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Karel Geboes - One of the best experts on this subject based on the ideXlab platform.
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expression of thrombospondin 2 as a marker in proliferative diabetic retinopathy
Acta Ophthalmologica, 2013Co-Authors: Ahmed Abu M Elasrar, Mohd Imtiaz Nawaz, Gert De Hertogh, Ghislain Opdenakker, Karel GeboesAbstract:. Purpose: To determine the expression of the endogenous anti-angiogenic and pro-fibrotic matricellular protein thrombospondin (TSP)-2 and its receptors CD36 and CD47 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of TSP-2 in the retinas of diabetic rats. Methods: Epiretinal membranes from 14 patients with PDR and nine patients with proliferative vitreoretinopathy were studied by immunohistochemistry. Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blotting. Results: In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed TSP-2, CD36 and CD47. In PDR membranes, significant correlations were observed between numbers of blood vessels expressing the panendothelial cell marker CD34 and numbers of blood vessels and stromal cells expressing TSP-2, CD36 and CD47. The numbers of blood vessels and stromal cells expressing CD34, TSP-2, CD36 and CD47 were significantly higher in membranes with active neovascularization when compared with those with quiescent disease. Thrombospondin-2 levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001). Western blot analysis revealed a significant increase in the expression of intact and cleaved TSP-2 in vitreous samples from PDR patients and in the retinas of diabetic rats compared to nondiabetic controls. Conclusions: Upregulation of TSP-2 may be a protective mechanism against inflammation and angiogenesis associated with PDR.
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Expression of thrombospondin-2 as a marker in proliferative diabetic retinopathy
Acta Ophthalmologica, 2013Co-Authors: Ahmed M. Abu El-asrar, Mohd Imtiaz Nawaz, Gert De Hertogh, Ghislain Opdenakker, Karel GeboesAbstract:. Purpose: To determine the expression of the endogenous anti-angiogenic and pro-fibrotic matricellular protein thrombospondin (TSP)-2 and its receptors CD36 and CD47 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of TSP-2 in the retinas of diabetic rats. Methods: Epiretinal membranes from 14 patients with PDR and nine patients with proliferative vitreoretinopathy were studied by immunohistochemistry. Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blotting. Results: In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed TSP-2, CD36 and CD47. In PDR membranes, significant correlations were observed between numbers of blood vessels expressing the panendothelial cell marker CD34 and numbers of blood vessels and stromal cells expressing TSP-2, CD36 and CD47. The numbers of blood vessels and stromal cells expressing CD34, TSP-2, CD36 and CD47 were significantly higher in membranes with active neovascularization when compared with those with quiescent disease. Thrombospondin-2 levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p
Fabio Malavasi - One of the best experts on this subject based on the ideXlab platform.
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cytokine induced killer cells express cd39 cd38 cd203a cd73 ectoenzymes and p1 adenosinergic receptors
Frontiers in Pharmacology, 2018Co-Authors: Alberto L Horenstein, Fabio Malavasi, Antonella Chillemi, Roberta Zini, Valeria Quarona, Nicoletta Bianchi, Rossella Manfredini, Roberto Gambari, Davide FerrariAbstract:Cytokine-induced killer (CIK) cells, a heterogeneous T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC), represent a promising immunological approach in cancer. Numerous studies have explored the role of CD38, CD39, CD203a/PC-1 and CD73 in generating extracellular adenosine (ADO) and thus in shaping the tumor niche in favor of proliferation. The findings shown here reveal that CIK cells are able to produce extracellular ADO via traditional (CD39/CD73) and/or alternative (CD38/CD203a/CD73 or CD203a/CD73) pathways. Transcriptome analysis showed the mRNA expression of these molecules and their modulation during PBMC to CIK differentiation. When PBMC from normal subjects or cancer bearing patients were differentiated into CIK cells under normoxic conditions, CD38 and CD39 were greatly up-regulated while the number of CD203a, and CD73 positive cells underwent minor changes. Since hypoxic conditions are often found in tumors, we asked whether CD39, CD38, CD203a, and CD73 expressed by CIK cells were modulated by hypoxia. PBMC isolated from cancer patients and differentiated into CIK cells in hypoxic conditions did not show relevant changes in CD38, CD39, CD73, CD203a and CD26. CIK cells also expressed A1, A2A, and A2B ADO receptors and they only underwent minor changes as a consequence of hypoxia. The present study sheds light on a previously unknown functional aspect of CIK cells, opening the possibility of pharmacologically modulated ADO-generating ectoezymes to improve CIK cells performance.
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CD38/CD31 Interactions Activate Genetic Pathways Leading to Proliferation and Migration in Chronic Lymphocytic Leukemia Cells
Molecular Medicine, 2010Co-Authors: Silvia Deaglio, Maurizia Mello Grand, Luciana Bergui, Giovanni D’arena, Giovanna Chiorino, Semra Aydin, Tiziana Vaisitti, Fabio MalavasiAbstract:Human CD38 is a pleiotropic glycoprotein belonging to a family of enzymes/receptors involved in the catabolism of extracellular nucleotides. CD38-receptor activities are regulated through binding to the nonsubstrate ligand CD31. CD38 expression above a critical threshold is a negative prognostic marker for chronic lymphocytic leukemia (CLL) patients. Activation of CD38 by means of agonistic monoclonal antibodies or the CD31 ligand induces proliferation and immunoblast differentiation of CLL cells. Here we define the genetic signature that follows long-term in vitro interactions between CD38^+ CLL lymphocytes and CD31^+ cells. The emerging profile confirms that the CD31/CD38 axis activates genetic programs relevant for proliferative responses. It also indicates a contribution of this pathway to the processes mediating migration and homing. These results further support the notion that the CD31/CD38 axis is part of a network of accessory signals that modify the microenvironment, favoring localization of leukemic cells to growth-permissive sites.
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in tandem insight from basic science combined with clinical research cd38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia
Blood, 2006Co-Authors: Silvia Deaglio, Semra Aydin, Tiziana Vaisitti, Enza Ferrero, Fabio MalavasiAbstract:The absence of mutations in the IgV genes, together with the presence of ZAP-70 and CD38, are the most reliable negative prognostic markers for chronic lymphocytic leukemia (CLL) patients. Several lines of evidence indicate that CD38 may be not only a diagnostic marker but also a key element in the pathogenetic network in CLL. First, CD38 is a receptor that induces proliferation and increases survival of CLL cells. Second, CD38 signals start upon interaction with the CD31 ligand expressed by stromal and nurse-like cells. Third, CD38/CD31 contacts up-regulate CD100, a semaphorin involved in sustaining CLL growth. Fourth, evidence that nurselike cells express high levels of CD31 and plexin-B1, the high-affinity ligand for CD100, offers indirect confirmation for this model of receptor cross-talk. Elements of variation in the clinical course of CD38 + CLL patients include (1) potential intersection with ZAP-70, a kinase involved in the CD38 signaling pathway in T and natural killer (NK) cells, and (2) the effects of genetic polymorphisms of the receptors involved, at least of CD38 and CD31 . Consequently, CD38 together with ZAP-70 appear to be the key elements of a coreceptor pathway that may sustain the signals mediated by the B-cell receptor and potentially by chemokines and their receptors. This would result in acquisition of increased survival potential, providing clues to the poorer prognosis of CD38 + patients.
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cd38 and cd100 lead a network of surface receptors relaying positive signals for b cll growth and survival
Blood, 2005Co-Authors: Silvia Deaglio, Luciana Bergui, Alberto L Horenstein, Tiziana Vaisitti, Laurence Boumsell, Lisa Bonello, Luca Tamagnone, Fabio MalavasiAbstract:This work addresses the question whether CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL), plays a role in neoplastic B-cell growth and survival. We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand. The interaction triggers an extensive remodeling of the B-CLL membrane, with relocalization of BCR/CD19 to the CD38/CD31 contact areas, and it also increases cell survival and proliferation. A second event is the up-modulation of the survival receptor CD100, restricted to proliferating cells, and a concomitant decrease of CD72 (low-affinity CD100 ligand and negative regulator of immune responses). The most efficient signals are delivered through sequential interactions between CD38/CD31 and CD100/plexin-B1 (high-affinity CD100 ligand), as inferred by coculture experiments using specific transfectants and blocking monoclonal antibodies (mAbs). The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/CD100+ B-CLL cells, further confirms the model proposed. These findings show that a set of normal receptors and ligands ruling physiologic signaling pathways in B lymphocytes becomes detrimental when expressed in the context of B-CLL cells, ultimately leading to the generation of a tumor reservoir.
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Human myeloma cells express the CD38 ligand CD31
British Journal of Haematology, 1999Co-Authors: Antonella Vallario, Fabio Malavasi, Silvia Deaglio, Marco Chilosi, Fausto Adami, Licia Montagna, Federico Caligaris-cappioAbstract:Multiple myeloma (MM) plasma cells (PC) are CD38+. A ligand for CD38 is the adhesion molecule CD31. By flow cytometry and immunocytochemistry we have investigated whether malignant PC co-express CD38 and CD31. All 68 patients studied were CD38+. 14/14 monoclonal gammopathies of undetermined significance (MGUS) and 39/39 plasmacytic MM patients co-expressed CD38 and CD31 at high density. Only 1/11 plasmablastic MM and 1/4 plasma cell leukaemias (PCL) expressed CD31. These data indicated that PC malignancies co-expressed high levels of both CD38 and its ligand CD31, with the exception of plasmablastic MM and PCL.
A Chaubal - One of the best experts on this subject based on the ideXlab platform.
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endothelial cell markers cd31 cd34 and bnh9 antibody to h and y antigens evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von willebrand factor
Modern Pathology, 1994Co-Authors: Markku Miettinen, A E Lindenmayer, A ChaubalAbstract:: Sixty vascular tumors including 23 angiosarcomas, 300 nonvascular tumors, and selected normal tissues were immunohistochemically evaluated with antibodies to CD31, CD34, and von Willebrand factor (vWF), and monoclonal antibody BNH9, to test the sensitivity and specificity of these markers in the identification of endothelial cells and vascular tumors. Formaldehyde-fixed paraffin-embedded tissues and avidin biotin complex immunostaining were used. All markers labeled normal vascular and lymphatic endothelial cells approximately equally with the exception of CD34 which showed inconsistent expression within the lymphatics. In addition, antibody to CD31 reacted with platelets and megakaryocytes, CD34 with fibroblasts and aortic smooth muscle cells, and BNH9 with many epithelial cells including squamous and gastrointestinal epithelia. Antibody to vWF often showed significant stromal background staining which made the staining occasionally uninterpretable. Benign vascular tumors showed rather uniform staining with all antibodies. However, angiosarcomas were heterogeneous; CD31 was positive in 21/27, CD34 in 25/27 cases, BNH9 in 22/25, and vWF in 18/27 cases. Epithelioid hemangioendotheliomas showed consistent labeling for vWF, but were inconsistently labeled with antibodies to the other markers. Kaposi's sarcoma was positive for both CD31 and CD34. In addition, antibody to CD34 labeled the tumor cells in hemangiopericytoma, cerebellar hemangioblastoma, meningioma, most epithelioid sarcomas, dermatofibrosarcomas, and in a few other sarcomas. CD31, in turn, was not found in sarcomas other than angiosarcomas, but labeled weakly occasional carcinomas and mesotheliomas. Many adenocarcinomas and the glandular component of synovial sarcoma were BNH9 positive.(ABSTRACT TRUNCATED AT 250 WORDS)
Fred T Bosman - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical expression of endothelial markers cd31 cd34 von willebrand factor and fli 1 in normal human tissues
Journal of Histochemistry and Cytochemistry, 2006Co-Authors: Marc Pusztaszeri, Walter Seelentag, Fred T BosmanAbstract:Few systematic studies have been published comparing the expression and distribution of endothelial cell (EC) markers in different vascular beds in normal human tissues. We investigated by immunohistochemistry the expression of CD31, CD34, von Willebrand factor (vWF), and Fli-1 in EC of the major organs and large vessels. Tissue samples obtained from autopsies and biopsy specimens were routinely processed and stained immunohistochemically for CD31, CD34, and vWF. Biopsy material was also stained immunohistochemically for Fli-1, D2-40, and Lyve-1. The expression pattern of the markers was heterogeneous in some of the organs studied. In the kidney, fenestrated endothelium of the glomeruli strongly expressed CD31 and CD34 but was only focally positive or completely negative for vWF. Alveolar wall capillaries of the lung strongly stained for CD31 and CD34 but were usually negative for vWF. The staining intensity for vWF increased gradually with the vessel caliber in the lung. Sinusoids of the spleen and liver...
Silvia Deaglio - One of the best experts on this subject based on the ideXlab platform.
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CD38/CD31 Interactions Activate Genetic Pathways Leading to Proliferation and Migration in Chronic Lymphocytic Leukemia Cells
Molecular Medicine, 2010Co-Authors: Silvia Deaglio, Maurizia Mello Grand, Luciana Bergui, Giovanni D’arena, Giovanna Chiorino, Semra Aydin, Tiziana Vaisitti, Fabio MalavasiAbstract:Human CD38 is a pleiotropic glycoprotein belonging to a family of enzymes/receptors involved in the catabolism of extracellular nucleotides. CD38-receptor activities are regulated through binding to the nonsubstrate ligand CD31. CD38 expression above a critical threshold is a negative prognostic marker for chronic lymphocytic leukemia (CLL) patients. Activation of CD38 by means of agonistic monoclonal antibodies or the CD31 ligand induces proliferation and immunoblast differentiation of CLL cells. Here we define the genetic signature that follows long-term in vitro interactions between CD38^+ CLL lymphocytes and CD31^+ cells. The emerging profile confirms that the CD31/CD38 axis activates genetic programs relevant for proliferative responses. It also indicates a contribution of this pathway to the processes mediating migration and homing. These results further support the notion that the CD31/CD38 axis is part of a network of accessory signals that modify the microenvironment, favoring localization of leukemic cells to growth-permissive sites.
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in tandem insight from basic science combined with clinical research cd38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia
Blood, 2006Co-Authors: Silvia Deaglio, Semra Aydin, Tiziana Vaisitti, Enza Ferrero, Fabio MalavasiAbstract:The absence of mutations in the IgV genes, together with the presence of ZAP-70 and CD38, are the most reliable negative prognostic markers for chronic lymphocytic leukemia (CLL) patients. Several lines of evidence indicate that CD38 may be not only a diagnostic marker but also a key element in the pathogenetic network in CLL. First, CD38 is a receptor that induces proliferation and increases survival of CLL cells. Second, CD38 signals start upon interaction with the CD31 ligand expressed by stromal and nurse-like cells. Third, CD38/CD31 contacts up-regulate CD100, a semaphorin involved in sustaining CLL growth. Fourth, evidence that nurselike cells express high levels of CD31 and plexin-B1, the high-affinity ligand for CD100, offers indirect confirmation for this model of receptor cross-talk. Elements of variation in the clinical course of CD38 + CLL patients include (1) potential intersection with ZAP-70, a kinase involved in the CD38 signaling pathway in T and natural killer (NK) cells, and (2) the effects of genetic polymorphisms of the receptors involved, at least of CD38 and CD31 . Consequently, CD38 together with ZAP-70 appear to be the key elements of a coreceptor pathway that may sustain the signals mediated by the B-cell receptor and potentially by chemokines and their receptors. This would result in acquisition of increased survival potential, providing clues to the poorer prognosis of CD38 + patients.
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cd38 and cd100 lead a network of surface receptors relaying positive signals for b cll growth and survival
Blood, 2005Co-Authors: Silvia Deaglio, Luciana Bergui, Alberto L Horenstein, Tiziana Vaisitti, Laurence Boumsell, Lisa Bonello, Luca Tamagnone, Fabio MalavasiAbstract:This work addresses the question whether CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL), plays a role in neoplastic B-cell growth and survival. We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand. The interaction triggers an extensive remodeling of the B-CLL membrane, with relocalization of BCR/CD19 to the CD38/CD31 contact areas, and it also increases cell survival and proliferation. A second event is the up-modulation of the survival receptor CD100, restricted to proliferating cells, and a concomitant decrease of CD72 (low-affinity CD100 ligand and negative regulator of immune responses). The most efficient signals are delivered through sequential interactions between CD38/CD31 and CD100/plexin-B1 (high-affinity CD100 ligand), as inferred by coculture experiments using specific transfectants and blocking monoclonal antibodies (mAbs). The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/CD100+ B-CLL cells, further confirms the model proposed. These findings show that a set of normal receptors and ligands ruling physiologic signaling pathways in B lymphocytes becomes detrimental when expressed in the context of B-CLL cells, ultimately leading to the generation of a tumor reservoir.
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Human myeloma cells express the CD38 ligand CD31
British Journal of Haematology, 1999Co-Authors: Antonella Vallario, Fabio Malavasi, Silvia Deaglio, Marco Chilosi, Fausto Adami, Licia Montagna, Federico Caligaris-cappioAbstract:Multiple myeloma (MM) plasma cells (PC) are CD38+. A ligand for CD38 is the adhesion molecule CD31. By flow cytometry and immunocytochemistry we have investigated whether malignant PC co-express CD38 and CD31. All 68 patients studied were CD38+. 14/14 monoclonal gammopathies of undetermined significance (MGUS) and 39/39 plasmacytic MM patients co-expressed CD38 and CD31 at high density. Only 1/11 plasmablastic MM and 1/4 plasma cell leukaemias (PCL) expressed CD31. These data indicated that PC malignancies co-expressed high levels of both CD38 and its ligand CD31, with the exception of plasmablastic MM and PCL.
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human cd38 adp ribosyl cyclase is a counter receptor of cd31 an ig superfamily member
Journal of Immunology, 1998Co-Authors: Silvia Deaglio, Massimo Morra, Roberto Mallone, Clara M Ausiello, Elisabeth Prager, G Garbarino, Umberto Dianzani, Hannes Stockinger, Fabio MalavasiAbstract:Human CD38 is a cell surface molecule involved in the regulation of lymphocyte adhesion to endothelial cells. This suggests that HUVEC bear a ligand(s) for CD38 on the cell surface. By means of the mAb Moon-1, which specifically inhibits CD38-mediated cell adhesion, we have identified a trans-membrane 130-kDa molecule acting as a ligand for CD38. Here, we report that the molecule recognized by the Moon-1 mAb is CD31, a member of the Ig superfamily. This conclusion is based on 1) cross-inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2) sequential immunoprecipitation experiments using Moon-1 and known anti-CD31 mAbs, and 3) reactivity of the Moon-1 mAb with CD31 transfectants. Further, CD31 and CD38 cognate interactions were found to modulate heterotypic adhesion as well as to implement cytoplasmic calcium fluxes identical to those obtained by means of agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages for a panel of cytokines, markedly increased upon receptor-ligand interactions. These results suggest that the interplay between CD38 and its ligand CD31 is an important step in the regulation of cell life and of the migration of leukocytes (and CD38+ cancer cells) through the endothelial cell wall.