H.P. van de; Avoort, I.A.M. van der; Hullu, J.A. de

    2008-01-01

    Vulvar squamous cell carcinoma (SCC) develops following two different pathways, which have their own premalignant lesions. In the absence of human papilloma virus (HPV), vulvar SCC can develop in a background of lichen sclerosus (LS), differentiated vulvar intraepithelial neoplasia (VIN) or both. Th

  18. Verrucous Squamous Cell Cancer in the Esophagus

    DEFF Research Database (Denmark)

    Egeland, C; Achiam, M P; Federspiel, B

    2016-01-01

    Verrucous carcinoma is a rare, slow-growing type of squamous cell cancer. Fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide. In 2014, two male patients were diagnosed with verrucous carcinoma in the distal part of the esophagus. The endoscopic...

  19. Management of anal squamous intraepithelial lesions.

    Science.gov (United States)

    Pineda, Carlos E; Welton, Mark L

    2009-05-01

    Anal squamous intraepithelial lesions include both low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and are caused by chronic infection with the human papillomavirus (HPV). The disease is increasing in both incidence and prevalence, especially among patients with the following risk factors: homosexual men, acquired or iatrogenic immunosuppression, and presence of other HPV-related diseases. Although the natural history of the disease is unknown, there is significant evidence that untreated HSIL progresses to squamous cell carcinoma in 11% of patients and in up to 50% of patients with extensive disease and immunosuppression. Anal cytology and reflex HPV DNA testing are used to screen for disease, particularly among patients with the aforementioned risk factors. Evaluation of the patient should include physical examination and high-resolution anoscopy (HRA) to evaluate for disease above and below the dentate line. Intervention is warranted and this can be achieved in many ways. The treatment option associated with the best outcomes is ablation directed with HRA, which can be performed in the office or in the operating room with minimal morbidity. This strategy is effective in patients with both low-volume and high-volume disease and is associated with a malignant progression rate of 0.4% in patients with treated HSIL.

  20. Review of squamous premalignant vulvar lesions.

    NARCIS (Netherlands)

    Nieuwenhof, H.P. van de; Avoort, I.A.M. van der; Hullu, J.A. de

    2008-01-01

    Vulvar squamous cell carcinoma (SCC) develops following two different pathways, which have their own premalignant lesions. In the absence of human papilloma virus (HPV), vulvar SCC can develop in a background of lichen sclerosus (LS), differentiated vulvar intraepithelial neoplasia (VIN) or both. Th

  1. Continual exposure to cigarette smoke extracts induces tumor-like transformation of human nontumor bronchial epithelial cells in a microfluidic chip.

    Science.gov (United States)

    Li, Encheng; Xu, Zhiyun; Liu, Fen; Wang, Huiling; Wen, Jiabin; Shao, Shujuan; Zhang, Lichuan; Wang, Lei; Liu, Chong; Lu, Jianxin; Wang, Wenxin; Gao, Zhancheng; Wang, Qi

    2014-08-01

    Heavy cigarette smoking-related chronic obstructive pulmonary disease is an independent risk factor for lung squamous carcinoma. However, the mechanisms underlying the malignant transformation of bronchial epithelial cells are unclear. In our study, human tumor-adjacent bronchial epithelial cells were obtained from 10 cases with smoking-related chronic obstructive pulmonary disease and lung squamous carcinoma and cultured in an established microfluidic chip for continual exposure to cigarette smoke extracts (CSE) to investigate the potential tumor-like transformation and mechanisms. The integrated microfluidic chip included upstream concentration gradient generator and downstream cell culture chambers supplied by flowing medium containing different concentrations of CSE. Our results showed that continual exposure to low doses of CSE promoted cell proliferation whereas to high doses of CSE triggered cell apoptosis. Continual exposure to CSE promoted reactive oxygen species production in human epithelial cells in a dose-dependent manner. More importantly, continual exposure to low dose of CSE promoted the epithelial-to-mesenchymal transition process and anchorage-independent growth, and increased chromosome instability in bronchial epithelial cells, accompanied by activating the GRP78, NF-κB, and PI3K pathways. The established microfluidic chip is suitable for primary culture of human tumor-adjacent bronchial epithelial cells to investigate the malignant transformation. Continual exposure to low doses of CSE promoted tumor-like transformation of human nontumor bronchial epithelial cells by inducing reactive oxygen species production and activating the relevant signaling.

  2. Basolateral junction proteins regulate competition for the follicle stem cell niche in the Drosophila ovary.

    Science.gov (United States)

    Kronen, Maria R; Schoenfelder, Kevin P; Klein, Allon M; Nystul, Todd G

    2014-01-01

    Epithelial stem cells are routinely lost or damaged during adult life and must therefore be replaced to maintain homeostasis. Recent studies indicate that stem cell replacement occurs through neutral competition in many types of epithelial tissues, but little is known about the factors that determine competitive outcome. The epithelial follicle stem cells (FSCs) in the Drosophila ovary are regularly lost and replaced during normal homeostasis, and we show that FSC replacement conforms to a model of neutral competition. In addition, we found that FSCs mutant for the basolateral junction genes, lethal giant larvae (lgl) or discs large (dlg), undergo a biased competition for niche occupancy characterized by increased invasion of neighboring FSCs and reduced loss. Interestingly, FSCs mutant for a third basolateral junction gene, scribble (scrib), do not exhibit biased competition, suggesting that Lgl and Dlg regulate niche competition through a Scrib-independent process. Lastly, we found that FSCs have a unique cell polarity characterized by broadly distributed adherens junctions and the lack of a mature apical domain. Collectively, these observations indicate that Lgl and Dlg promote the differentiation of FSC progeny to a state in which they are less prone to invade the neighboring niche. In addition, we demonstrate that the neutral drift model can be adapted to quantify non-neutral behavior of mutant clones.

  3. Basolateral junction proteins regulate competition for the follicle stem cell niche in the Drosophila ovary.

    Directory of Open Access Journals (Sweden)

    Maria R Kronen

    Full Text Available Epithelial stem cells are routinely lost or damaged during adult life and must therefore be replaced to maintain homeostasis. Recent studies indicate that stem cell replacement occurs through neutral competition in many types of epithelial tissues, but little is known about the factors that determine competitive outcome. The epithelial follicle stem cells (FSCs in the Drosophila ovary are regularly lost and replaced during normal homeostasis, and we show that FSC replacement conforms to a model of neutral competition. In addition, we found that FSCs mutant for the basolateral junction genes, lethal giant larvae (lgl or discs large (dlg, undergo a biased competition for niche occupancy characterized by increased invasion of neighboring FSCs and reduced loss. Interestingly, FSCs mutant for a third basolateral junction gene, scribble (scrib, do not exhibit biased competition, suggesting that Lgl and Dlg regulate niche competition through a Scrib-independent process. Lastly, we found that FSCs have a unique cell polarity characterized by broadly distributed adherens junctions and the lack of a mature apical domain. Collectively, these observations indicate that Lgl and Dlg promote the differentiation of FSC progeny to a state in which they are less prone to invade the neighboring niche. In addition, we demonstrate that the neutral drift model can be adapted to quantify non-neutral behavior of mutant clones.

  4. Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon.

    Directory of Open Access Journals (Sweden)

    Yosuke Shimada

    Full Text Available Microbiota have been shown to have a great influence on functions of intestinal epithelial cells (ECs. The role of indole as a quorum-sensing (QS molecule mediating intercellular signals in bacteria has been well appreciated. However, it remains unknown whether indole has beneficial effects on maintaining intestinal barriers in vivo. In this study, we analyzed the effect of indole on ECs using a germ free (GF mouse model. GF mice showed decreased expression of junctional complex molecules in colonic ECs. The feces of specific pathogen-free (SPF mice contained a high amount of indole; however the amount was significantly decreased in the feces of GF mice by 27-fold. Oral administration of indole-containing capsules resulted in increased expression of both tight junction (TJ- and adherens junction (AJ-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate (DSS-induced colitis. A similar protective effect of indole on DSS-induced epithelial damage was also observed in mice bred in SPF conditions. These findings highlight the beneficial role of indole in establishing an epithelial barrier in vivo.

  5. Gap junctions - guards of excitability.

    Science.gov (United States)

    Stroemlund, Line Waring; Jensen, Christa Funch; Qvortrup, Klaus; Delmar, Mario; Nielsen, Morten Schak

    2015-06-01

    Cardiomyocytes are connected by mechanical and electrical junctions located at the intercalated discs (IDs). Although these structures have long been known, it is becoming increasingly clear that their components interact. This review describes the involvement of the ID in electrical disturbances of the heart and focuses on the role of the gap junctional protein connexin 43 (Cx43). Current evidence shows that Cx43 plays a crucial role in organizing microtubules at the intercalated disc and thereby regulating the trafficking of the cardiac sodium channel NaV1.5 to the membrane.

  6. The adherens junctions control susceptibility to Staphylococcus aureus α-toxin.

    Science.gov (United States)

    Popov, Lauren M; Marceau, Caleb D; Starkl, Philipp M; Lumb, Jennifer H; Shah, Jimit; Guerrera, Diego; Cooper, Rachel L; Merakou, Christina; Bouley, Donna M; Meng, Wenxiang; Kiyonari, Hiroshi; Takeichi, Masatoshi; Galli, Stephen J; Bagnoli, Fabio; Citi, Sandra; Carette, Jan E; Amieva, Manuel R

    2015-11-17

    Staphylococcus aureus is both a transient skin colonizer and a formidable human pathogen, ranking among the leading causes of skin and soft tissue infections as well as severe pneumonia. The secreted bacterial α-toxin is essential for S. aureus virulence in these epithelial diseases. To discover host cellular factors required for α-toxin cytotoxicity, we conducted a genetic screen using mutagenized haploid human cells. Our screen identified a cytoplasmic member of the adherens junctions, plekstrin-homology domain containing protein 7 (PLEKHA7), as the second most significantly enriched gene after the known α-toxin receptor, a disintegrin and metalloprotease 10 (ADAM10). Here we report a new, unexpected role for PLEKHA7 and several components of cellular adherens junctions in controlling susceptibility to S. aureus α-toxin. We find that despite being injured by α-toxin pore formation, PLEKHA7 knockout cells recover after intoxication. By infecting PLEKHA7(-/-) mice with methicillin-resistant S. aureus USA300 LAC strain, we demonstrate that this junctional protein controls disease severity in both skin infection and lethal S. aureus pneumonia. Our results suggest that adherens junctions actively control cellular responses to a potent pore-forming bacterial toxin and identify PLEKHA7 as a potential nonessential host target to reduce S. aureus virulence during epithelial infections.

  7. West Nile virus infection causes endocytosis of a specific subset of tight junction membrane proteins.

    Directory of Open Access Journals (Sweden)

    Zaikun Xu

    Full Text Available West Nile virus (WNV is a blood-borne pathogen that causes systemic infections and serious neurological disease in human and animals. The most common route of infection is mosquito bites and therefore, the virus must cross a number of polarized cell layers to gain access to organ tissue and the central nervous system. Resistance to trans-cellular movement of macromolecules between epithelial and endothelial cells is mediated by tight junction complexes. While a number of recent studies have documented that WNV infection negatively impacts the barrier function of tight junctions, the intracellular mechanism by which this occurs is poorly understood. In the present study, we report that endocytosis of a subset of tight junction membrane proteins including claudin-1 and JAM-1 occurs in WNV infected epithelial and endothelial cells. This process, which ultimately results in lysosomal degradation of the proteins, is dependent on the GTPase dynamin and microtubule-based transport. Finally, infection of polarized cells with the related flavivirus, Dengue virus-2, did not result in significant loss of tight junction membrane proteins. These results suggest that neurotropic flaviviruses such as WNV modulate the host cell environment differently than hemorrhagic flaviviruses and thus may have implications for understanding the molecular basis for neuroinvasion.

  8. Squamous cell carcinoma in Kauai, Hawaii.

    Science.gov (United States)

    Chuang, T Y; Reizner, G T; Elpern, D J; Stone, J L; Farmer, E R

    1995-06-01

    It is estimated that over 100,000 new cases of squamous cell carcinoma are diagnosed in the United States annually. This number is compounded by an increasing concern over the ozone layer depletion and the continued sunbathing behavior of many individuals. This could be particularly acute in Hawaii, which may have the highest rates of skin cancer in the country. We believe the updated information on skin cancer is essential to address the magnitude of the problem. A prospective 5-year population-based incidence study was conducted on Kauai, Hawaii, between 1983 and 1987 to investigate the frequency of squamous cell carcinomas in resident Caucasians. A total of 58 residents, 37 men and 21 women, were identified with an initial episode of squamous cell carcinoma during the 5-year period. The average annual incidence rate per 100,000 Kauai Caucasian residents, standardized to the 1980 U.S. white population, was 153 for men and 92 for women with a combined rate of 118. The average patient age was 66.4 years. The head and neck was the most common anatomic site, with the extremities second. Subsequent new squamous cell carcinoma occurred in 13.8% of patients. Only one patient (2%) developed a recurrence after treatment. Twenty-five patients (43%) had basal cell carcinoma simultaneously or at other earlier times. In Kauai the incidence rate of squamous cell carcinoma is the highest yet documented in the United States. No consistent trend in incidence rates was appreciated during this 5-year period.

  9. Cell proliferation of esophageal squamous epithelium in erosive and non-erosive reflux disease

    Institute of Scientific and Technical Information of China (English)

    Carlo Calabrese; Davide Trerè; Lorenzo Montanaro; Giuseppina Liguori; Elisa Brighenti; Mauela Vici; Paolo Gionchetti; Fernando Rizzello; Massimo Campieri; Massimo Derenzini

    2011-01-01

    AIM: To elucidate cell proliferation in erosive reflux disease (ERD) and non-erosive reflux disease (NERD), we evaluated markers in squamous epithelial cells. METHODS: Thirty-four consecutive patients with gastroesophageal- reflux-disease-related symptoms (21 NERD and 13 ERD) were evaluated for the enrolment into the study. All patients underwent 24-h pH monitoring, standard endoscopy, and biopsy for histological evaluation. The expression of cyclins D and A was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) from isolated epithelial cells. In all samples, analysis of the isolated cell population revealed the presence of epithelial cells only. RESULTS: Real-time RT-PCR showed that, in patients with ERD, the relative expression of cyclin D1 mRNA in esophageal epithelium was strongly decreased in comparison with NERD patients. The mean value of relative expression of cyclin D1 mRNA in NERD patients was 3.44 ± 1.9, whereas in ERD patients, it was 1.32 ± 0.87 (P = 0.011). Real-time RT-PCR showed that, in patients with ERD, relative expression of cyclin A mRNA in esophageal epithelium was decreased in comparison with that in NERD patients (2.31 ± 2.87 vs 0.66 ± 1.11). The mean bromodeoxyuridine labeling index in the NERD patients was 5.42% ± 1.68%, whereas in ERD patients, it was 4.3% ± 1.59%. CONCLUSION: We confirmed reduced epithelial proliferation in ERD compared with NERD patients, and that individuals who develop ERD are characterized by weaker epithelial cell proliferation.

  10. Bone marrow-derived cells contribute to NDEA-induced lung squamous cell carcinoma.

    Science.gov (United States)

    Luo, Dan; Liu, Dengqun; Zhou, Xiangdong; Yang, Shiming; Tang, Chunlan; Liu, Guoxiang

    2013-02-01

    Bone marrow-derived stem cells (BMDCs) have the ability to differentiate into lung epithelial cells in response to damage; however, their role in squamous cell carcinoma (SCC) formation is unknown. This study aimed to determine whether BMDC-derived lung epithelial cells could contribute to SCC formation. A model of lung SCC induced with N-nitrosodiethylamine (NDEA) in recipient female mice transplanted with green fluorescent protein (GFP)-positive BMDCs from male donors was established. Incorporation of BMDCs in lung tissue was determined using immunohistochemistry and immunofluorescence to detect GFP expression and fluorescence in situ hybridization to Y chromosomes. BMDC appeared at three stages of lung SCC progression: metaplasia, dysplasia, and carcinoma. There was a significantly higher proportion of GFP-positive (GFP(+)) cells within SCC than was found in metaplasia and dysplasia 16 weeks post-transplantation (both P cells in SCC were pancytokeratin-positive (PCK(+)) epithelial cells, and some exhibited proliferative activity as determined by Ki67 staining (9.7 ± 3.92 %). The presence of GFP(+)Ki67(+)PCK(+) cells within SCC nests suggested that some donor BMDCs differentiated into proliferating epithelial cells. Finally, analysis of p63 expression, a marker of SCC cells, indicated that the presence of GFP(+)p63(+) cells (green) in inner parts of the SCC. These findings strongly suggest that BMDC-derived lung epithelial cells could participate in lung SCC formation and partially contribute to tumor growth, which might have significant potential implications for both clinical cancer therapy using BMDCs.

  11. Vaginal epithelial dendritic cells renew from bone marrow precursors.

    Science.gov (United States)

    Iijima, Norifumi; Linehan, Melissa M; Saeland, Sem; Iwasaki, Akiko

    2007-11-27

    Dendritic cells (DCs) represent key professional antigen-presenting cells capable of initiating primary immune responses. A specialized subset of DCs, the Langerhans cells (LCs), are located in the stratified squamous epithelial layer of the skin and within the mucosal epithelial lining of the vaginal and oral cavities. The vaginal mucosa undergoes cyclic changes under the control of sex hormones, and the renewal characteristics of the vaginal epithelial DCs (VEDCs) remain unknown. Here, we examined the origin of VEDCs. In contrast to the skin epidermal LCs, the DCs in the epithelium of the vagina were found to be repopulated mainly by nonmonocyte bone-marrow-derived precursors, with a half-life of 13 days under steady-state conditions. Upon infection with HSV-2, the Gr-1(hi) monocytes were found to give rise to VEDCs. Furthermore, flow cytometric analysis of the VEDCs revealed the presence of at least three distinct populations, namely, CD11b(+)F4/80(hi), CD11b(+)F4/80(int), and CD11b(-)F4/80(-). Importantly, these VEDC populations expressed CD207 at low levels and had a constitutively more activated phenotype compared with the skin LCs. Collectively, our results revealed mucosa-specific features of the VEDCs with respect to their phenotype, activation status, and homeostatic renewal potential.

  12. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens

    Science.gov (United States)

    Awad, Wageha A.; Hess, Claudia; Hess, Michael

    2017-01-01

    Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens

  13. Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens

    Directory of Open Access Journals (Sweden)

    Wageha A. Awad

    2017-02-01

    Full Text Available Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis

  14. Effect of heat stress on intestinal barrier function of human intestinal epithelial Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Gui-zhen XIAO

    2013-07-01

    Full Text Available Objective To investigate the heat stress-induced dysfunction of intestinal barrier including intestinal tight junction and apoptosis of epithelial cells. Methods Human intestinal epithelial Caco-2 cell monolayers, serving as the intestinal barrier model, were exposed to different temperature (37-43℃ for designated time. Transepithelial electrical resistance (TEER and horseradish peroxidase (HRP flux permeability were measured to evaluate barrier integrity. Level of tight junction (TJ protein occludin was analyzed by Western blotting. Cell apoptosis rate was determined using Annexin V-FITC/PI kit by flow cytometry. Results Compared with the 37℃ group, TEER lowered and the permeability for HRP increased significantly after heat exposure (P<0.01 in 39℃, 41℃ and 43℃ groups. The expression of occludin increased when the temperature was elevated from 37℃ to 41℃, and it reached the maximal level at 41℃. However, its expression gradually decreased with passage of time at 43℃. Cell apoptosis was enhanced with elevation of the temperature (P<0.05 or P<0.01. Conclusion Heat stress can induce damage to tight junction and enhance apoptosis of epithelial cells, thus causing dysfunction of intestinal epithelial barrier.

  15. Spectrum of Lesions Affecting the Renal Pelvis and Pelviureteric Junction: A 13-Year Retrospective Analysis

    Science.gov (United States)

    Kini, Hema; Suresh, Pooja Kundapur; Guni, Laxman Prabhu Gurupur; Bhat, Shaila; Kini, Jyoti Ramanath

    2016-01-01

    Introduction Both, the renal pelvis and the ureter, are affected by developmental, reactive and neoplastic disorders, though rare in incidence. Aim This series of cases were analysed to study the clinicopathological characteristics of the common and comparatively rare lesions involving the renal pelvis and pelviureteric junction. Materials and Methods A retrospective collection of 476 nephrectomies and pelviureteric junction resections, received over a period of 13 years from 2001 to 2013 was done. The patients’ clinical details were obtained and the histopathological findings reviewed. The lesions were classified into non-neoplastic and neoplastic categories. Results Primary involvement of the renal pelvis and pelviureteric junction was seen in 105 of 476 specimens. The mean age was 54.5 years with a male to female ratio of 2.2:1. The non-neoplastic lesions accounted for 76.2% of cases with a majority being pelviureteric junction obstruction due to inflammation induced fibromuscular hypertrophy (68.6%) causing hydronephrosis. Urothelial carcinomas were encountered in 20% of the cases. A majority of the urothelial carcinomas were infiltrative (81%) and high grade (71%) tumours. Conclusion Renal pelvis, a conduit to propel urine, can be the site for numerous disorders. Non-neoplastic lesions were more common than neoplasms. Pelviureteric junction obstruction due to inflammation induced fibromuscular hypertrophy was the commonest lesion in our study. In the neoplastic category, urothelial carcinoma was most common. However, rare lesions such as hamartomatous fibroepithelial polyp, Von Brunn’s nests, flat urothelial hyperplasia and intramuscular haemangioma of upper ureter at the pelviureteric junction were encountered along with occasional cases of tuberculosis and squamous cell carcinomas. PMID:27042468

  16. Basement membrane proteoglycans are of epithelial origin in rodent skin

    DEFF Research Database (Denmark)

    Yamane, Y; Yaoita, H; Couchman, J R

    1996-01-01

    proteoglycan and rat and mouse perlecan. While the isolated rat epidermis was shown to completely lack rat basement membrane chondroitin sulfate proteoglycan and rat basement membrane heparan sulfate proteoglycans, including perlecan, immunofluorescence staining of tissue sections from the grafted sites......-epidermal junction and hair follicle epithelium are of epidermal (epithelial) origin in vivo. Stratified rat keratinocytes cultured on a collagen matrix at the air-liquid interface showed the synthesis of perlecan, laminin 1, and type IV collagen in basement membranes, but not clearly detectable basement membrane...

  17. Role of Allergen Source-Derived Proteases in Sensitization via Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Yasuhiro Matsumura

    2012-01-01

    Full Text Available Protease activity is a characteristic common to many allergens. Allergen source-derived proteases interact with lung epithelial cells, which are now thought to play vital roles in both innate and adaptive immune responses. Allergen source-derived proteases act on airway epithelial cells to induce disruption of the tight junctions between epithelial cells, activation of protease-activated receptor-2, and the production of thymic stromal lymphopoietin. These facilitate allergen delivery across epithelial layers and enhance allergenicity or directly activate the immune system through a nonallergic mechanism. Furthermore, they cleave regulatory cell surface molecules involved in allergic reactions. Thus, allergen source-derived proteases are a potentially critical factor in the development of allergic sensitization and appear to be strongly associated with heightened allergenicity.

  18. Control over Rectification in Supramolecular Tunneling Junctions

    NARCIS (Netherlands)

    Wimbush, K.S.; Wimbush, Kim S.; Reus, William F.; van der Wiel, Wilfred Gerard; Reinhoudt, David; Whitesides, George M.; Nijhuis, C.A.; Velders, Aldrik

    2010-01-01

    In complete control: The magnitude of current rectification in well-defined supramolecular tunneling junctions can be controlled by changing the terminal functionality (red spheres) of dendrimers (gray spheres) immobilized on a supramolecular platform (see picture). Junctions containing biferrocene

  19. E-cadherin and c-Met expression in actinic cheilits and lip squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    A Martínez

    2011-12-01

    Full Text Available Objective: The aim of this study was to assess epithelial expression of E-cadherin and c-Met in normal lip, in actinic cheilitis and lip squamous cell carcinoma. Study Design: Biopsies of normal lip vermillion (NL, n=18, actinic cheilitis (AC, n=37, and lip SCC (n=22 were processed for E-cadherin and c-Met immunodetection. Epithelial and tumor cell expression was scored for each sample considering staining intensity and percentage. Results: E-cadherin expression was significantly reduced in AC and lip SCC as compared to normal lip (P<0.05, with a significant reduction in lip SCC as compared to AC (P=0.003. Expression of c-Met was significantly higher in AC and lip SCC as compared to NL (P<0.05, with a significant increase in lip SCC as compared to AC (P<0.0001. Conclusion: The results showed that epithelial E-cadherin expression is reduced and c-Met expression is increased as lip carcinogenesis progresses, suggesting that these proteins may be useful markers of malignant transformation.

  20. Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    YANG Yan-li; XU Kan-lun; ZHOU Yan; GAO Xin; CHEN Li-rong

    2012-01-01

    Background Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane.The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC,and help to identify patients who may benefit from EGFR targeted therapies.Methods Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC,16 cases of squamous epithelial atypical hyperplasia,and 11 cases of normal esophageal tissue.Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC,eight cases of squamous epithelial atypical hyperplasia,and eight samples of normal esophageal tissue.Results The IHC-positive rates of EGFR in 105 cases of ESCC,16 cases of squamous epithelial atypical hyperplasia,and 11 normal esophageal tissues were 97% (102/105),44% (7/16),and 18% (2/11) respectively.The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P <0.05).Among the 105 cases of ESCC,overexpression of EGFR was found in 90 cases (86%),of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+.In ESCC,the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P<0.05),but not with other parameters.The FISH-positive rates of EGFR in 80 cases of ESCC,the eight cases of squamous epithelial atypical hyperplasia,and eight samples of normal esophageal tissue were 31.3% (25/80),0 (0/8) and 0 (0/8) respectively.In ESCC,EGFR gene amplification was found in 17 (21%) cases,high polysomy in 8 (10%) cases,disomy in 34 cases,low trisomy in 17 cases,and high trisomy in four cases.EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P <0.05).EGFR FISH-positive was significantly associated with overexpression of EGFR.Conclusion Protein

  1. Nano-Molecular Junctions on STM Tips

    Institute of Scientific and Technical Information of China (English)

    Chun Huang∗; Jianshu Yang

    2011-01-01

    We present a technique for building metal-organic-metal junctions, which contain ten or fewer conjugated molecules between each of such junction, and the investigations of the I-V response of these junctions. The junctions are made by self assembling thiolated molecules onto gold coated tips for use in scanning tunneling microscopy. We show that this easy technique probes the qualitative properties of the molecules. Current-voltage characteristics of a Tour wire and a new molecular rectifier are presented.

  2. Nano-Molecular Junctions on STM Tips

    Institute of Scientific and Technical Information of China (English)

    Chun Huang; Jianshu Yang

    2011-01-01

    We present a technique for building metal-organic-metal junctions, which contain ten or fewer conjugated molecules between each of such junction, and the investigations of the I-V response of these junctions.The junctions are made by self assembling thiolated molecules onto gold coated tips for use in scanning tunneling microscopy. We show that this easy technique probes the qualitative properties of the molecules. Currentvoltage characteristics of a Tour wire and a new molecular rectifier are presented.

  3. Current noise in tunnel junctions

    Energy Technology Data Exchange (ETDEWEB)

    Frey, Moritz; Grabert, Hermann [Physikalisches Institut, Universitaet Freiburg, Hermann-Herder-Strasse 3, 79104, Freiburg (Germany)

    2017-06-15

    We study current fluctuations in tunnel junctions driven by a voltage source. The voltage is applied to the tunneling element via an impedance providing an electromagnetic environment of the junction. We use circuit theory to relate the fluctuations of the current flowing in the leads of the junction with the voltage fluctuations generated by the environmental impedance and the fluctuations of the tunneling current. The spectrum of current fluctuations is found to consist of three parts: a term arising from the environmental Johnson-Nyquist noise, a term due to the shot noise of the tunneling current and a third term describing the cross-correlation between these two noise sources. Our phenomenological theory reproduces previous results based on the Hamiltonian model for the dynamical Coulomb blockade and provides a simple understanding of the current fluctuation spectrum in terms of circuit theory and properties of the average current. Specific results are given for a tunnel junction driven through a resonator. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.

    1993-01-01

    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc bias...

  5. Intra-epithelially entrapped blood vessels in ameloblastoma.

    Science.gov (United States)

    Siar, Chong Huat; Ishak, Ismadi; Ng, Kok Han

    2015-05-01

    The ameloblastoma is a benign but locally aggressive odontogenic neoplasm with a high recurrence rate. While significant progress has been made in our understanding regarding the role of tumoral vasculature relative to the diverse behavioral characteristics of this tumor, no attention has been paid to a distinct subset of blood vessels entrapped within its epithelial compartment. As vascular niches are known to influence tumoral growth, clarification of these vessels is important. The objectives of this study were to investigate the morphologic characteristics of intra-epithelially entrapped blood vessels (IEBVs) in ameloblastoma and to speculate on their relevance. Here, we evaluated the frequency, microvessel density (MVD), morphology, and distribution pattern of IEBVs in 77 ameloblastoma of different subtypes based on their immunoreactivity for endothelial markers (CD34, CD31, CD105), vascular tight junction protein (claudin-5), pericyte [α-smooth muscle actin (α-sma)], and vascular basement membrane (collagen IV). IEBVs were heterogeneously detected in ameloblastoma. Their mean MVD (CD34 = 15.46 ± 7.25; CD31 = 15.8 ± 5.04; CD105 = 0.82 ± 0.51) showed no significant correlation with different subtypes, and between primary and recurrent tumors (P > 0.05). These microvessels may occur as single/clusters of capillary sprouts, or formed compressed branching/non-branching slits entrapped within the epithelial compartment, and in direct apposition with polyhedral/granular neoplastic epithelial cells. They expressed proteins for endothelial tight junctions (claudin-5-positive) and pericytes (α-sma-positive) but had deficient basement membrane (collagen IV weak to absent). Aberrant expression for CD34, CD31, and CD105 in tumor epithelium was variably observed. Although rare in occurrence, identification of IEBVs in ameloblastoma could potentially represent a new paradigm for vascular assessment of this neoplasm. © 2014 John Wiley & Sons A/S. Published by John

  6. Effect of Helicobacter pylori on gastric epithelial cells

    Science.gov (United States)

    Alzahrani, Shatha; Lina, Taslima T; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E

    2014-01-01

    The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world’s population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori’s avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori. PMID:25278677

  7. Airway Epithelial Cell Integrity Protects from Cytotoxicity of Pseudomonas aeruginosa Quorum-Sensing Signals.

    Science.gov (United States)

    Losa, Davide; Köhler, Thilo; Bacchetta, Marc; Saab, Joanna Bou; Frieden, Maud; van Delden, Christian; Chanson, Marc

    2015-08-01

    Cell-to-cell communication via gap junctions regulates airway epithelial cell homeostasis and maintains the epithelium host defense. Quorum-sensing molecules produced by Pseudomonas aeruginosa coordinate the expression of virulence factors by this respiratory pathogen. These bacterial signals may also incidentally modulate mammalian airway epithelial cell responses to the pathogen, a process called interkingdom signaling. We investigated the interactions between the P. aeruginosa N-3-oxo-dodecanoyl-L-homoserine lactone (C12) quorum-sensing molecule and human airway epithelial cell gap junctional intercellular communication (GJIC). C12 degradation and its effects on cells were monitored in various airway epithelial cell models grown under nonpolarized and polarized conditions. Its concentration was further monitored in daily tracheal aspirates of colonized intubated patients. C12 rapidly altered epithelial integrity and decreased GJIC in nonpolarized airway epithelial cells, whereas other quorum-sensing molecules had no effect. The effects of C12 were dependent on [Ca(2+)]i and could be prevented by inhibitors of Src tyrosine family and Rho-associated protein kinases. In contrast, polarized airway cells grown on Transwell filters were protected from C12 except when undergoing repair after wounding. In vivo during colonization of intubated patients, C12 did not accumulate, but it paralleled bacterial densities. In vitro C12 degradation, a reaction catalyzed by intracellular paraoxonase 2 (PON2), was impaired in nonpolarized cells, whereas PON2 expression was increased during epithelial polarization. The cytotoxicity of C12 on nonpolarized epithelial cells, combined with its impaired degradation allowing its accumulation, provides an additional pathogenic mechanism for P. aeruginosa infections.

  8. Mammary epithelial cell

    DEFF Research Database (Denmark)

    Kass, Laura; Erler, Janine Terra; Dembo, Micah

    2007-01-01

    a repertoire of transmembrane receptors, of which integrins are the best characterized. Integrins modulate cell fate by reciprocally transducing biochemical and biophysical cues between the cell and the extracellular matrix, facilitating processes such as embryonic branching morphogenesis and lactation...... in the mammary gland. During breast development and cancer progression, the extracellular matrix is dynamically altered such that its composition, turnover, processing and orientation change dramatically. These modifications influence mammary epithelial cell shape, and modulate growth factor and hormonal...

  9. Oral focal epithelial hyperplasia.

    Science.gov (United States)

    López-Jornet, Pía; Camacho-Alonso, Fabio; Berdugo, Lucero

    2010-01-01

    Focal epithelial hyperplasia (FEH) is a benign, asymptomatic disease. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue and, less frequently, on the upper lip, gingiva and palate. FEH is caused by human papillomavirus subtype 13 or 32. The condition occurs in many populations and ethnic groups. We present the clinical case of a 31-year-old male with lesions that clinically and histologically corresponded to FEH.

  10. Stability of large-area molecular junctions

    NARCIS (Netherlands)

    Akkerman, Hylke B.; Kronemeijer, Auke J.; Harkema, Jan; van Hal, Paul A.; Smits, Edsger C. P.; de Leeuw, Dago M.; Blom, Paul W. M.

    The stability of molecular junctions is crucial for any application of molecular electronics. Degradation of molecular junctions when exposed to ambient conditions is regularly observed. In this report the stability of large-area molecular junctions under ambient conditions for more than two years

  11. Soliton bunching in annular Josephson junctions

    DEFF Research Database (Denmark)

    Vernik, I.V; Lazarides, Nickos; Sørensen, Mads Peter

    1996-01-01

    By studying soliton (fluxon) motion in long annular Josephson junctions it is possible to avoid the influence of the boundaries and soliton-soliton collisions present in linear junctions. A new experimental design consisting of a niobium coil placed on top of an annular junction has been used...

  12. Long Range Magnetic Interaction between Josephson Junctions

    DEFF Research Database (Denmark)

    Grønbech-Jensen, Niels; Samuelsen, Mogens Rugholm

    1995-01-01

    A new model for magnetic coupling between long Josephson junctions is proposed. The coupling mechanism is a result of the magnetic fields outside the junctions and is consequently effective over long distances between junctions. We give specific expressions for the form and magnitude of the inter...

  13. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.;

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...

  14. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...

  15. Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

    Energy Technology Data Exchange (ETDEWEB)

    Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.; Parkos, Charles A. [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States); Nusrat, Asma, E-mail: anusrat@emory.edu [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States)

    2010-07-02

    The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors or siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.

  16. Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Joseph U Igietseme

    Full Text Available Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up-regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1, but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43, Mets1, Add1Scarb1 and MARCKSL1. T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of

  17. Immunohistochemical and oncogenetic analyses of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas.

    Science.gov (United States)

    Imamhasan, Abdukadir; Mitomi, Hiroyuki; Saito, Tsuyoshi; Hayashi, Takuo; Takahashi, Michiko; Kajiyama, Yoshiaki; Yao, Takashi

    2012-11-01

    Basaloid squamous cell carcinoma of the esophagus is a rare variant of squamous cell carcinoma. We reviewed 878 cases of esophageal squamous cell carcinoma and detected 22 cases (3%) of basaloid squamous cell carcinoma. These tumors and stage-matched paired conventional squamous cell carcinomas were investigated for clinicopathologic features and immunoreactivity of cytokeratin subtypes, p53, B-cell lymphoma 2 (bcl-2), β-catenin, and epidermal growth factor receptor. Molecular aberrations in p53, CTNNB1 (the gene encoding β-catenin), and epidermal growth factor receptor (EGFR) were also determined. Patients with basaloid squamous cell carcinomas demonstrated a 5-year survival rate of 42%, significantly worse than those with well-differentiated squamous cell carcinoma (Pcarcinomas, the basaloid squamous cell carcinomas were less immunoreactive for cytokeratin 14, cytokeratin 903, and membranous β-catenin (Pcarcinomas, low-level expression of cytokeratin 14/cytokeratin 903 and mutations of p53 and EGFR had a significant influence on worse survival (Pcarcinoma, a neoplasm with particularly aggressive biologic behavior, should be differentiated from conventional squamous cell carcinomas. In this context, immunohistochemical assessment of several markers might provide a useful adjunct diagnostic tool. Aberrations of p53 and epidermal growth factor receptor genes are possibly involved in progression of esophageal basaloid squamous cell carcinoma.

  18. Shear Stress-Induced Alteration of Epithelial Organization in Human Renal Tubular Cells.

    Directory of Open Access Journals (Sweden)

    Damien Maggiorani

    Full Text Available Tubular epithelial cells in the kidney are continuously exposed to urinary fluid shear stress (FSS generated by urine movement and recent in vitro studies suggest that changes of FSS could contribute to kidney injury. However it is unclear whether FSS alters the epithelial characteristics of the renal tubule. Here, we evaluated in vitro and in vivo the influence of FSS on epithelial characteristics of renal proximal tubular cells taking the organization of junctional complexes and the presence of the primary cilium as markers of epithelial phenotype. Human tubular cells (HK-2 were subjected to FSS (0.5 Pa for 48 h. Control cells were maintained under static conditions. Markers of tight junctions (Claudin-2, ZO-1, Par polarity complex (Pard6, adherens junctions (E-Cadherin, β-Catenin and the primary cilium (α-acetylated Tubulin were analysed by quantitative PCR, Western blot or immunocytochemistry. In response to FSS, Claudin-2 disappeared and ZO-1 displayed punctuated and discontinuous staining in the plasma membrane. Expression of Pard6 was also decreased. Moreover, E-Cadherin abundance was decreased, while its major repressors Snail1 and Snail2 were overexpressed, and β-Catenin staining was disrupted along the cell periphery. Finally, FSS subjected-cells exhibited disappeared primary cilium. Results were confirmed in vivo in a uninephrectomy (8 months mouse model where increased FSS induced by adaptive hyperfiltration in remnant kidney was accompanied by both decreased epithelial gene expression including ZO-1, E-cadherin and β-Catenin and disappearance of tubular cilia. In conclusion, these results show that proximal tubular cells lose an important number of their epithelial characteristics after long term exposure to FSS both in vitro and in vivo. Thus, the changes in urinary FSS associated with nephropathies should be considered as potential insults for tubular cells leading to disorganization of the tubular epithelium.

  19. Butyrate Enhances the Intestinal Barrier by Facilitating Tight Junction Assembly via Activation of AMP-Activated Protein Kinase in Caco-2 Cell Monolayers12

    Science.gov (United States)

    Peng, Luying; Li, Zhong-Rong; Green, Robert S.; Holzman, Ian R.; Lin, Jing

    2009-01-01

    Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier. PMID:19625695

  20. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.

    Science.gov (United States)

    Peng, Luying; Li, Zhong-Rong; Green, Robert S; Holzman, Ian R; Lin, Jing

    2009-09-01

    Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier.

  1. Calcifying epithelial odontogenic tumor: a clinico-radio-pathological dilemma.

    Science.gov (United States)

    Hada, M S; Sable, M; Kane, S V; Pai, Prathamesh S; Juvekar, S L

    2014-01-01

    The calcifying epithelial odontogenic tumor (CEOT) is a rare benign neoplasm of mandible in adults. The presentation of this entity is varied and often confused with a variety of mucosal and jaw lesions and clinical, radiological, and pathological feature of CEOT often-mimic malignancy. The objective of this report is to highlight the clinical features and radiological findings which should arouse suspicion of a benign lesion and importance of providing adequate clinical information to the pathologist to attain accurate diagnosis.We discussed two cases with tumors located in the maxilla. Both presented as expansile lesions with one biopsy proven squamous cell carcinoma. Both were pursued with clinico-radiological suspicion of benign lesions and confirmed with pathological correlation of histology and immunohistochemistry as CEOT. Therefore a High index of suspicion and clinico-radiological information are the key feature for diagnosis of this rare tumor.

  2. Radiographic study on oral malignant tumors of epithelial tissue origin

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seung Don; Kim, Jae Duck [Dept. of Oral Radiology, College of Dentistry, Chosun University, Kwangju (Korea, Republic of)

    1993-02-15

    The author analyzed the clinical and radiographic findings of 109 malignant tumors of epithelial origin occurred in the jaws of the patients visited the infirmaries of Dentistry, Chosun University and several university in Korea during 1978 to 1988. The observed results were as follows: 1. It appeared that 93% of the total 397 cases diagnosed as oral malignant tumors were squamous cell carcinomas. 2. The incidence ratios between nodular type and ulcer type were 4 to 1 in maxilla and 3 to 1 mandible. 3. In nearly 50% of all patients complained of pain due to impingement of tumor mass or ulcer. 4. Most of carcinomas of maxila eventually invaded into maxillary sinus and palate. 5. Characteristic features on the radiographs were the lesion with ill-defined border, the direct destruction of the alveolar bone and anatomical landmark without displacement of the involved teeth and the gray shadow of the tumor mass in the lesion.

  3. Octagonal Defects at Carbon Nanotube Junctions

    Directory of Open Access Journals (Sweden)

    W. Jaskólski

    2013-01-01

    Full Text Available We investigate knee-shaped junctions of semiconductor zigzag carbon nanotubes. Two dissimilar octagons appear at such junctions; one of them can reconstruct into a pair of pentagons. The junction with two octagons presents two degenerate localized states at Fermi energy (EF. The reconstructed junction has only one state near EF, indicating that these localized states are related to the octagonal defects. The inclusion of Coulomb interaction splits the localized states in the junction with two octagons, yielding an antiferromagnetic system.

  4. Fabrication of high quality ferromagnetic Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Weides, M. [Institute for Solid State Research, Research Centre Juelich, D-52425 Juelich (Germany) and CNI-Center of Nanoelectronic Systems for Information Technology, Research Centre Juelich, D-52425 Juelich (Germany)]. E-mail: m.weides@fz-juelich.de; Tillmann, K. [Institute for Solid State Research, Research Centre Juelich, D-52425 Juelich (Germany); Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons, Research Centre Juelich, D-52425 Juelich (Germany); Kohlstedt, H. [Institute for Solid State Research, Research Centre Juelich, D-52425 Juelich (Germany); CNI-Center of Nanoelectronic Systems for Information Technology, Research Centre Juelich, D-52425 Juelich (Germany); Department of Material Science and Engineering and Department of Physics, University of Berkeley, CA 94720 (United States)

    2006-05-15

    We present ferromagnetic Nb/Al{sub 2}O{sub 3}/Ni{sub 60}Cu{sub 40}/Nb Josephson junctions (SIFS) with an ultrathin Al{sub 2}O{sub 3} tunnel barrier. The junction fabrication was optimized regarding junction insulation and homogeneity of current transport. Using ion-beam-etching and anodic oxidation we defined and insulated the junction mesas. The additional 2 nm thin Cu-layer below the ferromagnetic NiCu (SINFS) lowered interface roughness and ensured very homogeneous current transport. A high yield of junctional devices with j {sub c} spreads less than 2% was obtained.

  5. Examination of the Restoration of Epithelial Barrier Function Following Superficial Keratectomy

    OpenAIRE

    Hutcheon, Audrey E. K.; Sippel, Kimberly C.; Zieske, James D.

    2006-01-01

    The goal of the present study was to determine the rate of restoration of the corneal epithelial barrier following a superficial keratectomy using a functional assay of tight junction integrity. Adult Sprague-Dawley rats were anesthetized and a 3-mm superficial keratectomy was performed. The eyes were allowed to heal from 4 hours to 8 weeks and the rate of epithelial wound closure was determined. To examine the restoration of the barrier function, EZ-Link Sulfo-NHS-LC-Biotin (LC-Biotin) was a...

  6. Squamous cell carcinoma of the anal sacs in three dogs.

    Science.gov (United States)

    Mellett, S; Verganti, S; Murphy, S; Bowlt, K

    2015-03-01

    Anal sac squamous cell carcinoma is rare in dogs. Five cases have been previously reported, treatment of which involved surgery alone. This report describes three further cases of canine anal sac squamous cell carcinoma which underwent medical (meloxicam) management alone, resulting in survival of up to seven months. No metastases were identified. Squamous cell carcinoma, although extremely uncommon, should be considered as a possible differential diagnosis when a dog is presented for investigation of an anal sac mass.

  7. Penile squamous cell carcinoma arising from balanitis xerotica obliterans.

    Science.gov (United States)

    Pride, H B; Miller, O F; Tyler, W B

    1993-09-01

    Squamous cell carcinoma arising from balanitis xerotica obliterans is rarely reported. We describe an 83-year-old man in whom metastatic penile squamous cell carcinoma developed after 18 years of observation for balanitis xerotica obliterans. It is important to recognize the possibility of this uncommon complication of balanitis xerotica obliterans, because survival of patients with squamous cell carcinoma depends on early diagnosis and treatment.

  8. Squamous cell carcinoma in situ after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kambara, Takeshi; Nishiyama, Takafumi; Yamada, Rie; Nagatani, Tetsuo; Nakajima, Hiroshi [Yokohama City Univ. (Japan). School of Medicine; Sugiyama, Asami

    1997-12-31

    We report two cases with Squamous Cell Carcinoma (SCC) in situ caused by irradiation to hand eczemas, resistant to any topical therapies. Both of our cases clinically show palmer sclerosis and flexor restriction of the fingers, compatible to chronic radiation dermatitis. Although SCC arising in chronic radiation dermatitis is usually developed ten to twenty years after irradiation, in our cases SCC were found more than forty years after irradiation. (author)

  9. Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions.

    Science.gov (United States)

    Raleigh, David R; Marchiando, Amanda M; Zhang, Yong; Shen, Le; Sasaki, Hiroyuki; Wang, Yingmin; Long, Manyuan; Turner, Jerrold R

    2010-04-01

    In vitro studies have demonstrated that occludin and tricellulin are important for tight junction barrier function, but in vivo data suggest that loss of these proteins can be overcome. The presence of a heretofore unknown, yet related, protein could explain these observations. Here, we report marvelD3, a novel tight junction protein that, like occludin and tricellulin, contains a conserved four-transmembrane MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. Phylogenetic tree reconstruction; analysis of RNA and protein tissue distribution; immunofluorescent and electron microscopic examination of subcellular localization; characterization of intracellular trafficking, protein interactions, dynamic behavior, and siRNA knockdown effects; and description of remodeling after in vivo immune activation show that marvelD3, occludin, and tricellulin have distinct but overlapping functions at the tight junction. Although marvelD3 is able to partially compensate for occludin or tricellulin loss, it cannot fully restore function. We conclude that marvelD3, occludin, and tricellulin define the tight junction-associated MARVEL protein family. The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation.

  10. Clinicopathologic Features of Advanced Squamous NSCLC.

    Science.gov (United States)

    Socinski, Mark A; Obasaju, Coleman; Gandara, David; Hirsch, Fred R; Bonomi, Philip; Bunn, Paul; Kim, Edward S; Langer, Corey J; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Spigel, David R; Stinchcombe, Thomas E; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-09-01

    Lung cancer remains the leading cause of cancer-related death worldwide. NSCLC accounts for more than 85% of all lung cancers, and the prognosis for advanced-stage disease is typically poor. In recent years, the importance of histologic subtypes of NSCLC has been recognized, and the distinction between squamous and other NSCLC histologic subtypes is now critical to patient management. Squamous cell lung cancer (sqCLC) represents approximately 25% to 30% of NSCLC. The prognosis for patients with advanced NSCLC is poorer for those with sqCLC than for those with adenocarcinoma. This is partly due to a number of clinical characteristics that distinguish sqCLC from other NSCLC histologic subtypes, such as smoking history, comorbid diseases, age, and molecular profile. Together, these factors make sqCLC an especially challenging disease to manage. Herein, we review some of the key clinicopathologic features of sqCLC. Understanding these features to optimally address many of the unique therapeutic challenges of this disease is likely to be central to ultimately improving outcomes for patients with squamous NSCLC.

  11. Intradural squamous cell carcinoma in the sacrum

    Directory of Open Access Journals (Sweden)

    Fujisawa Kozo

    2009-02-01

    Full Text Available Abstract Background Leptomeningeal carcinomatosis occurs in patients with cancer at the rate of approximately 5%; it develops particularly in patients with breast cancer, lung cancer, melanoma, leukemia, or malignant lymphoma. We describe a rare case of leptomeningeal carcinomatosis in which spinal intradural squamous cell carcinoma with no lesions in the cerebral meninges and leptomeninx, was the primary lesion. Methods A 64-year-old man complained of sacral pain. Although the patient was treated with analgesics, epidural block and nerve root block, sacral pain persisted. Since acute urinary retention occurred, he was operated on. The patient was diagnosed as having an intradural squamous cell carcinoma of unknown origin. Results Since the patient presented with a slightly decreased level of consciousness 2 months after surgery, he was subjected to MRI scanning of the brain and spinal cord, which revealed disseminated lesions in the medulla oblongata. The patient died of pneumonia and sepsis caused by methicillin-resistant Staphylococcus aureus 5 months after surgery. Conclusion We report the first case of a patient with intradural squamous cell carcinoma with unknown origin that developed independently in the sacrum.

  12. Immunohistochemical characterization of mammary squamous cell carcinoma of the dog.

    Science.gov (United States)

    Sassi, Francesco; Sarli, Giuseppe; Brunetti, Barbara; Morandi, Federico; Benazzi, Cinzia

    2008-11-01

    Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin.

  13. Selective permeability of gap junction channels.

    Science.gov (United States)

    Goldberg, Gary S; Valiunas, Virginijus; Brink, Peter R

    2004-03-23

    Gap junctions mediate the transfer of small cytoplasmic molecules between adjacent cells. A family of gap junction proteins exist that form channels with unique properties, and differ in their ability to mediate the transfer of specific molecules. Mutations in a number of individual gap junction proteins, called connexins, cause specific human diseases. Therefore, it is important to understand how gap junctions selectively move molecules between cells. Rules that dictate the ability of a molecule to travel through gap junction channels are complex. In addition to molecular weight and size, the ability of a solute to transverse these channels depends on its net charge, shape, and interactions with specific connexins that constitute gap junctions in particular cells. This review presents some data and interpretations pertaining to mechanisms that govern the differential transfer of signals through gap junction channels.

  14. Interferon γ-Induced Nuclear Interleukin-33 Potentiates the Release of Esophageal Epithelial Derived Cytokines.

    Directory of Open Access Journals (Sweden)

    Jing Shan

    Full Text Available Esophageal epithelial cells are an initiating cell type in esophageal inflammation, playing an essential role in the pathogenesis of gastroesophageal reflux disease (GERD. A new tissue-derived cytokine, interleukin-33 (IL-33, has been shown to be upregulated in esophageal epithelial cell nuclei in GERD, taking part in mucosal inflammation. Here, inflammatory cytokines secreted by esophageal epithelial cells, and their regulation by IL-33, were investigated.In an in vitro stratified squamous epithelial model, IL-33 expression was examined using quantitative RT-PCR, western blot, ELISA, and immunofluorescence. Epithelial cell secreted inflammatory cytokines were examined using multiplex flow immunoassay. IL-33 was knocked down with small interfering RNA (siRNA in normal human esophageal epithelial cells (HEECs. Pharmacological inhibitors and signal transducers and activators of transcription 1 (STAT1 siRNA were used to explore the signaling pathways.Interferon (IFNγ treatment upregulated nuclear IL-33 in HEECs. Furthermore, HEECs can produce various inflammatory cytokines, such as IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1, regulated on activation normal T-cell expressed and presumably secreted (RANTES, and granulocyte-macrophage colony-stimulating factor (GM-CSF in response to IFNγ. Nuclear, but not exogenous IL-33, amplified IFN induction of these cytokines. P38 mitogen-activated protein kinase (MAPK and janus protein tyrosine kinases (JAK/STAT1 were the common signaling pathways of IFNγ-mediated induction of IL-33 and other cytokines.Esophageal epithelial cells can actively participate in GERD pathogenesis through the production of various cytokines, and epithelial-derived IL-33 might play a central role in the production of these cytokines.

  15. Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Toki, Hideaki; Minowa, Osamu; Inoue, Maki; Motegi, Hiromi; Karashima, Yuko; Ikeda, Ami [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Kaneda, Hideki [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Sakuraba, Yoshiyuki [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Saiki, Yuriko [Department of Molecular Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi (Japan); Wakana, Shigeharu [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Suzuki, Hiroshi [Department of Biochemistry, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Gondo, Yoichi [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Shiroishi, Toshihiko [Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka (Japan); Noda, Tetsuo, E-mail: tnoda@jfcr.or.jp [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo (Japan)

    2016-08-05

    Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1–4] and humans to Darier disease (DD) [14–17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162). Molecular analysis showed no aberration in Serca2 mRNA or protein expression levels in normal esophageal cells of any of the four mutant heterozygotes. There was no loss of heterozygosity at the Serca2 locus in the squamous cell carcinomas in any of the four lines. The effect of each mutation on Ca{sup 2+}-ATPase activity was predicted using atomic-structure models and accumulated mutated protein studies, suggesting that putative complete loss of Serca2 enzymatic activity may lead to early tumor onset, whereas mutations in which Serca2 retains residual enzymatic activity result in late onset. We propose that impaired Serca2 gene product activity has a long-term effect on squamous cell carcinogenesis from onset to the final carcinoma stage through an as-yet unrecognized but common regulatory pathway. -- Highlights: •Novel mutations in murine Serca2 caused early onset or late onset of tumorigenesis. •They also caused higher or lower incidence of Darier Disease phenotype. •3D structure model suggested the former mutations led to severer defect on ATPase. •Driver gene mutations via long-range effect on Ca2+ distributions are suggested.

  16. Detection of papillomaviral DNA sequences in a feline oral squamous cell carcinoma.

    Science.gov (United States)

    Munday, J S; Howe, L; French, A; Squires, R A; Sugiarto, H

    2009-04-01

    Oral squamous cell carcinomas (OSCCs) are common and often fatal feline neoplasms. Factors that predispose to neoplasm development in cats are poorly defined. Around 25% of human OSCCs are caused by papillomaviruses (PVs). To determine if PVs are associated with OSCCs in cats, three sets of consensus primers were used to evaluate 20 feline OSCCs and 20 non-neoplastic feline oral lesions for the presence of PV DNA. Papillomaviral sequences were detected within one OSCC, but no non-neoplastic lesion. Sequencing of the amplified DNA revealed a previously unreported PV that was most similar to human PV type 76. This is the first time PV DNA has been amplified from the oral cavity of a cat. However, while these results suggest that feline gingival epithelial cells can be infected by PVs, they do not support a causal association between viral infection and the development of feline OSCCs.

  17. Multicentric Squamous Odontogenic Tumor: A Case Report and Review of the Literature.

    Science.gov (United States)

    Elmuradi, Sophia; Mair, Yasmin; Suresh, Lakshmanan; DeSantis, James; Neiders, Mirdza; Aguirre, Alfredo

    2016-09-08

    Squamous odontogenic tumor (SOT) is a rare benign epithelial odontogenic neoplasm of the jaws. Both intraosseous and peripheral SOTs have been described in the English language literature. While most intraosseous SOTs occur as solitary lesions, a multicentric variant has also been previously described. Although the radiographic and microscopic features are identical for both solitary and multicentric clinical presentations, there are three significant differences between them. More specifically, multicentric SOT presents at an earlier age (third decade of life), has a slightly higher male to female ratio than the solitary type and has a marked predilection for African-Americans. Here we document the eighth reported case of multicentric SOT, which was diagnosed in a 43-year-old African-American male. In addition, we feature focal sebaceous metaplasia, a heretofore unknown microscopic feature of SOT. Clinical, radiological, and histopathological findings are discussed. The differential diagnosis, biological behavior and management modalities for SOT are also addressed.

  18. Seebeck effect in molecular junctions

    Science.gov (United States)

    Zimbovskaya, Natalya A.

    2016-05-01

    Advances in the fabrication and characterization of nanoscale systems presently allow for a better understanding of their thermoelectric properties. As is known, the building blocks of thermoelectricity are the Peltier and Seebeck effects. In the present work we review results of theoretical studies of the Seebeck effect in single-molecule junctions and similar systems. The behavior of thermovoltage and thermopower in these systems is controlled by several factors including the geometry of molecular bridges, the characteristics of contacts between the bridge and the electrodes, the strength of the Coulomb interactions between electrons on the bridge, and of electron-phonon interactions. We describe the impact of these factors on the thermopower. Also, we discuss a nonlinear Seebeck effect in molecular junctions.

  19. Electron transport in molecular junctions

    DEFF Research Database (Denmark)

    Jin, Chengjun

    This thesis addresses the electron transport in molecular junctions, focusing on the energy level alignment and correlation effects. Various levels of theory have been applied to study the structural and electronic effects in different molecular junctions, starting from the single particle density...... charge position are in quantitative agreement with the experiments, while pure DFT is not. This is the consequence of the accurate energy level alignment, where the DFT+∑ method corrects the self-interaction error in the standard DFT functional and uses a static image charge model to include the image...... charge effect on the energy level renormalization. Additionally, the gating of the 4,4’-bipyridine (44BP) molecule contacted to either Ni or Au electrodes has been investigated. Here it is found that the gating mechanism is conceptually different between two cases. In the case of Ni contacts where...

  20. How coherent are Josephson junctions?

    CERN Document Server

    Paik, Hanhee; Bishop, Lev S; Kirchmair, G; Catelani, G; Sears, A P; Johnson, B R; Reagor, M J; Frunzio, L; Glazman, L; Schoelkopf, R J

    2011-01-01

    Attaining sufficient coherence is a requirement for realizing a large-scale quantum computer. We present a new implementation of a superconducting transmon qubit that is strongly coupled to a three-dimensional superconducting cavity. We observe a reproducible increase in the coherence times of qubit (both $T_1$ and $T_2$ > 10 microseconds) and cavity ($T_{cav}$ ~ 50 microseconds) by more than an order of magnitude compared to the current state-of-art superconducting qubits. This enables the study of the stability and quality of Josephson junctions at precisions exceeding one part per million. Surprisingly, we see no evidence for $1/f$ critical current noise. At elevated temperatures, we observe the dissipation due to a small density (< 1 - 10 ppm) of thermally-excited quasiparticles. The results suggest that the overall quality of Josephson junctions will allow error rates of a few $10^{-4}$, approaching the error correction threshold.

  1. Morphogenesis of rat myotendinous junction.

    Science.gov (United States)

    Curzi, Davide; Ambrogini, Patrizia; Falcieri, Elisabetta; Burattini, Sabrina

    2013-10-01

    Myotendinous junction (MTJ) is the highly specialized complex which connects the skeletal muscle to the tendon for transmitting the contractile force between the two tissues. The purpose of this study was to investigate the MTJ development and rat EDL was chosen as a model. 1, 15, 30 day animals were considered and the junctions were analyzed by light and electron microscopy. The MTJ interface architecture increased during the development, extending the interaction between muscle and tendon. 1-day-old rats showed disorganized myofibril bundles, spread cytosol and incomplete rough endoplasmic reticulum, features partially improved in 15-day-old rats, and completely developed in 30-day-old animals. These findings indicate that muscle-tendon interface displays, during rat lifetime, numerically increased and longer tendon interdigitations, correlated with an improved organization of both tissues and with a progressive acquirement of full functionality.

  2. Cutaneous squamous cell carcinoma manifesting as follicular isthmus cysts in a cat

    Directory of Open Access Journals (Sweden)

    Elizabeth A Layne

    2016-01-01

    Full Text Available Case summary A 9-year-old spayed female domestic shorthair cat was examined for swelling of the right upper lip. The cat had been receiving oral ciclosporin A for eosinophilic plaques. The swelling appeared clinically and cytologically consistent with an abscess; exudate was cultured and treatment consisted of antibiotic therapy and surgical curettage. Five months of antibiotic therapy with three separate surgical treatments resulted in minimal improvement; three separate biopsy samples demonstrated epithelial cysts with severe dermal inflammation. Swelling and drainage of purulent material from the affected lip persisted and progressed to involve the left upper lip. Euthanasia was elected 13 months after initial examination due to disease progression. On necropsy, histopathology demonstrated multiple isthmus cysts intermixed with squamous cell carcinoma (SCC. Relevance and novel information The clinical and histopathologic features were unusual for feline cutaneous SCC. The cystic nature and lack of epidermal involvement suggest the tumor arose from non-epidermal squamous cells such as follicular isthmus or ductal epithelium. There is a pattern of SCC recognized in human renal transplant patients with features of epidermal inclusion cysts. These features have not been previously reported in SCC from a cat.

  3. Expression and role of AQP1 in cervical squamous carcinoma and its precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To investigate the expression of aquaporin 1 in cervical squamous carcinomas (CSC) and cervical precancerous lesions, and the relationship between the tumor clinicopathological parameters, prognosis and the expression of AQP1. Methods: Immunohistochemical method (EliVision) was used to detect the expression of AQP1 in samples from 106 patients [20 with normal cervical tissue, 30 with cervical intraepithelial neoplasia (stage Ⅰ and Ⅱ) and 56 with CSC]. Survival analysis was performed by Kaplan-Meier method. Results: AQP1 protein was expressed in vascular endothelia of all samples. It showed upregulation of AQP1 expression in CSC. There was a significant difference between CSC and normal cervical tissues (P<0.05). AQP1 was expressed in some tumor cells and unexpressed in normal squamous epithelial cells. And APQ1-expressing tumor cells were positively related to lymph node metastasis. Patients with APQ1-expressing tumor cells had the lower survival rate than the ones without. Conclusion: Abnormal expression of AQP1 plays an important role in the development of CSC. Positive expression of AQP1 in tumor cells maybe enhances tumor metastasis and could be used as a marker for tumor prognosis.

  4. COPD and squamous cell lung cancer: aberrant inflammation and immunity is the common link.

    Science.gov (United States)

    Bozinovski, Steven; Vlahos, Ross; Anthony, Desiree; McQualter, Jonathan; Anderson, Gary; Irving, Louis; Steinfort, Daniel

    2016-02-01

    Cigarette smoking has reached epidemic proportions within many regions of the world and remains the highest risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Squamous cell lung cancer is commonly detected in heavy smokers, where the risk of developing lung cancer is not solely defined by tobacco consumption. Although therapies that target common driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related squamous cell lung cancer. Since COPD is characterized by an excessive inflammatory and oxidative stress response, this review details how aberrant innate, adaptive and systemic inflammatory processes can contribute to lung cancer susceptibility in COPD. Activated leukocytes release increasing levels of proteases and free radicals as COPD progresses and tertiary lymphoid aggregates accumulate with increasing severity. Reactive oxygen species promote formation of reactive carbonyls that are not only tumourigenic through initiating DNA damage, but can directly alter the function of regulatory proteins involved in host immunity and tumour suppressor functions. Systemic inflammation is also markedly increased during infective exacerbations in COPD and the interplay between tumour-promoting serum amyloid A (SAA) and IL-17A is discussed. SAA is also an endogenous allosteric modifier of FPR2 expressed on immune and epithelial cells, and the therapeutic potential of targeting this receptor is proposed as a novel strategy for COPD-lung cancer overlap.

  5. EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR AND HUMAN PAPILLOMAVIRUS (HPV L1 CAPSID PROTEIN IN CERVICAL SQUAMOUS INTRAEPITHELIAL LESIONS

    Directory of Open Access Journals (Sweden)

    Balan Raluca

    2010-09-01

    Full Text Available We analyzed the immunohistochemical pattern of epidermal growth factor receptor (EGFR in cervical squamous intraepithelial lesions (SILs in correlation with L1 HPV capsid protein, in order to determine the relationship between EGFR expression and the infection status of human papillomavirus (HPV. The study included 40 cases, 24 LSIL (low grade SIL (CIN1, cervical intraepithelial neoplasia and 16 HSIL (high grade SIL (6 cases of CIN2 and 10 cases of CIN3. The immunoexpression of L1 HPV protein was assessed on conventional cervico-vaginal smears and EGFR was immunohistochemically evaluated on the corresponding cervical biopsies. The HPV L1 capsid protein was expressed in 45.83% of LSIL and 25% of HSIL. EGFR was overexpressed in 62,4% of HSIL (58,4% CIN2 and 41,6% CIN3 and 37,6% LSIL. The immunoexpression of L1 HPV has clinical application in the progression assessment of the cervical precancerous lesions without a correlation to the grade of the cervical SIL. EGFR is expressed by all proliferating squamous epithelial cells, thus corresponding with the grade of SIL. The evaluation of EGFR status, correlated with L1 HPV protein expression, can provide useful data of progression risk of cervical squamous intraepithelial lesions

  6. Human corneal epithelial subpopulations

    DEFF Research Database (Denmark)

    Søndergaard, Chris Bath

    2013-01-01

    -free EpiLife medium, using a range of physiologically relevant oxygen concentrations (2%, 5%, 10%, 15% and 20%). Using immunocytochemistry and advanced fluorescence microscopy, cells were characterized regarding growth, cell cycle distribution, colony-forming efficiency (CFE), phenotypes...... and cytomorphometry. Limbal epithelial cells expanded in 2% O2 exhibited slow growth, low fraction of cells in S/G2 , high CFE, high expression of stem cell markers ABCG2 and p63α, and low fraction of differentiation marker CK3 resembling a LESC phenotype. The effect of hypoxia to maintain LESCs in culture...

  7. Epithelial cell polarity and tumorigenesis: new perspectives for cancer detection and treatment

    Institute of Scientific and Technical Information of China (English)

    Danila CORADINI; Claudia CASARSA; Saro ORIANA

    2011-01-01

    Loss of cell-cell adhesion and cell polarity is commonly observed in tumors of epithelial origin and correlates with their invasion into adjacent tissues and formation of metastases. Growing evidence indicates that loss of cell polarity and cell-cell adhesion may also be important in early stage of cancer. In first part of this review, we delineate the current understanding of the mechanisms that establish and maintain the polarity of epithelial tissues and discuss the involvement of cell polarity and apical junctional complex components in tumor pathogenesis. In the second part we address the clinical significance of cell polarity and junctional complex components in can- cer diagnosis and prognosis. Finally, we explore their potential use as therapeutic targets in the treatment of cancer.

  8. The Fanconi anemia pathway: Repairing the link between DNA damage and squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Romick-Rosendale, Lindsey E. [Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States); Lui, Vivian W.Y.; Grandis, Jennifer R. [Department of Otolaryngology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wells, Susanne I., E-mail: Susanne.Wells@cchmc.org [Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 (United States)

    2013-03-15

    Fanconi anemia (FA) is a rare inherited recessive disease caused by mutations in one of fifteen genes known to encode FA pathway components. In response to DNA damage, nuclear FA proteins associate into high molecular weight complexes through a cascade of post-translational modifications and physical interactions, followed by the repair of damaged DNA. Hematopoietic cells are particularly sensitive to the loss of these interactions, and bone marrow failure occurs almost universally in FA patients. FA as a disease is further characterized by cancer susceptibility, which highlights the importance of the FA pathway in tumor suppression, and will be the focus of this review. Acute myeloid leukemia is the most common cancer type, often subsequent to bone marrow failure. However, FA patients are also at an extreme risk of squamous cell carcinoma (SCC) of the head and neck and gynecological tract, with an even greater incidence in those individuals who have received a bone marrow transplant and recovered from hematopoietic disease. FA tumor suppression in hematopoietic versus epithelial compartments could be mechanistically similar or distinct. Definition of compartment specific FA activities is now critical to assess the effects of today's bone marrow failure treatments on tomorrow's solid tumor development. It is our hope that current therapies can then be optimized to decrease the risk of malignant transformation in both hematopoietic and epithelial cells. Here we review our current understanding of the mechanisms of action of the Fanconi anemia pathway as it contributes to stress responses, DNA repair and squamous cell carcinoma susceptibility.

  9. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dudás, József, E-mail: jozsef.dudas@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullár, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Romani, Angela, E-mail: angela.romani@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Pritz, Christian, E-mail: christian.pritz@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Hans Schartinger, Volker, E-mail: volker.schartinger@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Mathias Sprinzl, Georg, E-mail: georg.sprinzl@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: herbert.riechelmann@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

    2013-04-01

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.

  10. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zhang, Hongfang; Luo, Honglei; Jiang, Zhenzhen; Yue, Jing; Hou, Qiang; Xie, Ruifei; Wu, Shixiu

    2016-07-01

    The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  11. Influence of Ionizing Radiation on Stromal-Epithelial Communication in Esophageal Carcinogenesis

    Science.gov (United States)

    Huff, Janice; Patel, Zarana; Grugan, Katharine; Rustgi, Anil; Cucinotta, Francis A.

    Esophageal cancer is the 6th leading cause of cancer death worldwide and is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. A connection with ionizing radiation exposure is revealed by the high excess relative risk for esophageal squamous cell carcinoma observed in the survivors of the atomic bomb detonations in Japan. Esophageal carcinomas are also seen as secondary malignancies in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely responsive to treatment. In normal epithelium, the stromal microenvironment is essential for the maintenance and modulation of cell growth and differentiation. Cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibrob-lasts (Okawa et al., Genes Dev. 2007. 21: 2788-2803). We examined how irradiation of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. These assays were conducted in modified Boyden chambers using conditioned media from irradiated fibroblasts. Our results using low LET gamma radiation showed a dose-dependent increase in migration of epithelial

  12. Thermoelectric efficiency of molecular junctions

    Science.gov (United States)

    Perroni, C. A.; Ninno, D.; Cataudella, V.

    2016-09-01

    Focus of the review is on experimental set-ups and theoretical proposals aimed to enhance thermoelectric performances of molecular junctions. In addition to charge conductance, the thermoelectric parameter commonly measured in these systems is the thermopower, which is typically rather low. We review recent experimental outcomes relative to several junction configurations used to optimize the thermopower. On the other hand, theoretical calculations provide estimations of all the thermoelectric parameters in the linear and non-linear regime, in particular of the thermoelectric figure of merit and efficiency, completing our knowledge of molecular thermoelectricity. For this reason, the review will mainly focus on theoretical studies analyzing the role of not only electronic, but also of the vibrational degrees of freedom. Theoretical results about thermoelectric phenomena in the coherent regime are reviewed focusing on interference effects which play a significant role in enhancing the figure of merit. Moreover, we review theoretical studies including the effects of molecular many-body interactions, such as electron-vibration couplings, which typically tend to reduce the efficiency. Since a fine tuning of many parameters and coupling strengths is required to optimize the thermoelectric conversion in molecular junctions, new theoretically proposed set-ups are discussed in the conclusions.

  13. Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakagami

    2015-01-01

    Full Text Available 4H-1-benzopyran-4-ones (chromones are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E-3-(4-hydroxystyryl-6-methoxy-4H-chromen-4-one (compound 11, (E-6-methoxy-3-(4-methoxystyryl-4H-chromen-4-one (compound 4, (E-6-methoxy-3-(3,4,5-trimethoxystyryl-4H-chromen-4-one (compound 6 showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs.

  14. Transformation of the genital epithelial tract occurs early in California sea lion development.

    Science.gov (United States)

    Barragán-Vargas, Cecilia; Montano-Frías, Jorge; Ávila Rosales, Germán; Godínez-Reyes, Carlos R; Acevedo-Whitehouse, Karina

    2016-03-01

    An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly 'protective' effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions.

  15. Transformation of the genital epithelial tract occurs early in California sea lion development

    Science.gov (United States)

    Barragán-Vargas, Cecilia; Montano-Frías, Jorge; Ávila Rosales, Germán; Godínez-Reyes, Carlos R.; Acevedo-Whitehouse, Karina

    2016-01-01

    An unusually high prevalence of metastatic urogenital carcinoma has been observed in free-ranging California sea lions stranded off the coast of California in the past two decades. No cases have been reported for sea lions in the relatively unpolluted Gulf of California. We investigated occurrence of genital epithelial transformation in 60 sea lions (n=57 pups and 3 adult females) from the Gulf of California and examined whether infection by a viral pathogen previously found to be associated with urogenital carcinoma accounted for such alterations. We also explored the contribution of MHC class II gene expression on transformation. Cellular alterations, such as squamous cell atypia (ASC), atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions were observed in 42% of the pups and in 67% of the adult females. Normal genital epithelium was more common in male than female pups. ASC was five times more likely to occur in older pups. Epithelial alterations were unrelated to infection by the potentially oncogenic otarine type I gammaherpesvirus (OtHV-1), but ASCUS was more common in pups with marked and severe inflammation. Expression of MHC class II DRB loci (Zaca DRB-D) by peripheral antigen-presenting leucocytes showed a slightly ‘protective’ effect for ASC. We propose that transformation of the California sea lion genital epithelium is relatively common in young animals, increases with age and is probably the result of infection by an unidentified pathogen. Expression of a specific MHC class II gene, suggestive of presentation of specific antigenic peptides to immune effectors, appears to lower the risk of transformation. Our study provides the first evidence that epithelial transformation of the California sea lion genital tract is relatively common, even from an early age, and raises questions regarding differences in sea lion cancer-detection and -repair success between geographical regions. PMID:27069641

  16. Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter

    DEFF Research Database (Denmark)

    Herrmann, Susan; Seidelin, Michel; Bisgaard, Hanne Cathrine

    2002-01-01

    of the present study was to investigate the effect of ICZ on gap junctional intercellular communication (GJIC) in primary cultured rat hepatocytes co-cultured with the rat liver epithelial cell line WB-F344. Indolo[3,2-b]carbazole inhibited GJIC in the rat hepatocytes in a dose- and time-dependent manner...

  17. Expression of laminin-5 and integrins in actinic cheilitis and superficially invasive squamous cell carcinomas of the lip.

    Science.gov (United States)

    Peixoto da-Silva, Janaína; Lourenço, Silvia; Nico, Marcello; Silva, Filomena H; Martins, Marília Trierveiler; Costa-Neves, Adriana

    2012-10-15

    The progression of carcinogenesis entails the detachment of cells, invasion and migration of neoplastic cells. Alterations in epithelial adhesion and basement membrane proteins might mediate the early stages of carcinogenesis. This study investigated the expression of adhesion molecules and the basement membrane protein laminin-5 in actinic cheilitis (AC) and incipient squamous cell carcinoma of the lower lip to understand early photocarcinogenesis. Ln-5γ2 chain as well as α3, β1 subunits of α3β1 heterodimer and β4 subunit of integrin α6β4 were evaluated by immunohistochemistry in 16 cases of AC and 16 cases of superficially invasive squamous cell carcinoma (SISCC). Most AC cases showed reduced expression of β1, β4 and α3 integrins, and SISCCs lacked β1, β4 and α3 integrins in the invasive front. AC cases were negative for the Ln-5γ2 chain. Five cases of SISCC (31%) showed heterogeneous Ln-5γ2 chain expression in the invasive front of the tumor. Integrin β1, β4 and α3 expression is lost during the early stages of lip carcinogenesis. Expression of Ln-5γ2 in the invasive front in cases and its correlation with tumor progression suggest that it mediates the acquisition of the migrating and invading epithelial cell phenotype.

  18. Clinical evaluation of Lugol's iodine staining in the treatment of stage I-II squamous cell carcinoma of the tongue.

    Science.gov (United States)

    Umeda, M; Shigeta, T; Takahashi, H; Minamikawa, T; Komatsubara, H; Oguni, A; Shibuya, Y; Komori, T

    2011-06-01

    Oral squamous cell carcinoma (OSCC) is often surrounded by epithelial dysplasia; leaving it unresected can result in local recurrence. Staining with Lugol's iodine solution detects epithelial dysplasia in oral mucosa, but whether it decreases local recurrence after OSCC surgery is unknown. This study investigated local recurrence rates in patients with early tongue cancer who underwent surgery using Lugol's staining. 93 patients with T1-2N0 tongue SCC underwent partial glossectomy using Lugol's staining during surgery. Resection was performed at least 5mm from the margin of the unstained area. Patients were investigated retrospectively for local recurrence status. Postoperative histology revealed negative surgical margins for SCC or epithelial dysplasia in 81 patients, close margins for SCC in 5, positive margins for mild epithelial dysplasia in 6, and a positive margin for SCC in one. Those with a positive or a close margin for SCC underwent additional resection 2-4 weeks after surgery; one was proved histologically to have residual SCC. No patients developed local recurrence, but 2 died of neck metastasis and 2 of distant metastasis. The 5-year disease specific survival rate was 93.8%. Lugol's staining during surgery can reduce local recurrence and improve survival in patients with early tongue SCC.

  19. Salmonella infection upregulates the leaky protein claudin-2 in intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Yong-guo Zhang

    Full Text Available BACKGROUND: Tight junctions seal the space between adjacent epithelial cells. Mounting evidence suggests that tight junction proteins play a key role in the pathogenesis of human disease. Claudin is a member of the tight junction protein family, which has 24 members in humans. To regulate cellular function, claudins interact structurally and functionally with membrane and scaffolding proteins via their cytoplasmic domain. In particular, claudin-2 is known to be a leaky protein that contributes to inflammatory bowel disease and colon cancer. However, the involvement of claudin-2 in bacterial infection in the intestine remains unknown. METHODS/PRINCIPAL FINDINGS: We hypothesized that Salmonella elevates the leaky protein claudin-2 for its own benefit to facilitate bacterial invasion in the colon. Using a Salmonella-colitis mouse model and cultured colonic epithelial cells, we found that pathogenic Salmonella colonization significantly increases the levels of claudin-2 protein and mRNA in the intestine, but not that of claudin-3 or claudin-7 in the colon, in a time-dependent manner. Immunostaining studies showed that the claudin-2 expression along the crypt-villous axis postinfection. In vitro, Salmonella stimulated claudin-2 expression in the human intestinal epithelial cell lines SKCO15 and HT29C19A. Further analysis by siRNA knockdown revealed that claudin-2 is associated with the Salmonella-induced elevation of cell permeability. Epithelial cells with claudin-2 knockdown had significantly less internalized Salmonella than control cells with normal claudin-2 expression. Inhibitor assays demonstrated that this regulation is mediated through activation of the EGFR pathway and the downstream protein JNK. CONCLUSION/SIGNIFICANCE: We have shown that Salmonella targets the tight junction protein claudin-2 to facilitate bacterial invasion. We speculate that this disruption of barrier function contributes to a new mechanism by which bacteria interact

  20. The ectopic expression of Snail in MDBK cells does not induce epithelial-mesenchymal transition

    OpenAIRE

    IZAWA, GENYA; Kobayashi, Wakako; Haraguchi, Misako; Sudo, Akiharu; Ozawa, Masayuki

    2015-01-01

    Epithelial-mesenchymal transition (EMT), a key process in the tumor metastatic cascade, is characterized by the loss of cell-cell junctions and cell polarity, as well as by the acquisition of migratory and invasive properties. However, the precise molecular events that initiate this complex EMT process are poorly understood. Snail expression induces EMT in Madin-Darby canine kidney (MDCK) cells and the human epidermoid carcinoma cell line, A431. Snail is a zinc finger transcription factor and...

  1. Simple Epithelial Keratins.

    Science.gov (United States)

    Strnad, Pavel; Guldiken, Nurdan; Helenius, Terhi O; Misiorek, Julia O; Nyström, Joel H; Lähdeniemi, Iris A K; Silvander, Jonas S G; Kuscuoglu, Deniz; Toivola, Diana M

    2016-01-01

    Simple epithelial keratins (SEKs) are the cytoplasmic intermediate filament proteins of single-layered and glandular epithelial cells as found in the liver, pancreas, intestine, and lung. SEKs have broad cytoprotective functions, which are facilitated by dynamic posttranslational modifications and interaction with associated proteins. SEK filaments are composed of obligate heteropolymers of type II (K7, K8) and type I (K18-K20, K23) keratins. The multifaceted roles of SEKs are increasingly appreciated due to findings obtained from transgenic mouse models and human studies that identified SEK variants in several digestive diseases. Reorganization of the SEK network into aggregates called Mallory-Denk bodies (MDBs) is characteristic for specific liver disorders such as alcoholic and nonalcoholic steatohepatitis. To spur further research on SEKs, we here review the methods and potential caveats of their isolation as well as possibilities to study them in cell culture. The existing transgenic SEK mouse models, their advantages and potential drawbacks are discussed. The tools to induce MDBs, ways of their visualization and quantification, as well as the possibilities to detect SEK variants in humans are summarized. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Chaos induced by coupling between Josephson junctions

    Science.gov (United States)

    Shukrinov, Yu. M.; Azemtsa-Donfack, H.; Botha, A. E.

    2015-02-01

    It is found that, in a stack of intrinsic Josephson junctions in layered high temperature superconductors under external electromagnetic radiation, the chaotic features are triggered by interjunction coupling, i.e., the coupling between different junctions in the stack. While the radiation is well known to produce chaotic effects in the single junction, the effect of interjunction coupling is fundamentally different and it can lead to the onset of chaos via a different route to that of the single junction. A precise numerical study of the phase dynamics of intrinsic Josephson junctions, as described by the CCJJ+DC model, is performed. We demonstrate the charging of superconducting layers, in a bias current interval corresponding to a Shapiro step subharmonic, due to the creation of a longitudinal plasma wave along the stack of junctions. With increase in radiation amplitude chaotic behavior sets in. The chaotic features of the coupled Josephson junctions are analyzed by calculations of the Lyapunov exponents. We compare results for a stack of junctions to the case of a single junction and prove that the observed chaos is induced by the coupling between the junctions. The use of Shapiro step subharmonics may allow longitudinal plasma waves to be excited at low radiation power.

  3. [Remodeling of cardiac gap junctions and arrhythmias].

    Science.gov (United States)

    Yu, Zhi-Bin; Sheng, Juan-Juan

    2011-12-25

    In the heart, gap junctions mediate electrical and chemical coupling between adjacent cardiomyocytes, forming the cell-to-cell pathways for orderly spread of the wave of electrical excitation responsible for a functional syncytium. Three principal connexins are expressed in cardiomyocytes, connexin 43 (CX43), CX40, and CX45. CX43 predominates in ventricular muscle cells. Most of the gap junctions, assembled from CX43, are located at the intercalated discs, often with larger junctional plaques at the disc periphery. The gap junctions are rarely distributed to the sides of the cardiomyocyte. The ischemia-reperfusion, cardiac hypertrophy, heart failure, hypercholesterolemia, and diabetes mellitus induce gap junction remodeling. The gap junction remodeling induced by above-mentioned diseases shows similar characteristics, including down-regulation of CX43, reduction in gap junction plaque size, increased heterogeneity and lateralization of gap junction distribution, and dephosphorylation of CX43. The elevated angiotensin II concentration in local myocardium may play an important role in the gap junction remodeling. The down-regulation of CX43 and lateralization of gap junction distribution alter anisotropic spread of the impulse of ventricular myocardium. The dephosphorylation of CX43 not only reduces electrical conductance, but also decreases permeability of chemicals between cardiomyocytes. The lateralization of gap junctions may increase the number of hemichannels formed by CX43. The opening of hemichannels induces ATP efflux and Na(+) influx, which forms a delayed after-depolarization. The gap junction remodeling in pathological condition produces arrhythmia substrate in the ventricles. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and arrhythmias were summarized.

  4. Hot spices influence permeability of human intestinal epithelial monolayers.

    Science.gov (United States)

    Jensen-Jarolim, E; Gajdzik, L; Haberl, I; Kraft, D; Scheiner, O; Graf, J

    1998-03-01

    Indirect evidence suggests that hot spices may interact with epithelial cells of the gastrointestinal tract to modulate their transport properties. Using HCT-8 cells, a cell line from a human ileocoecal carcinoma, we studied the effects of spices on transepithelial electrical resistance (TER), permeability for fluorescein isothiocyanate (FITC)-labeled dextrans with graded molecular weight, and morphological alterations of tight junctions by immunofluorescence using an anti-ZO-1 antibody, a marker for tight junction integrity. Two different reactivity patterns were observed: paprika and cayenne pepper significantly decreased the TER and increased permeability for 10-, 20- and 40-kDa dextrans but not for -70 kDa dextrans. Simultaneously, tight junctions exhibited a discontinuous pattern. Applying extracts from black or green pepper, bay leaf or nutmeg increased the TER and macromolecular permeability remained low. Immunofluorescence ZO-1 staining was preserved. In accordance with the above findings, capsaicin transiently reduced resistance and piperine increased resistance, making them candidates for causing the effects seen with crude spice extracts. The observation that Solanaceae spices (paprika, cayenne pepper) increase permeability for ions and macromolecules might be of pathophysiological importance, particularly with respect to food allergy and intolerance.

  5. 病原微生物对紧密连接蛋白的调控%Regulation of pathogens on tight junction protein

    Institute of Scientific and Technical Information of China (English)

    张瑞丽; 王千秋

    2014-01-01

    Tight junctions are the structural and functional base of blood brain barrier and enteric epithelial barrier.Alterations of tight junctions play an important role in pathogens invading the body through paracellular penetration.The article reviews the progress on the effect of pathogens on the structure and function of tight junctions of blood brain barrier and enteric epithelial barrier.%紧密连接是血脑屏障及肠上皮屏障的结构和分子基础,其结构和功能改变是多种病原微生物从细胞旁路侵入机体的先决条件.此文分别就病原微生物如何调节血脑屏障及肠上皮屏障紧密连接结构,进而调节其功能方面的研究进展作一综述.

  6. TGF-β1 induced epithelial to mesenchymal transition (EMT in human bronchial epithelial cells is enhanced by IL-1β but not abrogated by corticosteroids

    Directory of Open Access Journals (Sweden)

    Zuraw Bruce L

    2009-10-01

    Full Text Available Abstract Background Chronic persistent asthma is characterized by ongoing airway inflammation and airway remodeling. The processes leading to airway remodeling are poorly understood, and there is increasing evidence that even aggressive anti-inflammatory therapy does not completely prevent this process. We sought to investigate whether TGFβ1 stimulates bronchial epithelial cells to undergo transition to a mesenchymal phenotype, and whether this transition can be abrogated by corticosteroid treatment or enhanced by the pro-inflammatory cytokine IL-1β. Methods BEAS-2B and primary normal human bronchial epithelial cells were stimulated with TGFβ1 and expression of epithelial and mesenchymal markers assessed by quantitative real-time PCR, immunoblotting, immunofluorescence microscopy and zymography. In some cases the epithelial cells were also incubated with corticosteroids or IL-1β. Results were analyzed using non-parametric statistical tests. Results Treatment of BEAS-2B or primary human bronchial epithelial cells with TGFβ1 significantly reduced the expression level of the epithelial adherence junction protein E-cadherin. TGFβ1 then markedly induced mesenchymal marker proteins such as collagen I, tenascin C, fibronectin and α-smooth muscle actin mRNA in a dose dependant manner. The process of mesenchymal transition was accompanied by a morphological change towards a more spindle shaped fibroblast cell type with a more motile and invasive phenotype. Corticosteroid pre-treatment did not significantly alter the TGFβ1 induced transition but IL-1β enhanced the transition. Conclusion Our results indicate, that TGFβ1 can induce mesenchymal transition in the bronchial epithelial cell line and primary cells. Since asthma has been strongly associated with increased expression of TGFβ1 in the airway, epithelial to mesenchymal transition may contribute to the contractile and fibrotic remodeling process that accompanies chronic asthma.

  7. Significance of myofibroblasts in oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Thode, Christenze; Jørgensen, Trine G.; Dabelsteen, Erik;

    2011-01-01

    -smooth muscle actin-positive myofibroblast that often represent the majority of tumor stromal cells. Their production of growth factors chemokines and extracellular matrix facilitates tumor growth. Myofibroblast have been demonstrated in close to 50% of oral squamous cell carcinomas. In this review, we...... highlight the histological distribution of myofibroblast in oral squamous cell and the myofibroblast relation to tumor growth on prognosis....

  8. PRL-3 expression in nasal sinus squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zi-Hui Chen; Min-Ying Li

    2016-01-01

    Objective:To investigate the relationship between liver regeneration phosphatase-3 (PRL-3) with differentiation extent of nasal sinus squamous cell carcinoma, and molecular biological effects on the pathogenesis of nasal sinus squamous cell carcinoma to comprehend its relevance, so as to make early diagnosis of patients, and to give guidance to the prognosis. Methods:Immunohistochemistry was used to detect PRL-3 in 30 cases of different degrees of sinus nasal squamous cell carcinoma. 20 cases of normal nasal cavity of mucosa tissues were set as control. Results:The PRL-3 in all levels of sinonasal squamous cell carcinoma tissues, there was a significant difference compared with the normal nasal mucosa (P<0.05), squamous cell carcinoma and its expression increased with the grade with enhanced trend. Conclusions:PRL-3 expression increased significantly in sinonasal squamous cell carcinoma than in nasal polyp tissue, showed that it may be associated with squamous cell carcinoma of nasal sinus squamous cell carcinoma, may be the early event.

  9. "Intercellular bridges" in a case of well differentiated squamous carcinoma.

    Science.gov (United States)

    Nguyen, Michaela; Mikita, Geoffrey; Hoda, Rana S

    2016-02-01

    Intercellular bridges may aide in definitive identification of malignant cell origin, especially in squamous cell carcinoma. They are difficult to identify in routine cytologic specimens and are especially rare in smear preparations. Herein, we present images of intercellular bridges from a case of well differentiated squamous cell carcinoma of the esophagus in a cytologic specimen obtained from FNA of a paraesophageal lymph node.

  10. Comprehensive genomic characterization of squamous cell lung cancers

    NARCIS (Netherlands)

    Hammerman, Peter S.; Lawrence, Michael S.; Voet, Douglas; Jing, Rui; Cibulskis, Kristian; Sivachenko, Andrey; Stojanov, Petar; McKenna, Aaron; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Sougnez, Carrie; Imielinski, Marcin; Helman, Elena; Hernandez, Bryan; Pho, Nam H.; Meyerson, Matthew; Chu, Andy; Chun, Hye-Jung E.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Sipahimalani, Payal; Stoll, Dominik; Balasundaram, Miruna; Birol, Inanc; Butterfield, Yaron S. N.; Chuah, Eric; Coope, Robin J. N.; Corbett, Richard; Dhalla, Noreen; Guin, Ranabir; Hirst, Anhe Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Karen; Nip, Ka Ming; Olshen, Adam; Schein, Jacqueline E.; Slobodan, Jared R.; Tam, Angela; Thiessen, Nina; Varhol, Richard; Zeng, Thomas; Zhao, Yongjun; Jones, Steven J. M.; Marra, Marco A.; Saksena, Gordon; Cherniack, Andrew D.; Schumacher, Stephen E.; Tabak, Barbara; Carter, Scott L.; Pho, Nam H.; Nguyen, Huy; Onofrio, Robert C.; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Hammerman, Peter S.; Getz, Gad; Meyerson, Matthew; Protopopov, Alexei; Zhang, Jianhua; Hadjipanayis, Angela; Lee, Semin; Xi, Ruibin; Yang, Lixing; Ren, Xiaojia; Zhang, Hailei; Shukla, Sachet; Chen, Peng-Chieh; Haseley, Psalm; Lee, Eunjung; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Socci, Nicholas D.; Liang, Yupu; Schultz, Nikolaus; Borsu, Laetitia; Lash, Alex E.; Viale, Agnes; Sander, Chris; Ladanyi, Marc; Auman, J. Todd; Hoadley, Katherine A.; Wilkerson, Matthew D.; Shi, Yan; Liquori, Christina; Meng, Shaowu; Li, Ling; Turman, Yidi J.; Topal, Michael D.; Tan, Donghui; Waring, Scot; Buda, Elizabeth; Walsh, Jesse; Jones, Corbin D.; Mieczkowski, Piotr A.; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Dolina, Peter; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; O'Connor, Brian D.; Prins, Jan F.; Liu, Jinze; Chiang, Derek Y.; Hayes, D. Neil; Perou, Charles M.; Cope, Leslie; Danilova, Ludmila; Weisenberger, Daniel J.; Maglinte, Dennis T.; Pan, Fei; Van den Berg, David J.; Triche, Timothy; Herman, James G.; Baylin, Stephen B.; Laird, Peter W.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Jinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Schultz, Nikolaus; Sinha, Rileen; Ciriello, Giovanni; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Gao, Jianjiong; Aksoy, B. Arman; Weinhold, Nils; Ramirez, Ricardo; Taylor, Barry S.; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Mo, Qianxing; Seshan, Venkatraman; Paik, Paul K.; Ladanyi, Marc; Sander, Chris; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod; Unruh, Anna; Wakefield, Chris; Cason, R. Craig; Baggerly, Keith A.; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Zhu, Jingchun; Szeto, Christopher; Scott, Gary K.; Yau, Christina; Ng, Sam; Goldstein, Ted; Waltman, Peter; Sokolov, Artem; Ellrott, Kyle; Collisson, Eric A.; Zerbino, Daniel; Wilks, Christopher; Ma, Singer; Craft, Brian; Wilkerson, Matthew D.; Auman, J. Todd; Hoadley, Katherine A.; Du, Ying; Cabanski, Christopher; Walter, Vonn; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Marron, J. S.; Liu, Yufeng; Wang, Kai; Liu, Jinze; Prins, Jan F.; Hayes, D. Neil; Perou, Charles M.; Creighton, Chad J.; Zhang, Yiqun; Travis, William D.; Rekhtman, Natasha; Yi, Joanne; Aubry, Marie C.; Cheney, Richard; Dacic, Sanja; Flieder, Douglas; Funkhouser, William; Illei, Peter; Myers, Jerome; Tsao, Ming-Sound; Penny, Robert; Mallery, David; Shelton, Troy; Hatfield, Martha; Morris, Scott; Yena, Peggy; Shelton, Candace; Sherman, Mark; Paulauskis, Joseph; Meyerson, Matthew; Baylin, Stephen B.; Govindan, Ramaswamy; Akbani, Rehan; Azodo, Ijeoma; Beer, David; Bose, Ron; Byers, Lauren A.; Carbone, David; Chang, Li-Wei; Chiang, Derek; Chu, Andy; Chun, Elizabeth; Collisson, Eric; Cope, Leslie; Creighton, Chad J.; Danilova, Ludmila; Ding, Li; Getz, Gad; Hammerman, Peter S.; Hayes, D. Neil; Hernandez, Bryan; Herman, James G.; Heymach, John; Ida, Cristiane; Imielinski, Marcin; Johnson, Bruce; Jurisica, Igor; Kaufman, Jacob; Kosari, Farhad; Kucherlapati, Raju; Kwiatkowski, David; Ladanyi, Marc; Lawrence, Michael S.; Maher, Christopher A.; Mungall, Andy; Ng, Sam; Pao, William; Peifer, Martin; Penny, Robert; Robertson, Gordon; Rusch, Valerie; Sander, Chris; Schultz, Nikolaus; Shen, Ronglai; Siegfried, Jill; Sinha, Rileen; Sivachenko, Andrey; Sougnez, Carrie; Stoll, Dominik; Stuart, Joshua; Thomas, Roman K.; Tomaszek, Sandra; Tsao, Ming-Sound; Travis, William D.; Vaske, Charles; Weinstein, John N.; Weisenberger, Daniel; Wheeler, David; Wigle, Dennis A.; Wilkerson, Matthew D.; Wilks, Christopher; Yang, Ping; Zhang, Jianjua John; Jensen, Mark A.; Sfeir, Robert; Kahn, Ari B.; Chu, Anna L.; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric E.; Pontius, Joan; Pihl, Todd D.; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique L.; Nicholls, Matthew C.; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter A.; Alonso, Shelley; Sanbhadti, Rashmi N.; Barletta, Sean P.; Greene, John M.; Pot, David A.; Tsao, Ming-Sound; Bandarchi-Chamkhaleh, Bizhan; Boyd, Jeff; Weaver, JoEllen; Wigle, Dennis A.; Azodo, Ijeoma A.; Tomaszek, Sandra C.; Aubry, Marie Christine; Ida, Christiane M.; Yang, Ping; Kosari, Farhad; Brock, Malcolm V.; Rogers, Kristen; Rutledge, Marian; Brown, Travis; Lee, Beverly; Shin, James; Trusty, Dante; Dhir, Rajiv; Siegfried, Jill M.; Potapova, Olga; Fedosenko, Konstantin V.; Nemirovich-Danchenko, Elena; Rusch, Valerie; Zakowski, Maureen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Fan, Zhen; Todaro, Nicole; Eckman, John; Myers, Jerome; Rathmell, W. Kimryn; Thorne, Leigh B.; Huang, Mei; Boice, Lori; Hill, Ashley; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Morrison, Carl; Gaudioso, Carmelo; Bartlett, Johnm. S.; Kodeeswaran, Sugy; Zanke, Brent; Sekhon, Harman; David, Kerstin; Juhl, Hartmut; Van Le, Xuan; Kohl, Bernard; Thorp, Richard; Tien, Nguyen Viet; Van Bang, Nguyen; Sussman, Howard; Phu, Bui Duc; Hajek, Richard; PhiHung, Nguyen; Khan, Khurram Z.; Muley, Thomas; Shaw, Kenna R. Mills; Sheth, Margi; Yang, Liming; Buetow, Ken; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin; Dillon, Laura A. L.; Schaefer, Carl; Guyer, Mark S.; Ozenberger, Bradley A.; Palchik, Jacqueline D.; Peterson, Jane; Sofia, Heidi J.; Thomson, Elizabeth; Meyerson, Matthew

    2012-01-01

    Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment.

  11. Comprehensive genomic characterization of squamous cell lung cancers

    NARCIS (Netherlands)

    Hammerman, Peter S.; Lawrence, Michael S.; Voet, Douglas; Jing, Rui; Cibulskis, Kristian; Sivachenko, Andrey; Stojanov, Petar; McKenna, Aaron; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Sougnez, Carrie; Imielinski, Marcin; Helman, Elena; Hernandez, Bryan; Pho, Nam H.; Meyerson, Matthew; Chu, Andy; Chun, Hye-Jung E.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Sipahimalani, Payal; Stoll, Dominik; Balasundaram, Miruna; Birol, Inanc; Butterfield, Yaron S. N.; Chuah, Eric; Coope, Robin J. N.; Corbett, Richard; Dhalla, Noreen; Guin, Ranabir; Hirst, Anhe Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Karen; Nip, Ka Ming; Olshen, Adam; Schein, Jacqueline E.; Slobodan, Jared R.; Tam, Angela; Thiessen, Nina; Varhol, Richard; Zeng, Thomas; Zhao, Yongjun; Jones, Steven J. M.; Marra, Marco A.; Saksena, Gordon; Cherniack, Andrew D.; Schumacher, Stephen E.; Tabak, Barbara; Carter, Scott L.; Pho, Nam H.; Nguyen, Huy; Onofrio, Robert C.; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Hammerman, Peter S.; Getz, Gad; Meyerson, Matthew; Protopopov, Alexei; Zhang, Jianhua; Hadjipanayis, Angela; Lee, Semin; Xi, Ruibin; Yang, Lixing; Ren, Xiaojia; Zhang, Hailei; Shukla, Sachet; Chen, Peng-Chieh; Haseley, Psalm; Lee, Eunjung; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Socci, Nicholas D.; Liang, Yupu; Schultz, Nikolaus; Borsu, Laetitia; Lash, Alex E.; Viale, Agnes; Sander, Chris; Ladanyi, Marc; Auman, J. Todd; Hoadley, Katherine A.; Wilkerson, Matthew D.; Shi, Yan; Liquori, Christina; Meng, Shaowu; Li, Ling; Turman, Yidi J.; Topal, Michael D.; Tan, Donghui; Waring, Scot; Buda, Elizabeth; Walsh, Jesse; Jones, Corbin D.; Mieczkowski, Piotr A.; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Dolina, Peter; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; O'Connor, Brian D.; Prins, Jan F.; Liu, Jinze; Chiang, Derek Y.; Hayes, D. Neil; Perou, Charles M.; Cope, Leslie; Danilova, Ludmila; Weisenberger, Daniel J.; Maglinte, Dennis T.; Pan, Fei; Van den Berg, David J.; Triche, Timothy; Herman, James G.; Baylin, Stephen B.; Laird, Peter W.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Jinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Schultz, Nikolaus; Sinha, Rileen; Ciriello, Giovanni; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Gao, Jianjiong; Aksoy, B. Arman; Weinhold, Nils; Ramirez, Ricardo; Taylor, Barry S.; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Mo, Qianxing; Seshan, Venkatraman; Paik, Paul K.; Ladanyi, Marc; Sander, Chris; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod; Unruh, Anna; Wakefield, Chris; Cason, R. Craig; Baggerly, Keith A.; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Zhu, Jingchun; Szeto, Christopher; Scott, Gary K.; Yau, Christina; Ng, Sam; Goldstein, Ted; Waltman, Peter; Sokolov, Artem; Ellrott, Kyle; Collisson, Eric A.; Zerbino, Daniel; Wilks, Christopher; Ma, Singer; Craft, Brian; Wilkerson, Matthew D.; Auman, J. Todd; Hoadley, Katherine A.; Du, Ying; Cabanski, Christopher; Walter, Vonn; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Marron, J. S.; Liu, Yufeng; Wang, Kai; Liu, Jinze; Prins, Jan F.; Hayes, D. Neil; Perou, Charles M.; Creighton, Chad J.; Zhang, Yiqun; Travis, William D.; Rekhtman, Natasha; Yi, Joanne; Aubry, Marie C.; Cheney, Richard; Dacic, Sanja; Flieder, Douglas; Funkhouser, William; Illei, Peter; Myers, Jerome; Tsao, Ming-Sound; Penny, Robert; Mallery, David; Shelton, Troy; Hatfield, Martha; Morris, Scott; Yena, Peggy; Shelton, Candace; Sherman, Mark; Paulauskis, Joseph; Meyerson, Matthew; Baylin, Stephen B.; Govindan, Ramaswamy; Akbani, Rehan; Azodo, Ijeoma; Beer, David; Bose, Ron; Byers, Lauren A.; Carbone, David; Chang, Li-Wei; Chiang, Derek; Chu, Andy; Chun, Elizabeth; Collisson, Eric; Cope, Leslie; Creighton, Chad J.; Danilova, Ludmila; Ding, Li; Getz, Gad; Hammerman, Peter S.; Hayes, D. Neil; Hernandez, Bryan; Herman, James G.; Heymach, John; Ida, Cristiane; Imielinski, Marcin; Johnson, Bruce; Jurisica, Igor; Kaufman, Jacob; Kosari, Farhad; Kucherlapati, Raju; Kwiatkowski, David; Ladanyi, Marc; Lawrence, Michael S.; Maher, Christopher A.; Mungall, Andy; Ng, Sam; Pao, William; Peifer, Martin; Penny, Robert; Robertson, Gordon; Rusch, Valerie; Sander, Chris; Schultz, Nikolaus; Shen, Ronglai; Siegfried, Jill; Sinha, Rileen; Sivachenko, Andrey; Sougnez, Carrie; Stoll, Dominik; Stuart, Joshua; Thomas, Roman K.; Tomaszek, Sandra; Tsao, Ming-Sound; Travis, William D.; Vaske, Charles; Weinstein, John N.; Weisenberger, Daniel; Wheeler, David; Wigle, Dennis A.; Wilkerson, Matthew D.; Wilks, Christopher; Yang, Ping; Zhang, Jianjua John; Jensen, Mark A.; Sfeir, Robert; Kahn, Ari B.; Chu, Anna L.; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric E.; Pontius, Joan; Pihl, Todd D.; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique L.; Nicholls, Matthew C.; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter A.; Alonso, Shelley; Sanbhadti, Rashmi N.; Barletta, Sean P.; Greene, John M.; Pot, David A.; Tsao, Ming-Sound; Bandarchi-Chamkhaleh, Bizhan; Boyd, Jeff; Weaver, JoEllen; Wigle, Dennis A.; Azodo, Ijeoma A.; Tomaszek, Sandra C.; Aubry, Marie Christine; Ida, Christiane M.; Yang, Ping; Kosari, Farhad; Brock, Malcolm V.; Rogers, Kristen; Rutledge, Marian; Brown, Travis; Lee, Beverly; Shin, James; Trusty, Dante; Dhir, Rajiv; Siegfried, Jill M.; Potapova, Olga; Fedosenko, Konstantin V.; Nemirovich-Danchenko, Elena; Rusch, Valerie; Zakowski, Maureen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Fan, Zhen; Todaro, Nicole; Eckman, John; Myers, Jerome; Rathmell, W. Kimryn; Thorne, Leigh B.; Huang, Mei; Boice, Lori; Hill, Ashley; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Morrison, Carl; Gaudioso, Carmelo; Bartlett, Johnm. S.; Kodeeswaran, Sugy; Zanke, Brent; Sekhon, Harman; David, Kerstin; Juhl, Hartmut; Van Le, Xuan; Kohl, Bernard; Thorp, Richard; Tien, Nguyen Viet; Van Bang, Nguyen; Sussman, Howard; Phu, Bui Duc; Hajek, Richard; PhiHung, Nguyen; Khan, Khurram Z.; Muley, Thomas; Shaw, Kenna R. Mills; Sheth, Margi; Yang, Liming; Buetow, Ken; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin; Dillon, Laura A. L.; Schaefer, Carl; Guyer, Mark S.; Ozenberger, Bradley A.; Palchik, Jacqueline D.; Peterson, Jane; Sofia, Heidi J.; Thomson, Elizabeth; Meyerson, Matthew

    2012-01-01

    Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment.

  12. Squamous Cell Carcinoma of the Oral Cavity in the Elderly

    Directory of Open Access Journals (Sweden)

    Yi-Shing Leu

    2009-03-01

    Conclusion: Squamous cell carcinoma of the oral cavity did not have a significantly different outcome for elderly patients when compared with younger patients. Elderly patients with stage IVA squamous cell carcinoma of the oral cavity had poorer survival rates. When properly evaluated and monitored, conservative and conventional therapies seemed efficacious in the elderly.

  13. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  14. Hydraulic fracture during epithelial stretching

    Science.gov (United States)

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

  15. Ixabepilone in Treating Patients With Metastatic or Recurrent Squamous Cell Cancer of the Head and Neck

    Science.gov (United States)

    2013-02-26

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  16. ADAMTS-10 and -6 differentially regulate cell-cell junctions and focal adhesions

    Science.gov (United States)

    Cain, Stuart A.; Mularczyk, Ewa J.; Singh, Mukti; Massam-Wu, Teresa; Kielty, Cay M.

    2016-01-01

    ADAMTS10 and ADAMTS6 are homologous metalloproteinases with ill-defined roles. ADAMTS10 mutations cause Weill-Marchesani syndrome (WMS), implicating it in fibrillin microfibril biology since some fibrillin-1 mutations also cause WMS. However little is known about ADAMTS6 function. ADAMTS10 is resistant to furin cleavage, however we show that ADAMTS6 is effectively processed and active. Using siRNA, over-expression and mutagenesis, it was found ADAMTS6 inhibits and ADAMTS10 is required for focal adhesions, epithelial cell-cell junction formation, and microfibril deposition. Either knockdown of ADAMTS6, or disruption of its furin processing or catalytic sites restores focal adhesions, implicating its enzyme activity acts on targets in the focal adhesion complex. In ADAMTS10-depleted cultures, expression of syndecan-4 rescues focal adhesions and cell-cell junctions. Recombinant C-termini of ADAMTS10 and ADAMTS6, both of which induce focal adhesions, bind heparin and syndecan-4. However, cells overexpressing full-length ADAMTS6 lack heparan sulphate and focal adhesions, whilst depletion of ADAMTS6 induces a prominent glycocalyx. Thus ADAMTS10 and ADAMTS6 oppositely affect heparan sulphate-rich interfaces including focal adhesions. We previously showed that microfibril deposition requires fibronectin-induced focal adhesions, and cell-cell junctions in epithelial cultures. Here we reveal that ADAMTS6 causes a reduction in heparan sulphate-rich interfaces, and its expression is regulated by ADAMTS10. PMID:27779234

  17. Physics and Applications of NIS Junctions

    Energy Technology Data Exchange (ETDEWEB)

    Ullom, J N

    2001-08-24

    This paper reviews the physics and applications of Normal-Insulator-Superconductor (NIS) tunnel junctions. The current-voltage properties of NIS junctions are diode-like with a strong temperature dependence. Hence, these structures can be used as sensitive thermometers at temperatures well below the energy gap, {Delta}, of the superconducting electrode. For junction voltages comparable to {Delta}/q, current flow removes energy from the normal electrode. This property has been exploited to build refrigerators capable of cooling thin-film circuits from 0.3 K to 0.1 K. Calorimeters and bolometers for the detection of X-rays and millimeter-wave radiation, respectively, have successfully been built from NIS junctions. NIS junctions have also been used to probe the superconducting state. Finally, recent ideas for the use of NIS junctions as simple circuit elements are described.

  18. Algorithms for Junctions in Directed Acyclic Graphs

    CERN Document Server

    Ferreira, Carlos Eduardo

    2012-01-01

    Given a pair of distinct vertices u, v in a graph G, we say that s is a junction of u, v if there are in G internally vertex disjoint directed paths from s to u and from s to v. We show how to characterize junctions in directed acyclic graphs. We also consider the two problems in the following and derive efficient algorithms to solve them. Given a directed acyclic graph G and a vertex s in G, how can we find all pairs of vertices of G such that s is a junction of them? And given a directed acyclic graph G and k pairs of vertices of G, how can we preprocess G such that all junctions of k given pairs of vertices could be listed quickly? All junctions of k pairs problem arises in an application in Anthropology and we apply our algorithm to find such junctions on kinship networks of some brazilian indian ethnic groups.

  19. Management of tonsillar squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴雪溪; 唐平章; 祁永发; 徐震纲

    2003-01-01

    Objective To discuss treatment options for tonsillar squamous cell carcinoma.Methods A total of 108 patients with biopsy-proven tonsillar squamous cell carcinoma, treated between 1984 and 2000, were reviewed, including 82 men and 26 women, with ages ranging from 19 to 70 years. Treatments consisted of either radiotherapy and surgery reserved as salvage treatment (Salvage Surgery, 83 patients), or planned surgery with preoperative radiation (Planned Surgery, 25 patients). Radiotherapy was delivered primarily in a dosage of 60-70 Gy for Salvage Surgery patients and 40-50 Gy for Planned Surgery patients. Both salvage and planned surgeries were radical, with resection of the lateral oropharyngeal wall, segmental resection of the mandible and neck dissection. The pectoralis major myocutaneous flaps were used to repair surgical defects. Results The percentages of radical surgery used in the Salvage Surgery and Planned Surgery groups were 24.1% (20/83) and 88.0% (22/25), respectively (P=0.000). The local recurrence rates were 28.9% (24/83) and 20.0% (5/25) in the Salvage Surgery and Planned Surgery groups, respectively (P= 0.378). The neck recurrence rates were 9.6% (8/83) and 8.0% (2/25) in the Salvage Surgery and Planned Surgery groups respeatively (P= 0.804). The 5-year survival rates were 59.3% and 55.3% in the Salvage Surgery and Planned Surgery groups, respeatively (P= 0.7056).Conclusions Although the two treatments had a similar survival rate, Salvage Surgery avoided 60% commando operations compared with the Planned Surgery group, which benefits to recovery of oral functions. Primary radiotherapy is recommended as the treatment of choice for tonsillar squamous cell carcinoma. After radical radiotherapy, salvage surgery should be undertaken in the case of tumor remnants or recurrences.

  20. Molecular junctions: can pulling influence optical controllability?

    Science.gov (United States)

    Parker, Shane M; Smeu, Manuel; Franco, Ignacio; Ratner, Mark A; Seideman, Tamar

    2014-08-13

    We suggest the combination of single molecule pulling and optical control as a way to enhance control over the electron transport characteristics of a molecular junction. We demonstrate using a model junction consisting of biphenyl-dithiol coupled to gold contacts. The junction is pulled while optically manipulating the dihedral angle between the two rings. Quantum dynamics simulations show that molecular pulling enhances the degree of control over the dihedral angle and hence over the transport properties.

  1. Extensive focal epithelial hyperplasia.

    Science.gov (United States)

    Hashemipour, Maryam Alsadat; Shoryabi, Ali; Adhami, Shahrzad; Mehrabizadeh Honarmand, Hoda

    2010-01-01

    Heck's disease or focal epithelial hyperplasia is a benign contagious disease caused by human papillomavirus types 13 or 32. It occurs with low frequency in the Iranian population. This condition is characterized by the occurrence of multiple, small papules or nodules in the oral cavity, especially on the labial and buccal mucosa and tongue. In some populations, up to 39% of children are affected. Conservative surgical excision of lesions may be performed for diagnostic or aesthetic purposes. The risk of recurrence after this therapy is minimal, and there seems to be no malignant transformation potential. In the present work, we presented the clinical case of a 12-year-old Iranian girl with oral lesions that clinically and histologically correspond to Heck's disease.

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

    Science.gov (United States)

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

    2009-02-01

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

  3. The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.

    Directory of Open Access Journals (Sweden)

    Gu-Qing Zeng

    Full Text Available BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1 was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(apyrene (B[a]P-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.

  4. Loss models for long Josephson junctions

    DEFF Research Database (Denmark)

    Olsen, O. H.; Samuelsen, Mogens Rugholm

    1984-01-01

    A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement.......A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement....

  5. PATIENTS WITH SQUAMOUS-CELL VERSUS ADENO(SQUAMOUS) CARCINOMA OF THE CERVIX, WHAT FACTORS DETERMINE THE PROGNOSIS

    NARCIS (Netherlands)

    TINGA, DJ; BOUMA, J; AALDERS, JG

    1992-01-01

    Patients with squamous cell carcinoma of the cervix FIGO stages IB to IV (n = 306) were compared to patients with adeno(squamous) carcinoma (n = 70). There was no difference between the mean ages of the groups. In the patients who underwent radical surgical treatment, whether or not in combination w

  6. Pre-operative sequential chemo- and radiochemotherapy in locally advanced carcinomas of the lower oesophagus and gastro-oesophageal junction

    Energy Technology Data Exchange (ETDEWEB)

    Wilke, H.; Mueller, C. [Department of Internal Medicine (Cancer Research), Essen University Medical School, D-45 122 Essen (Germany); Walz, M.K. [Department of General Surgery, Essen University Medical School, D-45 122 Essen (Germany); Stuschke, M. [Department of Radiotherapy, Essen University Medical School, D-45 122 Essen (Germany); Vanhoefer, U.; Stahl, M. [Department of Internal Medicine (Cancer Research), Essen University Medical School, D-45 122 Essen (Germany)

    1998-04-01

    The purpose of this trial was to examine the feasibility of intensive, sequential chemo- and radiochemotherapy followed by surgery in patients with locally advanced carcinomas of the lower oesophagus and the gastro-oesophageal junction (GO junction). The chemotherapy consisted of two courses of 6 weekly administrations of 5-fluorouracil (5-FU) (2.0 g/m{sup 2}, 24 h infusion) and folinic acid (FA) (500 mg/m{sup 2}, 2 h infusion) combined with twice weekly cisplatin (50 mg/m{sup 2}, 1 h infusion). Irradiation of 30 Gy was given concurrently with one course of cisplatin and etoposide. 25 patients with locally advanced (T3-T4 NX M0) squamous cell or adenocarcinoma of the lower oesophagus and GO junction were included and evaluated. Toxicity was usually mild to moderate (WHO grade 1 and 2) with mucositis as the most important side-effect of the pre-operative treatment. Of the patients, 94 and 88% completed the chemo- and radiochemotherapy according to the protocol, respectively. A major response (=partial remission with subjective improvement) to chemotherapy was achieved in 6/10 patients with squamous cell carcinoma and 10/15 with adenocarcinoma. 19 patients had subsequent surgery and complete resection was achieved in 16 (3 patients had intra-abdominal metastases observed at laparotomy). The operative mortality rate was 16% (3/19). 10 of the 16 patients with tumour resection had a pathological complete response. 15 patients (43%) remain alive at a median follow-up of 20 months and the median survival exceeds 16+ months. Our data suggest that this intensive pre-operative chemoradiotherapy programme is feasible and remarkably effective in patients with locally advanced carcinomas of the lower oesophagus or GO junction. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  7. Etk/Bmx activation modulates barrier function in epithelial cells.

    Science.gov (United States)

    Hamm-Alvarez, S F; Chang, A; Wang, Y; Jerdeva, G; Lin, H H; Kim, K J; Ann, D K

    2001-06-01

    Etk/Bmx is a member of the Tec family of cytoplasmic non-receptor tyrosine kinases known to express in epithelial cells. We demonstrate herein that Etk activation in stably Etk-transfected epithelial Pa-4 cells resulted in a consistently increased transepithelial resistance (TER). After 24 h of hypoxic (1% O(2)) exposure, the TER and equivalent active ion transport rate (I(eq)) were reduced to <5% of the normoxia control in Pa-4 cells, whereas both TER and I(eq) were maintained at comparable and 60% levels, respectively, relative to their normoxic controls in cells with Etk activation. Moreover, Pa-4 cells exhibited an abundant actin stress fiber network with a diffuse distribution of beta-catenin at the cell periphery. By contrast, Etk-activated cells displayed a redistribution of actin to an exclusively peripheral network, with a discrete band of beta-catenin also concentrated at the cell periphery, and an altered occludin distribution profile. On the basis of these findings, we propose that Etk may be a novel regulator of epithelial junctions during physiological and pathophysiological conditions.

  8. Paracellular epithelial sodium transport maximizes energy efficiency in the kidney.

    Science.gov (United States)

    Pei, Lei; Solis, Glenn; Nguyen, Mien T X; Kamat, Nikhil; Magenheimer, Lynn; Zhuo, Min; Li, Jiahua; Curry, Joshua; McDonough, Alicia A; Fields, Timothy A; Welch, William J; Yu, Alan S L

    2016-07-01

    Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney. We found that claudin-2-null mice conserve sodium to the same extent as WT mice, even during profound dietary sodium depletion, as a result of the upregulation of transcellular Na-K-2Cl transport activity in the thick ascending limb of Henle. We hypothesized that shifting sodium transport to transcellular pathways would lead to increased whole-kidney oxygen consumption. Indeed, compared with control animals, oxygen consumption in the kidneys of claudin-2-null mice was markedly increased, resulting in medullary hypoxia. Furthermore, tubular injury in kidneys subjected to bilateral renal ischemia-reperfusion injury was more severe in the absence of claudin-2. Our results indicate that paracellular transport in the PT is required for efficient utilization of oxygen in the service of sodium transport. We speculate that paracellular permeability may have evolved as a general strategy in epithelial tissues to maximize energy efficiency.

  9. Expression of Connexin43 in Rat Epithelial Cells and Fibroblasts

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To explore the role of connexin43 (Cx43) in gap junctional intercellular communication (GJIC) and propagated sensation along meridians, the expression of Cx43 in the rat epithelial cells and fibroblasts was studied both in vitro and in vivo. With the in vitro study, the rat epithelial cells and fibroblasts were cultured together, and the localization of Cx43 was detected by immunohistochemistry and indirect immunofluorescent cytochemistry and under confocal microscopy . And the expression of Cx43 on the surface of the cells was examined by flow cytometry. With the in vivo examination, 20 SD rats were randomized into control group (n = 10) and electrical acupuncture group (EAgroup, n=10). EA ( 0.5-1.5 V, 4-16 Hz , 30 min) was applied to"Zusanli"acupoint for 30 min at rat's hind paw, the localization of Cx43 was immunohistochemically detected.The immunohistochemical staining and indirect immunfluorescent cytochemistry showed that Cx43was localized on the surface of the cells and in the cytoplasm. The relative expression level of Cx43on the cellular membrane surfaces of the rat epithelial cells and fibroblasts, as determined by FACS, were 13.91 % and 29.53 % respectively. Our studied suggested that Cx43 might be involved in GJIC and propagated sensation along meridians.

  10. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions

    OpenAIRE

    1994-01-01

    Occludin is an integral membrane protein localizing at tight junctions (TJ) with four transmembrane domains and a long COOH-terminal cytoplasmic domain (domain E) consisting of 255 amino acids. Immunofluorescence and laser scan microscopy revealed that chick full- length occludin introduced into human and bovine epithelial cells was correctly delivered to and incorporated into preexisting TJ. Further transfection studies with various deletion mutants showed that the domain E, especially its C...

  11. HIV infection induces morphometrical changes on the oral (buccal mucosa and tongue) epithelial cells.

    Science.gov (United States)

    Pompermayer, Adriane Bastos; Gil, Francisca Berenice Dias; França, Beatriz Helena Sottile; Machado, Maria Ângela Naval; Trevilatto, Paula Cristina; Fernandes, Angela; de Lima, Antônio Adilson Soares

    2011-01-01

    The aim of this study was to assess morphological and morphometrical alterations of oral squamous epithelial cells in type 1 HIV infected individuals. Oral smears were collected from tongue and buccal mucosa of 30 HIV infected (experimental) and 30 non-infected (control) individuals by liquid-based exfoliative cytology. The cells were morphologically analyzed and the nuclear area (NA), the cytoplasmic area (CA) and the nucleus-to-cytoplasm area ratio (NA/CA) were calculated. No morphological differences were found between the groups. The mean values of CA were decreased in tongue (P=.00006) and buccal mucosa (P=.00242) in HIV infected individual, while mean values of NA were increased (P=.00308 and .00095, respectively) in the same group. NA/CA ratio for experimental group was increased in both collected places, with P=.00001 (tongue) and P=.00000 (buccal mucosa). This study revealed that HIV infection was able to induce morphometrical changes on the oral epithelial cells.

  12. Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness.

    Science.gov (United States)

    Kikuchi, T; Adams, J C; Miyabe, Y; So, E; Kobayashi, T

    2000-01-01

    In the mammalian cochlea, there are two independent gap junction systems, the epithelial cell gap junction system and the connective tissue cell gap junction system. Thus far, four different connexin molecules, including connexin 26, 30, 31, and 43, have been reported in the cochlea. The two networks of gap junctions form the route by which K+ ions that pass through the sensory cells during mechanosensory transduction can be recycled back to the endolymphatic space, from which they reenter the sensory cells. Activation of hair cells by acoustic stimuli induces influx of K+ ions from the endolymph to sensory hair cells. These K+ ions are released basolaterally to the extracellular space of the organ of Corti, from which they enter the cochlear supporting cells. Once inside the supporting cells they move via the epithelial cell gap junction system laterally to the lower part of the spiral ligament. The K+ ions are released into the extracellular space of the spiral ligament by root cells and taken up by type II fibrocytes. This uptake incorporates K+ into the connective tissue gap junction system. Within this system, the K+ ions pass through the tight junctional barrier of the stria vascularis and are released within the intrastrial extracellular space. The marginal cells of the stria vascularis then take up K+ and return it to the endolymphatic space, where it can be used again in sensory transduction. It is highly probable that mutations of connexin genes that result in human nonsyndromic deafness cause dysfunction of cochlear gap junctions and thereby interrupt K+ ion recirculation pathways. In addition to connexin mutations, other conditions may disrupt gap junctions within the ear. For example, mice with a functionally significant mutation of Brain-4, which is expressed in the connective tissue cells within the cochlea, show marked depression of the endolymphatic potential and profound sensorineural hearing loss. It seems likely that disruption of connective

  13. Selective functionalization of nanofiber scaffolds to regulate salivary gland epithelial cell proliferation and polarity.

    Science.gov (United States)

    Cantara, Shraddha I; Soscia, David A; Sequeira, Sharon J; Jean-Gilles, Riffard P; Castracane, James; Larsen, Melinda

    2012-11-01

    Epithelial cell types typically lose apicobasal polarity when cultured on 2D substrates, but apicobasal polarity is required for directional secretion by secretory cells, such as salivary gland acinar cells. We cultured salivary gland epithelial cells on poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds that mimic the basement membrane, a specialized extracellular matrix, and examined cell proliferation and apicobasal polarization. Although cells proliferated on nanofibers, chitosan-coated nanofiber scaffolds stimulated proliferation of salivary gland epithelial cells. Although apicobasal cell polarity was promoted by the nanofiber scaffolds relative to flat surfaces, as determined by the apical localization of ZO-1, it was antagonized by the presence of chitosan. Neither salivary gland acinar nor ductal cells fully polarized on the nanofiber scaffolds, as determined by the homogenous membrane distribution of the mature tight junction marker, occludin. However, nanofiber scaffolds chemically functionalized with the basement membrane protein, laminin-111, promoted more mature tight junctions, as determined by apical localization of occludin, but did not affect cell proliferation. To emulate the multifunctional capabilities of the basement membrane, bifunctional PLGA nanofibers were generated. Both acinar and ductal cell lines responded to signals provided by bifunctional scaffolds coupled to chitosan and laminin-111, demonstrating the applicability of such scaffolds for epithelial cell types.

  14. Magnetofection Enhances Lentiviral-Mediated Transduction of Airway Epithelial Cells through Extracellular and Cellular Barriers.

    Science.gov (United States)

    Castellani, Stefano; Orlando, Clara; Carbone, Annalucia; Di Gioia, Sante; Conese, Massimo

    2016-11-23

    Gene transfer to airway epithelial cells is hampered by extracellular (mainly mucus) and cellular (tight junctions) barriers. Magnetofection has been used to increase retention time of lentiviral vectors (LV) on the cellular surface. In this study, magnetofection was investigated in airway epithelial cell models mimicking extracellular and cellular barriers. Bronchiolar epithelial cells (H441 line) were evaluated for LV-mediated transduction after polarization onto filters and dexamethasone (dex) treatment, which induced hemicyst formation, with or without magnetofection. Sputum from cystic fibrosis (CF) patients was overlaid onto cells, and LV-mediated transduction was evaluated in the absence or presence of magnetofection. Magnetofection of unpolarized H441 cells increased the transduction with 50 MOI (multiplicity of infection, i.e., transducing units/cell) up to the transduction obtained with 500 MOI in the absence of magnetofection. Magnetofection well-enhanced LV-mediated transduction in mucus-layered cells by 20.3-fold. LV-mediated transduction efficiency decreased in dex-induced hemicysts in a time-dependent fashion. In dome-forming cells, zonula occludens-1 (ZO-1) localization at the cell borders was increased by dex treatment. Under these experimental conditions, magnetofection significantly increased LV transduction by 5.3-fold. In conclusion, these results show that magnetofection can enhance LV-mediated gene transfer into airway epithelial cells in the presence of extracellular (sputum) and cellular (tight junctions) barriers, representing CF-like conditions.

  15. Use of impression cytology for the detection of unsuspected ocular surface squamous neoplasia cells in pterygia

    Directory of Open Access Journals (Sweden)

    Jeison de Nadai Barros

    2014-10-01

    Full Text Available Purpose: To evaluate the agreement between the methodologies of impression cytology (IC and histopathology regarding epithelial lesions clinically diagnosed as pterygium and also regarding the detection of unsuspected and associated ocular surface squamous neoplasia (OSSN. Methods: Thirty-two Brazilian patients were included and IC was performed on all pterygia before excision. Histopathogical examination was considered the gold standard and was performed by two experienced ocular pathologists in which consensus existed regarding pterygia diagnosis. IC accuracy was assessed by sensitivity and specificity with a 95% confidence interval. Results: From the 32 primary lesions studied, histopathological examination confirmed the diagnosis of pterygium without atypical cells in 19 cases (60% and showed unsuspected and associated OSSN cells in 13 cases (40%. IC demonstrated one false-negative and one false-positive result for atypia. Statistical analysis showed an estimated sensitivity of 92%, specificity of 94%, positive predictive value of 92%, and negative predictive value of 94%. Conclusion: IC demonstrated high agreement with histopathological analysis in the detection of atypical epithelial cells in unsuspected OSSN in Brazilian pterygia patients.

  16. Co-existing squamous cell carcinoma and hemangioma on the ocular surface of a cat.

    Science.gov (United States)

    Perlmann, Eduardo; da Silva, Enry Garcia; Guedes, Pedro Mancini; Barros, Paulo Sergio de Moraes

    2010-01-01

    A 14-year-old spayed female domestic short-haired cat was presented for evaluation of a mass in the right eye. Ophthalmic examination revealed a blind right eye and presence of two distinct masses: a pink and a red-to-brown mass, the latter occupying most of the cornea and part of the conjunctiva. Exenteration was performed under general anesthesia, and the ocular tissues were processed routinely for histopathology. Upon microscopic examination, a malignant epithelial neoplasm and a benign vascular neoplasm were present in the cornea. The conjunctiva and the third eyelid were also affected. Upon immunohistochemistry, the epithelial tumor was positive for cytokeratin and negative for vimentin and the endothelial tumor was negative for cytokeratin and positive for vimentin. A diagnosis of squamous cell carcinoma (SCC) and hemangioma was made. The SCC was affecting the cornea, bulbar conjunctiva (lateral and inferior) and the base of the third eyelid, whereas the hemangioma was affecting the cornea and medial limbus. To the authors' knowledge, this is the first report of concomitant SCC and hemangioma affecting the ocular surface in a cat.

  17. Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway

    DEFF Research Database (Denmark)

    Leffers, H; Madsen, Peder; Rasmussen, H H

    1993-01-01

    tissues showed that polypeptides comigrating with proteins 9124, 9125 and 9126 are ubiquitous and highly expressed in the brain. Stratifin, however, was present only in cultured epithelial cells and was most abundant in fetal and adult human tissues enriched in stratified squamous keratinising epithelium......We have identified a family of abundant acidic human keratinocyte proteins with apparent molecular masses ranging between 30,000 and 31,100 (isoelectric focussing sample spot proteins 9109 (epithelial marker stratifin), 9124, 9125, 9126 and 9231 in the master two-dimensional gel database of human...

  18. Protective effects of Lactobacillus plantarum on epithelial barrier disruption caused by enterotoxigenic Escherichia coli in intestinal porcine epithelial cells.

    Science.gov (United States)

    Wu, Yunpeng; Zhu, Cui; Chen, Zhuang; Chen, Zhongjian; Zhang, Weina; Ma, Xianyong; Wang, Li; Yang, Xuefen; Jiang, Zongyong

    2016-04-01

    Tight junctions (TJs) play an important role in maintaining the mucosal barrier function and gastrointestinal health of animals. Lactobacillus plantarum (L. plantarum) was reported to protect the intestinal barrier function of early-weaned piglets against enterotoxigenic Escherichia coli (ETEC) K88 challenge; however, the underlying cellular mechanism of this protection was unclear. Here, an established intestinal porcine epithelia cell (IPEC-J2) model was used to investigate the protective effects and related mechanisms of L. plantarum on epithelial barrier damages induced by ETEC K88. Epithelial permeability, expression of inflammatory cytokines, and abundance of TJ proteins, were determined. Pre-treatment with L. plantarum for 6h prevented the reduction in transepithelial electrical resistance (TEER) (Pplantarum were higher (Pplantarum was shown to regulate proteins of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. These results indicated that L. plantarum may improve epithelial barrier function by maintenance of TEER, inhibiting the reduction of TJ proteins, and reducing the expression of proinflammatory cytokines induced by ETEC K88, possibly through modulation of TLRs, NF-κB and MAPK pathways.

  19. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2017-02-14

    Head and Neck Squamous Cell Carcinoma; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

  20. Effect of Thin Prep(®) imaging system on laboratory rate and relative sensitivity of atypical squamous cells, high-grade squamous intraepithelial lesion not excluded and high-grade squamous intraepithelial lesion interpretations

    National Research Council Canada - National Science Library

    Koltz, Brooke R; Russell, Donna K; Lu, Naiji; Bonfiglio, Thomas A; Varghese, Sharlin

    2013-01-01