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Martel, André Bernard. "Targeting CD155 on Myeloid Derived Suppressor Cells to Prevent Postoperative Immunosuppression in Cancer Patients." Thesis, Université d'Ottawa / University of Ottawa, 2020. http://hdl.handle.net/10393/41151.
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Surgery, although required to treat most solid cancers, can increase tumour seeding and metastases. We have previously shown that surgery-induced myeloid derived suppressor cells (Sx-MDSCs) play an important role in this process by directly suppressing NK cells. The Sx- MDSCs increase significantly immediately after surgery but the exact mechanism by which Sx-MDSCs suppress NK cells is still unknown. In this work, we have discovered that CD155 poliovirus receptor is significantly and specifically upregulated on Sx-MDSCs following surgical stress but is minimally expressed on other immune cells. We also demonstrate that blocking CD155 in vivo leads to an improved NK cell phenotype, measured by DNAM-1 and NKG2D, and increased NK cytotoxicity. Additionally, ex vivo CD155 blockade significantly decreases the suppressive effect of Sx-MDSCs in cancer patients. Expansion of CD155 on Sx- MDSCs could be responsible for the profound postoperative NK cell suppression, which makes it a very appealing perioperative target for immunotherapy.
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Maier, Michael Klaus. "Studien zur Funktion von murinem CD155 bei der Migration von Leukozyten und der Entstehung einer humoralen Immunantwort." kostenfrei, 2007. http://d-nb.info/988269511/34.
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Baury, Béatrice. "CD155, un membre de la superfamille des immunoglobulines : homologies avec le gène Tage4 du rat, expression des formes membranaires et solubles." Nantes, 2002. http://www.theses.fr/2002NANT21VS.
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Notre projet a été axé autour de deux membres de la superfamille des immunoglobulines, le gène Tage4 de rat, dont la principale caractéristique est sa surexpression dans les tumeurs coliques chez le rat et la souris et le gène CD155 humain codant pour le récepteur du virus de la poliomyélite (PV). Nous avons déterminé l'organisation structurale du gène Tage4 en mettant notamment au point une technique de marche sur l'ADN pour isoler la région promotrice. Nos résultats ont souligné l'existence de nombreuses homologies structurales entre les gènes Tage4 et CD155. De plus, le produit du gène Tage4 permet l'entrée des virus utilisant le CD155 comme récepteur, à l'exception du PV. Ces homologies structurales et fonctionnelles suggèrent que le gène Tage4 est probablement l'orthologue du gène CD155. En outre, nous avons mis en évidence une surexpression du CD155 dans les carcinomes colorectaux. A l'instar de l'antigène carcinoembryonnaire (ACE), la surexpression du CD155 est un événement précoce dans la carcinogenèse colique. . .Our project focused on two members of the immunoglobulin superfamily, the rat Tage4 gene, which is overexpressed in rat and mice colon tumors, and the human CD155 gene coding for the poliovirus (PV) receptor. We have determined the structural organisation of the Tage4 gene by designing a DNA walking method to isolate the promoter region. Our results have underlined the existence of numerous homologies between Tage4 and CD155. Moreover, the product of the Tage4 gene can mediate entry into cells of the viruses, except PV, that use CD155 as a receptor. These structural and functional homologies suggest that the Tage4 gene is probably orthologous to the gene for CD155. Besides, we have shown by RT-PCR and immunohistochemistry that CD155 is overexpressed in colorectal carcinoma. As the carcinoembryonic antigen (CEA), the CD155 overexpression is an early event in colon carcinogenesis. However, unlike the CEA, the CD155 expression is not regulated by the interferon gamma nor by the nuclear receptor PPAR gamma (Peroxisome Proliferator-Activated Receptor). We have demonstrated the existence of CD155 secreted isoforms by immunoprecipitation in serum, in cerebrospinal fluid and in culture medium of polarised epithelial cell. .
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Jassam, Samah Ali. "Role of CD15 and CD15s in the cellular mechanisms of cancer cell metastasis from lung to the brain." Thesis, University of Portsmouth, 2016. https://researchportal.port.ac.uk/portal/en/theses/role-of-cd15-and-cd15s-in-the-cellular-mechanisms-of-cancer-cell-metastasis-from-lung-to-the-brain(de581581-027d-4106-9c23-9daa534d684f).html.
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Non-small cell lung cancer is one of the most common primary tumours to metastasise to the brain in adults. The underlining molecular mechanisms of brain metastasis are still not fully understood. Interactions between brain endothelial cells and cancer cells play key roles in brain metastasis. CD15 and CD15s are cell-cell adhesion molecules which interact with E-selectin which is expressed on endothelial cells and known to be involved in the leukocyte homing process as well as being implicated in metastasis with many non-CNS neoplasms. The aim of this project was to investigate the role of CD15 and CD15s in cancer cell adhesion to brain endothelial cells and transendothelial migration of lung cancer cells during brain metastasis. Expression of CD15, CD15s and CD62E was characterised in human primary and brain metastatic lung cancer cells using immunocytochemistry, flow cytometry, Western blot and immunohistochemistry in human tissue sections. Effects of CD15 and CD15s expression on NSCLC metastatic to brain were assessed using genetic manipulation (overexpression and knockdown) followed by functional assays. Both CD15 and CD15s were overexpressed and knockdowned and cell-cell adhesion was then examined using qualitative and quantitative adhesion assays, under both static and flow physiological conditions. Transendothelial migration potential was also assessed using a voltometer, Electric Cell-Substrate Impedance sensing system and cell-monitoring system CellZscope™. Findings showed that CD15 and CD15s were prominently expressed on metastatic lung cancer cells (SEBTA-001, SEBTA-005 and NCI-H1299) and weakly expressed on both primary lung cancer cells (COR-L105 and A549) and brain endothelium (hCMEC/D3). The highest expression of CD62E was observed on brain endothelium stimulated with TNF-α (25pg/ml) (p < 0.001). CD15, CD15s and CD62E expression was detected in human metastatic tissues. The absence of CD62E and immunoblocking and knockdown of CD15 and CD15s significantly reduced the adhesion of cancer cells under both static and shear stress conditions (p<0.0001). Overexpression of CD15 and CD15s significantly increased their adhesion on an endothelial monolayer (p < 0.001). Metastatic cancer cells were able to transmigrate through a brain endothelial monolayer compared to primary and glioblastoma multiforme (GBM) cells. Knockdown of CD15 and CD15s decreased the transendothelial migration potential of cancer cells while even primary lung cancer cells and GBM cells transmigrated following overexpression of CD15 and CD15s. These results confirmed the correlation between CD15 and CD15s in adhesion as well as transendothelial migration of cancer cells during cerebral metastasis.
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Zevian, Shannin Christine. "Structure-function analysis of Tetraspanin CD151." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/3022.
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The basement membrane protein laminin-332 (laminin-5) mediates both stable cell adhesion and rapid cell migration, and thus has the potential to either restrain or promote tumor cell metastasis. The major cellular receptors for laminin-332 are integrin α3β1, which mediates rapid tumor cell migration, and integrin α6β4, which often mediates stable cell attachment. Tetraspanin protein CD151 interacts directly with both α3β1 and α6β4 integrins and with other tetraspanins, thereby promoting α3β1 and α6β4 association with tetraspanin-enriched microdomains on the cell surface. To explore the possibility of selectively modulating tumor cell responses to laminin-332, we re-expressed a series of CD151 mutants in epidermoid carcinoma cells with near total, RNAi- mediated silencing of endogenous CD151. CD151's interactions with its integrin partners or its interactions with other tetraspanins were selectively disrupted by specific mutations in the CD151 large extracellular loop (EC2 domain) or in intracellular CD151 palmitoylation sites, respectively. CD151- integrin association and CD151-tetraspanin association were both important for α3β1 integrin- dependent initial adhesion and rapid migration on laminin-332. Remarkably, however, only CD151-integrin association was required for stable, α6β4 integrin-dependent cell attachment on laminin-332. In gap-filling assays, where CD151-silenced cells moved more rapidly than WT cells, again, only CD151-integrin association was required to restrict movement into the gap, suggesting that both α3β1 and α6β4 integrin must be able to associate with CD151 in order restrict group motility. In addition, we found that a QRD amino acid motif in the CD151 EC2 domain that had been thought to be crucial for CD151-integrin interaction is not essential for CD151-integrin association or for CD151's ability to promote several different integrin functions. These new data suggest potential strategies for selectively modulating migratory cell responses to laminin-332, while leaving stable cell attachment on laminin-332 intact.
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Romanets, Olga. "Study of the role of measles virus receptor CD150 in viral immunopathogenesis and characterization of novel CD150 isoform." Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2012. http://tel.archives-ouvertes.fr/tel-00923189.
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Measles virus (MV) causes an acute childhood disease, associated in certain cases with the infection of the central nervous system (CNS). MV induces a profound immunosuppression, resulting in high infant mortality. The major cellular receptor for MV is CD150, which binds MV hemagglutinin (MV-H). As dendritic cell (DC) dysfunction is considered to be essential for the MV immunopathogenesis, we analyzed consequences of MV-H interaction with DCs. We developed an experimental model allowing us to analyze the direct CD150-MV-H interaction in the absence of infectious context. This interaction caused the downregulation of surface expression of CD80, CD83, CD86 and HLA-DR molecules and inhibition of IL-12 production in DCs. DCs also failed to activate T cell proliferation. The CD150-MV-H interaction in DCs and B cells decreased the phosphorylation of JNK1/2, but not ERK1/2 kinases, after subsequent CD150 ligation with anti-CD150 antibodies. Moreover, MV-H by itself induced Akt phosphorylation via CD150 in DCs and B cells. Engagement of CD150 by MV-H in mice transgenic for human CD150 decreased the inflammatory reaction, contact hypersensitivity response, confirming the immunosuppressive effect of CD150-MV-H interaction in vivo. Furthermore, our studies revealed the CD150 expression in CNS tumors and identified the novel CD150 isoform, containing an additional 83bp exon expressed in lymphoid cells, DCs and CNS tumors. Although its isoforms remain intracellular in tumor cells, CD150 may represent a new marker for human brain tumors. Novel mechanism of CD150-induced immunosuppression and new CD150 isoform identified in these studies shed new light on its immunoregulatory role and CD150 isoform diversity and open perspectives for their clinical applications.
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Moyano, Rodríguez Yolanda 1992. "Mitosis exit regulation by Cdc5 and PP2A-Cdc55." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/668051.
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In this thesis we studied the role of PP2ACdc55 in the cytokinesis regulation and the contribution of Cdc5 kinase in the mitosis exit using budding yeast as model. Previously, it was suggested a putative PP2ACdc55 role in cytokinesis based on the elongated phenotype in absence of Cdc55. However, the PP2ACdc55 function during cytokinesis and its direct targets were not identified. In this thesis, we demonstrated that PP2ACdc55 regulates the IPC’s phosphorylation and their residence time at the bud neck. In addition, we showed that PP2ACdc55 coordinates actomyosin ring (AMR) contraction with septa formation.
As a second objective, we analyzed the Net1 residues to be phosphorylated by Cdc5 kinase contributing to the Cdc14 release from the nucleolus and mitotic exit progression.En esta tesis hemos investigado el papel de la fosfatasa PP2ACdc55 en la regulación de la citocinesis y la contribución de la quinasa Cdc5 en la salida de mitosis en la levadura de gemación. Previamente, se había sugerido un posible papel de la PP2ACdc55 en citocinesis basándose en el fenotipo elongado en ausencia de Cdc55. Sin embargo, la función de la PP2ACdc55 durante la citocinesis y sus sustratos no han sido estudiados. En esta tesis, hemos demostrado que la PP2ACdc55 regula la desfosforilación de las proteínas de IPC que regulan la citocinesis; así como, su tiempo de localización en el cuello. Además, hemos observado como la PP2ACdc55 realiza un papel en la coordinación de la contracción del anillo de actomiosina y la formación del septo. En cuanto a Cdc5, analizamos los posibles residuos de Net1 fosforilados por Cdc5 que contribuyen a la liberación de Cdc14 en la salida de mitosis.
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Maurik, Andre van. "The role of CD40-CD154 interactions in allograft transplantation." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249302.
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Dewitte, Antoine. "Plaquettes sanguines et insuffisance rénale aiguë : rôle du couple CD154/CD40 dans la constitution des lésions tubulaires." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0906.
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L’insuffisance rénale aiguë (IRA) est une pathologie fréquente en réanimation. Elle est associée à une mortalité et une morbidité importante. Le sepsis en est la cause la plus fréquente. La compréhension de la physiopathologie du sepsis et de ses complications a beaucoup progressé ces dernières années mais ne s’est pas encore traduite par des avancées thérapeutiques significatives en pratique clinique. Le paradigme d’une altération de la perfusion sanguine comme paramètre clé de la constitution des lésions rénales a ainsi été remis en question, plusieurs travaux révélant que le débit sanguin rénal n’est pas toujours altéré en cas de sepsis, et qu’une IRA peut se développer en cas de débit sanguin rénal préservé, voire augmenté. Le sepsis est caractérisé par de profondes perturbations de la réponse immunitaire et une réaction inflammatoire disproportionnée. A l’origine de l’atteinte rénale, l’inflammation et les altérations de la microcirculation sont maintenant considérés comme des mécanismes physiopathologiques fondamentaux. Au-delà de leur rôle dans l’hémostase, la contribution des plaquettes sanguines à la réponse inflammatoire, au maintien de l’intégrité tissulaire et à la défense contre les infections a considérablement élargi le spectre de leurs compétences et en a fait des acteurs physiopathologiques potentiels dans le sepsis. Les plaquettes sanguines exercent la plupart de ces fonctions grâce à l’expression de nombreux médiateurs membranaires ou solubles. Parmi eux, le CD154 tient une place particulière : les plaquettes sont une source essentielle de CD154 dans l’organisme et il joue un rôle central dans la réponse inflammatoire. Nous proposons dans ce travail un aperçu de ces avancées physiopathologiques récentes et nous discutons de la contribution des plaquettes et du CD154 dans les atteintes microcirculatoires et les défaillances multi-viscérales dans le sepsis. Nous nous sommes intéressés au rôle pro-inflammatoire du CD154 en conditions d’hypoxie au niveau de l’épithélium tubulaire rénal. Des données récentes soulignent en effet l’importance de l’hypoxie dans la réaction inflammatoire. Le contrôle de la production d’interleukine (IL)-6, une cytokine centrale de la réponse inflammatoire, par le CD154 a été étudié dans un modèle de culture de cellules épithéliales tubulaires (CET) rénales. Un modèle murin d’IRA par ischémie/reperfusion rénale a également été mis au point et appliqué à des souris déficientes en CD154 et CD40. Nos travaux révèlent que le CD154 induit fortement la sécrétion d’IL-6 par les CET en conditions d’hypoxie et que les souris déficientes en CD154 régénèrent plus rapidement leur épithélium tubulaire après ischémie/reperfusion rénale. Ces résultats pourraient ouvrir la voie à de potentielles pistes thérapeutiques pour la prise en charge des IRA d’origine septiqueAcute kidney injury (AKI) is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis is the most common cause of AKI. The understanding of sepsis pathophysiology and its complications has progressed significantly in recent years but has not yet been translated into significant therapeutic advances in clinical practice. The traditional paradigm that sepsis-induced AKI is linked to renal hypoperfusion has been challenged by recent evidences showing that renal blood flow is not universally impaired during sepsis,and that AKI can develop in the presence of normal or even increased renal bloodflow. Sepsis is characterized by profound alterations of the immune response and adisproportionate inflammatory response. Inflammation and microcirculatorydysfunction are now considered as fundamental pathophysiological mechanisms atthe origin of renal injuries. Beyond haemostasis, the contribution of platelets ininflammation, tissue integrity and defence against infections has considerablywidened the spectrum of their role and made them potential physiopathologicalactors in sepsis. Platelets fulfil most of these functions through the expression ofmembrane-bound or soluble mediators. Among them, CD154 holds a peculiarposition, as platelets represent a major source of CD154 and as CD154 is a centralregulator of inflammation. Here, we provide an overview of these recentpathophysiological advances and discuss the platelets and CD154 contribution tomicrocirculatory alterations in multi-organ dysfunction in sepsis. We investigated thepro-inflammatory role of CD154 under hypoxic conditions in the renal tubularepithelium as recent data highlight the importance of hypoxia in the inflammatoryreaction. We studied the control of interleukin (IL)-6 production, a key cytokineinvolved in inflammation, by CD154 in oxygen deprivation conditions using a kidneytubular epithelial (TEC) cell line model. We also studied a murine model of kidneyinjury after ischemia/reperfusion, a model that was applied in CD154 and CD40deficient mice. We found that CD154 is a potent inducer of IL-6 secretion by TEC inhypoxia and that CD154-deficient mice regenerate earlier the tubular epithelium afterischemia/reperfusion injury. These findings may provide potential avenues for septicAKI management and therapy
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Higa, Ryoko. "CD105 maintains the thermogenic program of beige adipocytes by regulating Smad2 signaling." Kyoto University, 2018. http://hdl.handle.net/2433/235056.
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Abbott, Rachel J. M. "Structural studies on CD55 and its human ligands." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491284.
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Human CD55 is a 70kDa protein found on the surface of serum-exposed cells: It has long been recognised as a regulator of the complement system, protecting self-cells by accelerating the decay of the C3 and C5 convertases. Much more recently CD55 has also been identified as a co-stimulator of T cells. I have used a wide range of biophysical techniques to study CD55 and its interaction with two human ligands, Bb and CD97. The interaction of CD55 with Bb has been investigated in the hope of contributing to the understanding of how CD55 accelerates decay of the alternative pathway C3 convertase (C3bBb). Surface plasmon resonance experiments have confirmed that CD55 binds to the vWF-A domain of Bb in the presence of Mg2 + and the KD of this interaction has been measured as 2.2JlM. Electron paramagnetic resonance has been used to obtain experimentally-derived distance restraints in order to model the complex between CD55 and the Bb vWF-A domain. CD55 has previously been shown to co-regulate T cell activity via its interaction with CD97, the archetypal member of the EGF-TM7 family of proteins. Using X-ray crystallography, I have determined the structure of EMR2, a very close homologue of CD97. Nuclear magnetic resonance-based chemical shift mapping of the CD55EMR2 interaction has allowed me to generate a model for the CD55-CD97 complex. The structure of this complex reveals that the T cell and complement regulatory activities of CD55 occur on opposite faces of the molecule. This suggests that CD55 is capable of promoting an adaptive immune response while simultaneously protecting self-cells from the innate immune system.
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Morgan, Joanne. "The role of CD55 in the tumour environment." Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275151.
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Tregaskes, Clive. "Characterization of the chicken orthologues of mammalian CD154 and CD40." Thesis, University of Reading, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493816.
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In mammals CD 154 (CD40 ligand, TNFSF5) and its cognate receptor CD40 (TNFRSF5) are essential for the generation of an adaptive immune response. To date very few members of either the TNF or TNF receptor superfamily have been identified in the chicken, and none of those that have share a high degree of homology with CD40 or CD 154. An EST derived from an activated chicken spleen cDNA library was identified as having a high homology to mammalian CD 154 sequences. A full-length cDNA containing this EST sequence was cloned, and used to generate a soluble form of the encoded protein. This soluble protein was to identify cells that expressed the receptor for this protein, and to clone a cDNA encoding this receptor. The protein was demonstrated to bind to chicken B cells and macrophages. The receptor to this putative chicken CD 154 protein shared a high degree of sequence homology to mammalian CD40 sequences. The sequence data alone was insufficient to identify these two proteins as orthologues of mammahan CD 154 and CCD40. The fusion protein was shown to have biological activity similar to its mammalian counterpart in three different bioassays, suggesting that these two proteins are functional and structural homologues of mammalian CD 154 and CD40.
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Bradley, Richard Grayson. "Development of cancer immunotherapeutics targeting complement regulatory protein CD55." Thesis, University of Nottingham, 2007. http://eprints.nottingham.ac.uk/10258/.
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CD55 is one of the complement regulatory/inhibitory proteins and is over-expressed on a wide range of solid tumours. CD55 is also known to be deposited within tumour stroma and is secreted in an active soluble form, mediated by matrix metalloproteinase-7. The complement cascade forms part of the innate immune system and culminates in cell lysis of targeted cells. As a complement regulatory protein, the primary function of CD55 is to accelerate the decay of complement components preventing formation of the membrane attack complex. CD55 is also known to be a ligand for the T cell early activation antigen CD97, and their interaction has been shown to inhibit the proliferation of activated T cells. This project aimed to develop anti-tumour immunotherapeutics aimed at exploiting CD55 as a tumour associated antigen. Initial strategies were to develop monoclonal antibodies, specific to identified epitopes from within the CD55 protein sequence, capable of binding, and neutralising CD55s decay accelerating activity. Developed antibodies would also have the potential to induce antibody dependent cell cytotoxicity, thus blocking CD55 protection of tumours and mediating an active anti-tumour response. Antibodies were raised specific to CD55 derived linear peptides, which have been used for the assessment of CD55 expression in breast tumour sections. Monoclonal antibodies failed to recognise natively expressed protein on viable tumour cells and alternate strategies were developed. An effective immunotherapy for the treatment of cancer would engage both cellular and humoral mediated responses for effective clearance of target cells. In order to achieve this, a DNA vaccine incorporating a human IgG Fc tail was developed expressing the active sites of CD55, containing HLA-A*201 restricted heteroclitic epitopes. The vaccines were used to immunise HLA-A*201 HHDII transgenic mice and CD55 specific responses were assessed. One of the vaccines analysed, elicited CD55 specific antibodies capable of recognising tumour cells in vitro and also generated epitope specific CD8+ T cell mediated lysis of epitope bearing cells. The frequency of CD55 specific T cells was obtained via antigen specific IFN gamma release ELISPOT assays and the cytokine profile of responses generated was assessed via luminex analysis. In conclusion, CD55 remains a viable target for immunotherapies aimed at CD55 bearing tumours. DNA vaccines encoding modified epitopes are capable or raising cellular and humoral responses to this antigen and further studies should be completed in order to determine anti-cancer effects in tumour bearing models.
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FitzGibbon, Hannah. "CD55 as a modulator of the adaptive immune response." Thesis, University of Nottingham, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438276.
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Griffiths, Meryn Ruth. "Investigation of the α3β1/CD151 complex association and function." Thesis, University of Birmingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397105.
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Baldwin, Gouri Seetharaman. "The CD151-α3β1 axis and its role in breast cancer progression." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3372/.
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This thesis investigates the role of CD151 in modulating the form and function of its integrin partners, α3β1 and α6β1/β4. Stable depletion of CD151 in the MDA-MB-231 (MDA-231) cell line, changed the glycosylation profile of α3β1, but not α6β1/β4 integrins. Glycosylation of CD151, tight association between CD151 and α3β1 integrin and recruitment into tetraspanin enriched microdomains (TERM) are all required for this effect and the intervention occurs during the first mannose trimming step within the ER. Further analysis showed that CD151 preferentially associates with α3β1 over α6β1/β4. CD151 mediated changes to glycosylation of α3β1 integrin decreased their ability to migrate towards Lm332 by ~90%. Sucrose density gradient assays showed α3β1 and α6β1/β4 are recruited by CD151 into the light fractions as part of a TERM as well as separate entities. Glyco-analysis of the tetraspanins themselves showed CD9 and possibly CD63 and CD82 to be phospho-mannosylated. Castanospermine treatment dramatically reduced the level of CD151, α3β1 and α6β1/β4 in these cells, indicating a novel therapeutic use. Depletion of various tetraspanins in MDA-231 altered their cell surface glycotope presentation and the cleavage profile of α6β1/β4 integrin; highlighting the role played by tetraspanins in post-translational modification of their partners.
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Rushworth, Stuart Anthony. "Analysis of CD40 mediated porcine endothelial cell activation by human CD154." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620387.
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O’Meara, Kellie Marcella. "Evaluation of Recombinant Salmonella Expressing CD154 for Enhanced Immune Responses in Commercial Turkeys." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1246567532.
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Kölbel, Beatrice [Verfasser]. "CD15-Fokus-Score: Ein immunhistochemisch basierter Score sowie die Mitentwicklung einer morphometrischen Software („CD15-Quantifier“) zur Infektionsdiagnostik in der periprothetischen Membran / Beatrice Kölbel." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1079840869/34.
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Alegretti, Ana Paula. "Expressão de proteínas reguladoras do complemento CD55/CD59 em células de sangue periférico de pacientes com lúpus eritematoso sistêmico." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2008. http://hdl.handle.net/10183/13674.
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CD55 e CD59 são proteínas de membrana ancoradas pela glicosilfosfatidilinositol que apresentam propriedades reguladoras da ativação da cascata do complemento. Esta regulação ocorre através da inibição da C3 convertase e prevenção da etapa final de polimerização do complexo de ataque à membrana, respectivamente. Pacientes com Lúpus Eritematoso Sistêmico com anemia hemolítica e linfopenia parecem apresentar uma deficiência adquirida de CD55 e CD59. Contudo, os mecanismos que modulam essa diminuída expressão continuam desconhecidos e o seu impacto nas manifestações do Lúpus Eritematoso Sistêmico necessita ser melhor estudado.CD55 and CD59 are glycosylphosphatidylinositos-anchored proteins with complement inhibitory properties, which inhibit formation of the C3 convertases and prevent the terminal polymerization of the membrane attack complex, respectively. Systemic Lupus erythematosus patients seem to have an acquired deficiency of CD55 and CD59 proteins associated with secondary autoimmune hemolytic anemia and lymphopenia. But the mechanisms remain unknown and its impact on the clinical manifestation of Systemic Lupus erythematosus needs to be more explored.
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Tosello, Annie-Carole. "Implication de la molécule CD55 dans l'activation du lymphocyte T." Aix-Marseille 2, 1998. http://www.theses.fr/1998AIX22086.
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La molecule cd55 est une glycoproteine liee a la membrane des lymphocytes t, par un motif glycosylphosphoatidylinositol (gpi). Elle a ete initialement impliquee dans la protection des cellules, de la lyse par le complement. De nombreuses donnees ont laisse supposer une implication de cd55 dans l'activation des lymphocytes, et notamment son association avec les src kinases, p56#l#c#k et p59#f#y#n. Ces kinases sont directement impliquees dans le mecanisme de transduction de signaux induits par le complexe cd3/tcr. Nous avons montre que la reticulation de cd55 induit la phosphorylation sur tyrosine de p56#l#c#k, p59#f#y#n, des chaines du complexe cd3-tcr, et de zap-70. En revanche, aucune phosphorylation de la plc-1 et aucun mouvement de calcium intracellulaire ne sont observes dans les memes conditions de stimulation. Par ailleurs, l'addition simultanee d'anticorps diriges contre cd55 et d'un ionophore a calcium entraine la secretion d'il-2 par les cellules t. Ces resultats suggerent qu'un signal calcique agit en synergie avec la voie cd55 pour conduire a la secretion d'il-2. Nous avons egalement demontre que la ligation de cd55 entraine l'activation de p21#r#a#s, rapportant pour la premiere fois la stimulation de ras par une molecule ancree par un motif gpi a la surface du lymphocyte t. Cette stimulation de ras est dependante du complexe cd3/tcr et independante de lck et de p72#s#y#k. Le gef de ras stimule par cd55 n'est toujours pas identifie. Neanmoins l'utilisation d'inhibiteurs de ptk nous a permis de montrer que l'activation de ras par cd55 est regulee par des tyrosine kinases. Kb50 qui est un inhibiteur specifique de lck, abolit en partie ce signal. Ce resultat en plus du fait que cd55 induit l'activation de ras dans des cellules deficientes en lck, suggere que cet evenement est controle par une autre src kinase, qui est probablement p59#f#y#n. Ces travaux suggerent que la voie de signalisation induite par cd55 recrute partiellement la voie de signalisation du complexe cd3/tcr.
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Baró, Sastre Bàrbara. "New substrates and functions of PP2A-Cdc55 phospatase in the mitotic exit." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/283260.
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La sortida de mitosis comprèn tots els processos de la mitosis que van des de la segregació de les cromàtides germanes a l’obtenció de dues cèl·lules filles genèticament idèntiques. A nivell molecular, les cèl·lules inicien diversos processos per inactivar la Cdk mitòtica, requisit imprescindible per acabar la mitosis i entrar en la següent fase G1. La sortida de mitosis en el llevat de gemmació, S. Cerevisiae, s’inicia amb l’activació del complex promotor d’anafase APCCdc20 i l’activació de la fosfatasa Cdc14. Dues rutes complementàries i seqüencials, FEAR (de l’anglès Cdc14 early anaphase release) i MEN (de l’anglès mitotic exit network), promouen l’alliberament i activació de la fosfatasa Cdc14 durant l’anafase, la qual es considera clau per eliminar l’activitat mitòtica de Cdk1 i sortir de mitosis. La fosfatasa Cdc14 es manté segrestada al nuclèol durant la resta del cicle cel·lular mitjançant la seva unió a la proteïna nucleolar Net1. A l’inici de l’anafase, la proteasa separasa hidrolitza el complex de cohesina, desencadenant així la separació de les cromàtides germanes i, alhora, coopera amb Zds1 per promoure la inhibició de la fosfatasa PP2ACdc55. La caiguda d’activitat PP2ACdc55 facilita la fosforilació de Net1 dependent de Cdk1, promovent així que Cdc14 s’alliberi al nucli. La quinasa polo, Cdc5, contribueix en aquest procés. A mesura que l’activitat mitòtica de Cdk1 disminueix, degut a l’acció d’APCCdc20 degradant ciclines mitòtiques i l’activitat de Cdc14, les cèl·lules activen la ruta MEN per mantenir Net1 fosforilat i Cdc14 actiu fins al final d’anafase. La ruta de MEN comprèn la GTPasa Tem1, i les quinases Cdc15 i Mob1-Dbf2. L’inici de la ruta està regulat pel complex Bfa1-Bub2, que manté Tem1 inactiu fins l’anafase, i per Lte1, que promou l’activació de Tem1. Un cop activa, la ruta de MEN allibera Cdc14 al citoplasma, on permet l’acumulació de l’inhibidor de Cdk1, Sic1, i on també activa el complex APCCdh1, el qual finalitza amb la degradació de les ciclines mitòtiques. Per tant, la completa activació de Cdc14 al final de l’anafase promou la inactivació de Cdk1 i contraresta les fosforilacions mitòtiques d’aquesta, permetent així la sortida de mitosis i entrada a G1.
Com la cèl·lula coordina la segregació cromosòmica amb la inactivació de la Cdk mitòtica és de gran interès, doncs errors en aquest procés provoquen la mort cel·lular. Així doncs, la descripció detallada dels mecanismes moleculars que regulen la sortida de mitosis tenen un gran potencial pel disseny de futures teràpies contra el càncer. El treball que es presenta en aquesta tesis doctoral aprofundeix en el paper de la fosfatasa PP2ACdc55 en la sortida de mitosis, fosfatasa que està emergent com a regulador clau del cicle cel·lular en organismes superiors. Resultats previs del grup suggereixen la implicació de la fosfatasa PP2ACdc55 en la iniciació de la ruta MEN i d’altres possibles funcions.
OBJECTIUS
1. Descriure el paper de la fosfatasa PP2ACdc55 en la regulació de la ruta MEN
2. Identificar nous possibles substrats i funcions de la fosfatasa PP2ACdc55 mitjançant un screening proteòmic.
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Brunner-Weinzierl, Monika. "Die Rolle von CD152 (CTLA-4) bei der Begrenzung von T-Zellantworten." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=972713417.
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Gao, Dingcheng. "On the pathophysiological significance of CD154-CD40 mediated leukocyte endothelial cell interaction." Doctoral thesis, [S.l.] : [s.n.], 2003. http://webdoc.sub.gwdg.de/diss/2003/gao/gao.pdf.
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Speck, Uwe. "Beeinflussung antigenspezifischer humaner T-Zellen durch die Blockade von CD152 (CTLA-4)." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=96633809X.
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Mars, Leonardus Theodorus. "Role of the CD154-CD40 axis in the modulation of autoimmune reactions." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326217.
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Cuss, Steven Martin. "The CD40-CD154 pathway in the development of Foxp3⁺ regulatory T cells." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610532.
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Brunner-Weinzierl, Monika. "Die Rolle von CD152 (CTLA-4) bei der Begrenzung von T-Zellantworten." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2004. http://dx.doi.org/10.18452/13941.
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Bei der adaptiven Immunantwort wird ein breites Repertoire an Effektor-T-Zellen gebildet, das sich durch spezifische und vielfältige funktionelle Fähigkeiten auszeichnet. Neben der Aktivierung der Immunantwort werden Mechanismen benötigt, die Immunantworten regulieren und abschalten können, um unerwünschte Immunreaktion zu verhindern. Die Arbeit befasst sich mit der Rolle von CD152 (CTLA-4), einem Homolog zu CD28, bei der Begrenzung von T-Zellantworten. Die Inhibition der Proliferationsbegrenzung der T-Zellen durch CD152 war ursprünglich auf eine späte Abschaltung der T-Zellproliferation zurückgeführt worden. Wir konnten zeigen, dass CD152 bereits die T-Zellaktivierung abschalten kann und somit die Aktivierungsschwelle der T-Zelle heraufsetzt. Wir konnten auch zeigen, dass CD152 die frühe T-Zellproliferation auf zwei Ebenen inhibiert: Durch die Transkriptionsinitiierung des autologen, Proliferation-induzierenden Zytokins IL-2 und durch die Expression von G1-Kinasen, die für das voranschreiten des Zellzyklus unerläßlich sind. Bisher war es nicht möglich, individuelle, CD152-oberflächen-exprimierende T-Zellen zu detektieren. Um die Expression von CD152 auf der Oberfläche von T-Zellen zu analysieren, haben wir eine sensitive Färbemethode für Oberflächen-exprimiertes CD152 etabliert. Wir konnten damit zeigen, dass während einer antigen-spezifischen Stimulation Zellmembran-gebundenes CD152 lediglich auf einer Subpopulation von aktivierten Zellen (CD152+ T-Zellen) exprimiert wird. Isolierte, aktivierte CD152+ T-Zellen waren im Gegensatz zu aktivierten CD152- T-Zellen bei Restimulation in ihrer Proliferation inhibiert. Dies zeigt auch, dass CD152 in der Lage ist, bereits aktivierte T-Zellen zu inhibieren. Die heterogene Expression von CD152 auf der Oberfläche lässt vermuten, dass die CD152 exprimierenden Zellen, wenn sie ein CD152-Signal bekommen, eine andere Zelldifferenzierung einschlagen als Zellen ohne CD152. Wiederholte oder chronische Aktivierung von Th-Zellen führt zu einer Form von Apoptose, dem Aktivierungs-induzierter Zelltod, gegen den Th2-Zellen resistent sind. Aktivierte Th2-Zellen exprimieren, im Gegensatz zu Th1-Zellen, häufiger CD152 auf ihrer Oberfläche. Wir konnten zeigen, dass CD152-Kreuzvernetzung von aktivierten T-Zellen direkt Resistenz gegen Apoptose vermittelt. Dies geschieht, indem ein Signaltransduktionsmolekül, die PI3´Kinase, aktiviert wird. Dies führt zur Inaktivierung von Apoptose-unterstützenden Molekülen (Phosphorylierung von FKHRL1 und Herunterregulation von FasL) und zur Induktion des Apoptose-verhindernden Moleküls Bcl-2. Vermeidung von Apoptose ist eine zentrale Voraussetzung zur Induktion von Gedächtniszellen. CD152 exprimierende Zellen wären somit gute Kandidaten, um zu Gedächtniszellen zu differenzieren. Um die Rolle von CD152 bei der späten T-Zelldifferenzierung in vivo untersuchen zu können, wurde das CD152 Gen konditionell in der Maus mutagenisiert.During adaptive immune responses a broad repertoire of effector T-cells is generated, characterized by diverse functional capabilities. Besides activation of the immune response other mechanisms are needed in order to regulate and terminate responses, thus preventing unwanted immune reactions. Here I focus on the role of CD152 (CTLA-4), a homologue of CD28, in the limitation of T-cell responses. Inhibition of T-cell-proliferation by CD152 was originally attributed to a late regulation of the T-cell proliferation. We now show that CD152 is already able to prevent the activation of T-cells and to set the threshold for their activation. We also show that CD152 inhibits T-cell activation in two ways: It inhibits the induction of the growth-factor IL-2 and it inhibits the expression of G1-kinases mandatory for the progression of the cell cycle. Until now, it has not been possible to detect individual T-cells expressing CD152 at their surface. To analyze the expression of CD152 at the surface of individual cells, we developed a sensitive staining method. Using this technique we could show that antigen-specific stimulation of T-cells leads to the expression of surface-bound CD152 only on a fraction of the activated T-cells. Isolated, activated CD152+ T-cells were inhibited in their proliferation whereas CD152- T cells were not. This also shows that CD152 is indeed able to inhibit already activated T-cells. The heterogenous expression of CD152 at the cell surface of already activated T-cells also suggests that CD152+ T-cells will differentiate differently compared to CD152-T-cells. Repeated or chronic activation of Th-cells leads to one form of apoptosis, activation-induced cell death (AICD), against which Th2-cells are resistant. Activated Th2-cells express surface CD152 at higher frequencies than Th1-cells. We show here, that CD152-crosslinking of activated T-cells directly induces resistance against AICD by a mechanism requiring PI3´kinase. This leads to the inactivation of pro-apoptotic molecules (phosphorylation of FKHRL1 and downregulation of FasL). It also leads to the induction of the survival molecule Bcl-2. Prevention of apoptosis is a central prerequisite for the generation of memory cells. Therefore, surface CD152+ T-cells might be good candidates to differentiate into memory cells. To investigate the role of CD152 during the differentiation of T-cells in vivo, the CD152 gene was conditional mutagenese of the CD152 gene was generated.
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Dourado, Keina Maciiele Campos. "Papel da Endoglina/CD105 em leucemias agudas: um potencial alvo para intervenção terapêutica." Universidade Federal da Bahia, 2016. http://repositorio.ufba.br/ri/handle/ri/21386.
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O tratamento das leucemias agudas continua sendo um grande desafio clínico devido, principalmente à heterogeneidade e alta toxicidade da terapia padrão utilizada. Dessa forma, novos alvos terapêuticos são urgentemente necessários e os anticorpos monoclonais tem surgido como uma das opções terapêuticas mais promissoras. A endoglina, também conhecida como CD105, é um receptor da superfamília do TGF-β, expresso nas células-tronco hematopoiéticas (HSC) de todos os sítios hematopoiéticos, incluindo a medula óssea, onde é descrita como um marcador para HSC de longo prazo. Apesar da expressão de CD105 ter sido relacionada a diversos tipos de tumores sólidos, principalmente devido ao papel desse receptor na angiogênese, relativamente pouco é conhecido em relação a expressão de CD105 e a sua função em neoplasias hematopoiéticas. Este estudo revelou alta expressão de endoglin na maioria dos blastos de pacientes com leucemia mieloide aguda (LMA) e leucemia linfoblástica aguda (LLA). Utilizando um modelo de xenotransplante, verificamos que as blastos CD105+ possuem uma actividade leucemogênica superior em comparação com a população de CD105-. Adicionalmente, investigamos se o bloqueio da endoglina, usando TRC105, poderia resultar em uma opção terapêutica para tratamento das leucemias agudas e descobrimos que na LMA, o TRC105 impediu o engraftment de blastos primários e inibiu a progressão da leucemia após o estabelecimento da doença, mas na LLA, o TRC105 sozinho foi ineficaz devido à uma maior secreção da forma soluvél da endoglina (sENG). No entanto, tanto na LLA quanto na LMA, TRC105 potencializou o efeito terapeutico da quimioterapia padrão e inibiu a progressão da doença, indicando que TRC105 pode representar uma nova opção terapêutica para LLA e LMA.
Successful treatment of acute leukemia remains a clinical challenge due to the toxicity and the relatively poor responses to the current standard therapy. Thus, treatments that address novel therapeutic targets are urgently needed and, for this purpose, monoclonal antibodies have been one of the most promising strategy once they are able to deliver their therapeutic effects with minimal toxicity. Endoglin, also known as CD105, is a receptor of the transforming growth factor-beta (TGF-β) superfamily that has been found expressed in hematopoietic stem cells (HSCs) from all hematopoietic sites, including the bone marrow, in which it is described as a marker for long-term HSC. CD105 is also found to be expressed in several cancers. However, because CD105 expression has been studied mostly in the context of solid tumors and angiogenesis, relatively little is known about CD105 expression and role in hematopoietic malignancies. We identified endoglin expression on the majority of blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL). Using a xenograft model, we find that CD105+ blasts are endowed with superior leukemogenic activity compared to the CD105- population. We test the effect of targeting this receptor using the monoclonal antibody TRC105, and find that in AML, TRC105 prevented the engraftment of primary AML blasts and inhibited leukemia progression following disease establishment, but in B-ALL, TRC105 alone was ineffective due to the shedding of soluble CD105. However, in both B-ALL and AML, TRC105 synergized with reduced intensity myeloablation to inhibit leukemogenesis, indicating that TRC105 may represent a novel therapeutic option for B-ALL and AML.
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Degos, Clara. "Contrôle et modulation de la réponse immunitaire par Brucella abortus." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4069/document.
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Brucella est une bactérie pathogène intracellulaire responsable d'une maladie, la brucellose. Sa capacité à établir une infection chronique est due aux mécanismes qu'elle déploie pour inhiber la réponse immunitaire. Parmi les cellules infectées, les cellules dendritiques (DC) et les macrophages (MO) jouent un rôle primordial dans l'induction de la réponse immunitaire. Nous avons étudié le rôle d'un récepteur des DC, des lymphocytes T (LT), MO : CD150. Il participe à l'activation des LT et il a été montré que CD150 est capable de reconnaître des protéines de l'enveloppe bactérienne, ce qui conduit à une augmentation de son expression à la membrane des MO. Nous avons découvert que l'expression de CD150 sur les DC dérivées de moelle osseuse (BMDC) augmente en présence d'extraits membranaire de Brucella, sauf quand ces derniers proviennent d'un mutant pour Omp25 (∆omp25). L'infection de BMDC par ∆omp25 active les BMDC en termes d'expression de molécules de co-stimulation, d'ARNm pro-inflammatoires (cytokines) et de translocation de NF-κB dans le noyau. En comparant avec une souche sauvage de Brucella, l'activation par ∆omp25 est plus importante. En absence de CD150 la translocation de NF-κB dans les BMDC infectées par la souche sauvage est aussi importante que celle induite par l'infection par ∆omp25. In vivo CD150 contrôle la réplication de Brucella dans la rate de souris infectées. Nous avons démontré que CD150 est capable de lier Omp25. Nous avons identifié un nouveau mécanisme par lequel Brucella inhibe l'activation des DC : la liaison d'Omp25 à CD150. Ce récepteur joue un double rôle puisqu'il est aussi crucial dans le contrôle de la survie de Brucella in vivoBrucella is a pathogenic intracellular bacterium responsible for a disease, brucellosis. The ability of Brucella to establish a chronic infection is linked to the mechanism it uses to inhibit immune response. Among Brucella infected cells, dendritic cells (DC) and macrophages play a crucial role in the induction of an immune response. We studied the role of one receptor present at the DC, T cells, macrophages surface: CD150. This molecule participates at the T cell activation and it was shown recently that CD150 can recognize bacterial membrane proteins which lead to its own upregulation. We discovered that CD150 expression onto bone-marrow derived DC (BMDC) is increased when these cells are treated with Brucella membrane extracts, except when those extracts are coming from a mutant for Omp25(∆omp25), a Brucella membrane protein. BMDC infection with ∆omp25 leads to BMDC activation regarding co-stimulatory molecule expression, cytokines and chemokines secretion, pro-inflammatory mRNA expression and NF-κB translocation within the nucleus. In comparison with infection with the wild type strain, ∆omp25 induces a higher activation of BMDC. In absence of CD150, NF-κB translocation within the nucleus of infected-BMDC is the same between the wild type strain and ∆omp25. In vivo, CD150 controls Brucella replication in the spleen of infected mice, and Omp25 infection seems to trigger a higher inflammation in control mice. We finally demonstrate that CD150 binds Omp25. Here, we identified a new mechanism by which Brucella is able to inhibit DC activation: binding of Omp25 to CD150. This receptor plays a dual role since it is also required for controlling Brucella growth in mice
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Spence, Philip James. "The role of CD154 in the life of a Foxp3⁺ regulatory T cell." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611299.
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Elzatma, Essameddin. "Study of the regulatory receptor CTLA-4 (CD152) in human myeloid derived cells." Thesis, University of Essex, 2009. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548590.
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Kim, Ji Hye. "microRNA regulation of CD44 and CD151 in hepatocellular carcinoma: Implications for novel therapies." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1436954441.
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Villeneuve, Julien. "CD154 et adaptation cellulaire au stress métabolique : exemple de la stéatose hépatique expérimentale." Bordeaux 2, 2008. http://www.theses.fr/2008BOR21591.
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La stéatopathie métabolique est un problème majeur en santé publique. Sa prévalence est importante et le risque de progression vers la cirrhose et le carcinome hépatocellulaire en font toute la gravité. Un élément histopathologique caractéristique est une stéatose hépatique, résultant de l'accumulation de triglycérides dans l'hépatocyte. Les mécanismes responsables ne sont pas compris mais l'implication du stress du réticulum endoplasmique (RE) est de plus en plus soulignée. Un apport excessif de lipides au niveau de l'hépatocyte s'accompagne d'un déséquilibre de l'homéostasie du RE appelé stress du RE. Le stress du RE se manifeste par l' "Unfolded Protein Response" (UPR), correspondant à l'activation de voies de signalisation dont les effecteurs visent à adapter les capacités fonctionnelles du RE. Le stress du RE et la réaction inflammatoire sont liés, les mécanismes en restant mystérieux. Le CD154 est un acteur clé de la réaction inflammatoire et c'est pourquoi nous avons étudié son rôle dans les mécanismes de la stéatose hépatique. Les souris dont le gène codant pour le CD154 a été invalidé développent une stéatose dans un contexte de régime riche en huile d'olive. En analysant les mécanismes sous-jacents, nous avons montré que le CD154 amplifiait l'UPR et, particulièrement, augmentait la génération d'un effecteur de l'UPR, la forme épissée de la "X-box-binding protein 1". Le CD154 favorise ainsi l'adaptation cellulaire en intervenant sur l'homéostasie du RE via le contrôle de l'UPR. Ce travail a mis en lumière un nouveau rôle biologique pour le CD154 et ce dernier apparaît comme un médiateur important dans l'histoire naturelle de la stéatopathie métaboliqueNon Alcoholic Fatty Liver Disease (NAFLD) is a major public health concern. Its prevalence is high and its severity is related to the risk of transition towards cirrhosis and hepatocellular carcinoma. A distinctive histological feature of NAFLD is liver steatosis, resulting from the triglyceride accumulation in hepatocytes. The mechanisms underlying liver steatosis are not yet understood, however, the involvement of the endoplasmic reticulum (ER) stress is being increasingly emphasized. Excess lipid input to the hepatocyte disrupts the ER homeostasis, its loading overwhelming its processing abilities, leading to what is termed the ER stress. ER stress activates the unfolded protein response (UPR) that corresponds to the activation of specific signalization pathways, whose effectors aim at adjusting the functional capacities of the ER. ER stress and the inflammatory reaction are linked, but the underlying mechanisms remain obscure. CD154 is a key mediator of inflammation and, therefore, we studied its involvement in the mechanisms leading to liver steatosis. CD154 knock-out mice developed a steatosis when fed with an olive oil-rich diet. When studying the corresponding mechanisms, we found that CD154 amplified the UPR and, more specifically, increased the unconventional splicing of an effector of the UPR, the X-box binding protein 1. Hence, CD154 increases cell adaptation by controlling the ER homeostasis. Our work highlights a new biological function for CD154, which appears to be an important mediator in the natural history of NAFLD
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Guo, Baoqiang. "CD105 expression and its effects on TGF-beta signalling, angiogenesis and cell behaviour." Thesis, University of Manchester, 2003. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.502933.
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CD 105 (endoglin), a 180kDa homodimeric transmembrane glycoprotein, is highly expressed in angiogenic endothelial cells (ECs) and is an important component of the transforming growth factor-beta (TGF-beta) receptor complex. In an attempt to understand the regulation of CD 105 expression and the molecular mechanism by which it exerts its effect on angiogenesis, human dermal microvascular endothelial cells (HDMECs) and CD 105 transfected rat myoblasts were utilised as an in vitro model with the following results: (1) TGF-beta1 increased CD105 expression in HDMECs at the transcriptional level. Flow cytometry. Western and Northern blot analysis showed that CD 105 expression was increased in HDMECs. When pXP2 plasmid DNA containing a full-length CD 105 promoter was transiently transfected into HDMECs, a marked response to TGF-beta1 was observed, implying that TGF-beta1 upregulates CD 105 expression at the transcriptional level. In contrast, TNF-alpha reduced CD 105 protein in HDMECs independent of its transcriptional regulation. (2) CD105 expression was increased by CoCl2 and overexpression of CD105 regulated HIF-1 transcriptional activity. CD 105 expression in HDMECs was demonstrated by flow cytometry and Western blot analysis to be increased by C0CI2 which is a specific inducer of hypoxia inducible factor-1 (HIF-1). pXP2 plasmids containing CD 105 promoters differing in length, were transiently transfected into HDMECs. They all showed similar luciferase activity in response to CoCl2, implying that the HIF-1 binding site is located in the shortest promoter sequence (-50/+350). Only one 5'-ACGTG-3' consensus sequence was observed in it, and this was responsible for HIF-1 binding and transcriptional activation in response to CoCl2. A hypoxia response element (HRE)-containing plasmid, (HRE)3-Luc, was transiently transfected into mock and CD 105 rat myoblast transfectants. It was demonstrated that overexpression of CD 105 increased luciferase activity in response to CoCl2, suggesting that overexpression of CD 105 increased HIF-1 transcriptional activity. (3) CD105 was involved in proliferation of ECs. A reduction in CD105 expression by CD 105 antisense oligodeoxynucleotide (AS-ODN) led to inhibition of EC proliferation, suggesting that CD 105 expression in HDMECs was involved in the regulation of their proliferation. (4) CD105 modulated TGF-beta1 signalling through both Smad3 and JNK signalling pathways. Overexpression of CD 105 in rat myoblast transfectants antagonised TGF-beta1 mediated inhibition of cell proliferation and reduced TGF-beta1-mediated p3TP-Lux (PAI-1 promoter) luciferase and (CAGA)12-Luc luciferase activity. The CAGA sequence is specific for SmadS and Smad4 binding, implying that CD 105 is involved in inhibition of TGF-beta1/ SmadS signalling. As demonstrated in immunoprecipitation and translocation assays, CD 105 overexpression reduced phosphorylation and nuclear translocation of SmadS. CD 105 expression also resulted in high phosphorylation of JNK1, which is able to activate c-Jun. It is known that c-Jun inhibits transcriptional activity of SmadS on CAGA sites, implying that CD 105 may also inhibit the transcriptional activity of SmadS through JNK. (5) Overexpression of CD105 in rat myoblasts was involved in cell morphology, spreading and persistent directional movement. Mock and CD 105 rat myoblast transfectants were cultured in un-coated plastic dishes in DMEM medium supplemented with 10% FCS. Mock cells displayed polygonal morphology. CD 105 transfectants showed fibroblastoid elongated forms and tended to align in parallel cords. Inununofluorescence showed that strong CD 105 staining was found in adhesion sites in CD 105 transfectants. Sequential observation of the growth characteristics of CD 105 transfectants and wound healing assays showed directional movement. CD 105 overexpression led to cell spreading in serum-free DMEM medium. It was blocked by a RGD containing peptide but not a RAD one. The anti-CD 105 mAb, E9, increased spreading of CD 105 transfectants, which was blocked by a RGD containing peptide but not a RAD one. These data suggest that CD 105 may change cell morphology through interaction of its RGD in the extra-cellular domain with integrins. In summary, a hypothesis was proposed that CD 105 mediated a transition of TGF-beta1 from anti-angiogenesis to pro-angiogenesis by inhibiting ALK5(T?RI)/Smad3 leading to a relative increase in ALK1/Smad5 signalling. This obviously requires further work for its validation.
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Lukacik, Petra. "Complement regulation at the molecular level : crystallographic structure determination of CD55." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404175.
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Richards, Elliott Grant. "The Role of Decay Accelerating Factor in the Pathogenesis of Endometriosis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1619689609524397.
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Su, Ting-Cheng. "Regulation of pheromone response in saccharomyces by Ste12-PRE interaction and TOR-Cdc55 signaling." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43645.
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Ste12 is the key regulator in the yeast pheromone response pathway and works as an
important model for understanding gene regulation by MAP kinase cascades. In this
thesis I address how the binding strength of pheromone-response element (PRE)
sequences, their orientation, and intervening nucleotide distance between two PREs
govern the overall response to pheromone. I found that Ste12 binds as a monomer to a
single PRE in vitro, and that two PREs upstream of a minimal core promoter cause a
level of induction proportional to their relative affinity for Ste12 in vitro. Although
consensus PREs are arranged in a variety of configurations in the promoters of
pheromone responsive genes, I found there are severe constraints with respect to how
they can be positioned in an artificial promoter to cause induction of gene expression.
Two closely-spaced PREs can induce transcription in a directly-repeated or tail-to-tail
orientation, while PREs separated by at least 40 nucleotides are capable of inducing
transcription when oriented in a head-to-head or tail-to-tail configuration. By comparing
the constraints defined by analysis of artifical promoters, I found that a single PRE can
cause response to pheromone induction in combination with a properly oriented PRE-like
sequence.
By studying Ste12 multimerization, I found that this process might involve
dephosphorylation on Ste12 to regulate the expression of pheromone-regulated genes. I
discovered that Cdc55, a regulatory subunit of protein phosphatase IIA, can affect
pheromone response. In the cdc55 null mutant I observed decreased expression level of a
reporter gene and decreased mating efficiency. Cdc55 directly or indirectly alters the phosphorylation status of Ste12, as I observed hyperphosphorylated Ste12 in the cdc55
mutant compared to wild type. The effect of Cdc55 is independent of the pheromone
response MAP kinase pathway, but was found to be controlled downstream of TOR.
Analysis of artificial reporter genes and a candidate set of pheromone responsive
promoters demonstrated that TOR-Cdc55 signaling regulates a distinct subset of
pheromone-responsive genes. These results demonstrate a new regulatory circuit for the
pheromone response controlled by the TOR signal pathway, which operates to control
mating of yeast haploids in response to nutrients.
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Blumenthal, Antje [Verfasser]. "Charakterisierung der Tetraspanine CD9, CD81 und CD151 in einer permanenten murinen Podozytenzelllinie / Antje Blumenthal." Greifswald : Universitätsbibliothek Greifswald, 2012. http://d-nb.info/1024147320/34.
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Hewitson, James Philip. "The role of the CD40/CD154 pathway in protective immune responses against Schistosoma mansoni." Thesis, University of York, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424528.
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Voss, Martin August. "An investigation into tetraspanin CD151 as novel prognostic markers in poor outcome endometrial cancer." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/5228/.
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Background: Type II endometrial carcinoma, sarcoma and carcinosarcoma account for 10% of uterine malignancies but 50% of recurrences. Survival at recurrence is poor and better prognostic markers are needed to guide therapy. The prognostic significance of the novel markers clusterin and tetraspanin CD151 were evaluated in a cohort of poor outcome endometrial malignancies, along with oestrogen receptor, progesterone receptor, p53 and human epidermal growth factor receptor 2. Immunohistochemistry profiles and survival outcome between grade 3 endometroid cancers and type 2 cancers were compared. Material and Methods: Tissue microarrays constructed from 156 poor outcome uterine malignancies, tested with immunohistochemistry and staining were correlated with clinicopathological, mortality and survival data. Results: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma (USPC+CC) compared to grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma. All other markers were not prognostic for survival. Except for CD151, there was no significant difference in marker positivity, age, stage or survival between G3 EEC and UPSC+CC. Conclusion: CD151 is a novel marker in type 2 cancers that may guide therapeutic decisions. These data also suggest that grade 3 EEC is better characterised as a type II endometrial cancer and may benefit from similar treatment.
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Seung, Edward. "CD40-CD154 Blockade Facilitates Induction of Allogeneic Hematopoietic Chimerism and Transplantation Tolerance: A Dissertation." eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/103.
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Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Establishment of hematopoietic chimerism created by stem cell transplantation has been shown to prevent and cure a number of autoimmune diseases and induce the most robust and long-lasting form of transplantation tolerance known. However, the realization of the vast clinical potential of hematopoietic chimerism for induction of transplantation tolerance has been impeded by the toxicity of the host conditioning regimen and the development of graft-versus-host disease (GVHD). This thesis describes the development of stem cell transplantation protocols that 1) reduce the host conditioning regimen; and 2) abrogate the development of GVHD. When applied to the treatment of autoimmune diabetic NOD mice, a model of type 1 diabetes, stem cell transplantation was able to 3) prevent autoimmune recurrence; and 4) permit curative pancreatic islet transplantation.
I first describe a tolerance-based stem cell transplantation protocol that combines sub-lethal irradiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, I established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. All chimeric mice treated with anti-CD154 antibody remained free of graft vs.host disease (GVHD) and accepted donor-origin but not third party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. I conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sub-lethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as two injections of anti-CD154 antibody. I also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts.
In order to further reduce the impediments associated with the implementation of allogeneic hematopoietic chimerism as a therapeutic modality, I adapted a costimulation blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The protocol combines a donor-specific transfusion (DST) with anti-CD154 antibody to induce peripheral transplantation tolerance. When applied to stem cell transplantation, administration of DST, anti-CD154 antibody, and allogeneic bone marrow led to hematopoietic chimerism and central tolerance with no myeloablation (i.e. no radiation) and no GVHD in 3 different strains of mice. The development of donor-specific tolerance in this system was shown to involve deletion of both peripheral host alloreactive CD8+ T cells and nascent intrathymic alloreactive CD8+ T cells. In the absence of large numbers of host alloreactive CD8+ T cells, the cell transfusion that precedes transplantation need not be of donor-origin, suggesting that both allo-specific and non-allo-specific mechanisms regulate engraftment. Agents that interfere with peripheral transplantation tolerance partially impair establishment of chimerism. I conclude that robust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of host myeloablative conditioning using a peripheral transplantation tolerance protocol.
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Powell, Robert. "Studies on the interaction of enteroviruses with soluble decay-accelerating factor (CD55)." Thesis, University of Reading, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286023.
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Sutavani, Ruhcha V. "CD55 costimulation induces differentiation of human T regulatory type - 1 (Tr1) cells." Thesis, University of Nottingham, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727951.
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Unlike other helper T cells, the co-stimulatory ligands responsible for T regulatory type-1 (Trl) cells differentiation remain undefined. Understanding the molecular interactions driving peripheral Trl differentiation is important because Trls potently regulate immune responses, by IL-10 production. In this study we show that co-stimulation of human naïve CD4+ cells through the CD97-CD55 interaction drives Trl activation, expansion and function. T cell activation and expansion was equipotent with CD55 or CD28 co-stimulation, however CD55 co-stimulation resulted in two IL-10 secreting populations. The majority of the IL-10 was secreted by the minor, Trl population (IL-10high IFN-y- IL-4-, <5% cells) that express Trl markers CD49b, LAG-3 and CD226. This Tr 1 phenotype was not re-stimulated by CD28. But on CD55 re-stimulation, Trls proliferated and maintained their differentiated IL-10 high phenotype. The Trls significantly suppressed effector T cell function in an IL-10 dependent manner. The remaining (>95%) cells adopted a Thl- like IFN-y + phenotype. However, in contrast to CD28 derived This, CD55 derived This demonstrated increased plasticity with the ability to co-express IL-10 when re-stimulated through CD55 or CD28. These data identify CD55 as a novel co-stimulator of human Trls and support a role for alternative co-stimulatory pathways in determining the fate of the growing number of T helper populations. In this study we also show a defect in Trls in the autoimmune disease Multiple Sclerosis (MS). In response to CD55 costimulation, naïve CD4+ cells from a cohort of MS patients did not differentiate into Trl cells as normal, however the CD55 induced Thl response was unaffected. These patients showed persistent lack of an IL-10h1gh Trl population on primary and secondary CD55 costimulation. Also, MS patients mounted stronger IFN-y responses compared to healthy controls. These data demonstrate an altered immune balance in MS and highlight a defect in the Trl response as a contributing factor of this change. Overall, this study demonstrates that CD55 acts as a potent co-stimulator and activator of human naive CD4+ cells resulting in the differentiation of a discrete Trl population that inhibits T cell function in an IL-10 dependent manner and maintains the Trl phenotype upon re-stimulation, in healthy individuals. However, there is a defect in this normal Tr 1 response in the autoimmune condition Multiple Sclerosis.
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Xavier, Ruth Lopes de Freitas. "Estudo da angiog?nese pelo CD105 e FvW no carcinoma epiderm?ide oral e sua rela??o com o estadiamento cl?nico do tumor." Universidade Federal do Rio Grande do Norte, 2008. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17100.
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Previous issue date: 2008-02-28Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
The purpose of this study was to assess the immunohistochemical expression of CD105 and FvW antibodies in the angiogenesis of oral epidermoid carcinoma (OEC), correlating it with the TNM clinical staging system, seeking a better understanding of its biological behavior and use as an indicator of prognosis.The sample consisted of 30 epidermoid carcinoma (EC) cases, 10 of the floor of the mouth, 10 of the retromolar region and 10 of the tongue, in addition to 10 cases of pyogenic granuloma, which made up the control group. The results showed that mean microvessel counts (MVC) were correspondingly higher in the pyogenic granuloma group (CD105 = 57.26 vessels and FvW = 39.64) than in the EC group (CD105 = 10.09 and FvW = 12.20) and that the differences were statistically significant between the groups for each of the angiogenic biomarkers (p = 0.002 for CD105 and p< 0.001 for FvW). CD105 had better positivity in the pyogenic granuloma group (mean = 57.26 vessels) and for EC, FvW had the highest expression (mean = 12.20 vessels). With respect to EC, the most affected age group was between 51 and 70 years (n = 14; 46.7%), with a representative MVC for both markers. No statistically significant difference was found between the sexes for any of the markers (p = 0.967 for CD105 and p = 0.744 for FvW). Mean CD105 levels were much higher in patients with stage T3 and T4 (17.13) and lower in those with stage N+ (6.36). Mean FvW levels were higher in the patients with stage T1 and T2 (12.23) and lower in patients with T3 and T4 (12.10), but without a statistically significant difference. In regard to anatomic location, a statistically significant difference was observed between FvW sites, with a statistically significant difference between floor of the mouth cases and those located in the retromolar region (p =0.013). Therefore, this study suggests that CD105 expression in OEC angiogenesis, in contrast to other types of malignant neoplasias, may not be correlated with prognosis and tumor aggressiveness, whereas FvW was a more effective antibody for staining this lesion
Nesta pesquisa buscou-se avaliar a express?o imunoistoqu?mica dos anticorpos CD105 e FvW na angiog?nese do Carcinoma Epiderm?ide Oral (CEO), correlacionando-o com o estadiamento cl?nico pelo sistema TNM, visando uma melhor compreens?o do seu comportamento biol?gico e utiliza??o como indicador de progn?stico. A amostra foi composta por 30 casos de CE, sendo 10 de assoalho bucal, 10 da regi?o retromolar e 10 de l?ngua, al?m de 10 casos de granuloma piog?nico, integrantes do grupo controle. Os resultados desta pesquisa mostraram que as m?dias da MVC foram correspondentemente mais elevadas no grupo do granuloma piog?nico (CD105 = 57,26 vasos e FvW = 39,64) do que no grupo do CE (CD105 = 10,09 e FvW = 12,20) e as diferen?as se revelaram estatisticamente significantes entre os grupos para cada um dos biomarcadores angiog?nicos (p=0,002 para o CD105 e p<0,001 para o FvW ). O CD105 se mostrou com melhor positividade no granuloma piog?nico (m?dia = 57,26 vasos) e, para o CE, o FvW foi o que apresentou maior marca??o (m?dia = 12,20 vasos). Com rela??o ao CE, a faixa et?ria mais acometida foi entre 51 e 70 anos (n=14; 46,7%), apresentando uma MVC representativa para ambos os marcadores. N?o se comprovou diferen?a estatisticamente significante entre os sexos para nenhum dos marcadores (p=0,967 para o CD105 e p=0,744 para o FvW). A m?dia do CD105 foi bem mais elevada entre os pacientes com estadiamento T3 e T4 (17,13) e menos elevada entre os pacientes com estadiamento N+ (6,36). Quando se avaliou o FvW, a m?dia foi mais elevada no grupo dos pacientes com T1 e T2 (12,23), sendo mais baixa nos pacientes com T3 e T4 (12,10), por?m sem diferen?a estatisticamente significante. Em rela??o ? localiza??o anat?mica, comprovou-se diferen?a estatisticamente significante entre as localiza??es assoalho bucal e retromolar (p=0,013) para o marcador FvW. Portanto, este estudo sugere que a marca??o do CD105 na angiog?nese do CEO, ao contr?rio de outros tipos de neoplasias malignas, pode n?o estar correlacionada com o progn?stico e agressividade do tumor, enquanto que o FvW se mostrou um anticorpo mais efetivo na marca??o desta les?o
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Hegel, Johannes Kolja Eberhard [Verfasser]. "Untersuchung der CD152 vermittelten Regulation der Effektorfunktionen von CD8 T-Lymphozyten / Johannes Kolja Eberhard Hegel." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2008. http://d-nb.info/1023094584/34.
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Liu, Donghui. "The role of CD105 in angiogenesis and its effect on cell signalling and gene expression." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493918.
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Angiogenesis is an invasive cellular process that requires the functional activity of a wide range of molecules including growth factors and their receptors, extracellular metrix proteins, adhesion molecules and proteolytic enzymes. CD 105 is a ISOkDa homodimeric transmembrane glycoprotein expressed at high levels in tumour endothelial cells (ECs) and to a lesser extent in normal ECs. CD 105 is an important component of transforming growth factor-beta (TGF-β) receptor complex and a modulator of TGF-β signalling by interacting with TGF-β receptor I (TβR-I) and/or TGF-β receptor II (TβR-II). CD 105 knockout mice die in utero owing to defective vasculogenesis and angiogenesis. A mutation of CD105 gene in human leads to HHT-1, the suggestion being that CD 105 plays a critical role in angiogenesis.
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Hüttner, Éder Abreu. "Expressão da endoglina (CD105) em carcinomas epidermóide de cavidade oral de pacientes adultos e idosos." Pontifícia Universidade Católica do Rio Grande do Sul, 2006. http://hdl.handle.net/10923/3677.
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Previous issue date: 2006Squamous cell carcinoma (SCC) is the main malignant neoplasy of the oral cavity. The higher incidence of this tumor occurs between the fourth and seventh decade of life, and it has been found a raise in the number of young adults with this pathology in several regions of the world. The aim of this study was to compare anatomopathological characteristics and endoglin expression in the groups of adults (<60 years) and elderly (>/= 60 years). In this study, 27 samples of oral SCC were analisesd. Of the total, 14 specimens were from adult patients and 13 specimens were from elderly patientsThe results showed that a low grade of malignancy, a low pattern of invasion, The clinical, the anatomopathological aspects and the patterns of neoangiogenesis, through the expression of endoglin glycoprotein (CD105) in the groups of adults and elderly, were compared. a high degree of keratinization and a low number of mitosis in the elderly group were statistically significant at (p<0,03, p<0,04, p<0,04, p<0,04, respectively). Neoangiogenesis evaluated through of endoglin expression did not show statistically significant differences in both studied groups. Based on the presented results, in can be concluded that oral SCC of elderly patients show lower grade of malignancy and some anatomopathological characteristics that suggest lower tumoral aggressiveness when compared. However, quantitative alteration of endoglin expression in the analysed groups was not detected.
O carcinoma epidermóide (CEB) é a principal neoplasia maligna da cavidade bucal. A maior incidência desse tumor ocorre entre a quarta e sétima década de vida, sendo que tem sido constatado um aumento no número de adultos jovens com esta patologia em várias regiões do mundo. O objetivo deste estudo foi comparar as características anátomo-patológicas e a expressão da endoglina (CD105) em CEBS dos grupos etários adultos (< 60 anos) e idosos (>/= 60 anos). Foram utilizadas 27 amostras de CEBs, entre as quais 14 espécimens eram oriundas de pacientes adultos e 13 espécimens de pacientes idosos. Foram comparados os aspectos clínicos, anátomopatológicos e os padrões de neoangiogênese, através da expressão da glicoproteína endoglina (CD 105) entre os grupos de adultos e idosos.Os resultados mostraram que a baixa gradação de malignidade, o baixo padrão de invasão, o alto grau de queratinização e o baixo número de mitoses no grupo de idosos foram estatisticamente significantes para (p<0,03), (p<0,04), (p<0,04), (p<0,04), respectivamente, quando comparado com o grupo de adulto a neo-angiogênese avaliada através da quantificação da expressão da endoglina não apresentou diferenças estatisticamente significante para (p<0,05) em ambos grupos estudados. Considerando os resultados apresentados neste estudo, pode-se concluir que os CEBs de pacientes idosos apresentam menor gradação de malignidade e algumas características anátomo-patológicas que sugerem menor agressividade tumoral em relação aos adultos, entretanto, não houve alteração quantitativa da expressão da endoglina entre os grupos analisados.
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Rocha, Andréa Oxley da. "Avaliação imuno-histoquímica da densidade vascular intratumoral com CD105 em espécimes cirúrgicos de vesícula biliar." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2006. http://hdl.handle.net/10183/12934.
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