11 results on '"Antonella Mangoni"'
Search Results
2. HMGB1 attenuates cardiac remodelling in the failing heart via enhanced cardiac regeneration and miR-206-mediated inhibition of TIMP-3.
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Federica Limana, Grazia Esposito, Daniela D'Arcangelo, Anna Di Carlo, Sveva Romani, Guido Melillo, Antonella Mangoni, Chiara Bertolami, Giulio Pompilio, Antonia Germani, and Maurizio C Capogrossi
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Medicine ,Science - Abstract
AIMS: HMGB1 injection into the mouse heart, acutely after myocardial infarction (MI), improves left ventricular (LV) function and prevents remodeling. Here, we examined the effect of HMGB1 in chronically failing hearts. METHODS AND RESULTS: Adult C57 BL16 female mice underwent coronary artery ligation; three weeks later 200 ng HMGB1 or denatured HMGB1 (control) were injected in the peri-infarcted region of mouse failing hearts. Four weeks after treatment, both echocardiography and hemodynamics demonstrated a significant improvement in LV function in HMGB1-treated mice. Further, HMGB1-treated mice exhibited a ∼23% reduction in LV volume, a ∼48% increase in infarcted wall thickness and a ∼14% reduction in collagen deposition. HMGB1 induced cardiac regeneration and, within the infarcted region, it was found a ∼2-fold increase in c-kit⁺ cell number, a ∼13-fold increase in newly formed myocytes and a ∼2-fold increase in arteriole length density. HMGB1 also enhanced MMP2 and MMP9 activity and decreased TIMP-3 levels. Importantly, miR-206 expression 3 days after HMGB1 treatment was 4-5-fold higher than in control hearts and 20-25 fold higher that in sham operated hearts. HMGB1 ability to increase miR-206 was confirmed in vitro, in cardiac fibroblasts. TIMP3 was identified as a potential miR-206 target by TargetScan prediction analysis; further, in cultured cardiac fibroblasts, miR-206 gain- and loss-of-function studies and luciferase reporter assays showed that TIMP3 is a direct target of miR-206. CONCLUSIONS: HMGB1 injected into chronically failing hearts enhanced LV function and attenuated LV remodelling; these effects were associated with cardiac regeneration, increased collagenolytic activity, miR-206 overexpression and miR-206 -mediated inhibition of TIMP-3.
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- 2011
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3. Regression of Human Breast Carcinoma in Nude Mice after Adsflt Gene Therapy Is Mediated by Tumor Vascular Endothelial Cell Apoptosis
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Judith Mühlhauser, Antonella Mangoni, Dieter Marmé, Donald P. Bottaro, Petra Reusch, Young H. Lee, Maurizio C. Capogrossi, Imre Kovesdi, Dinuka M. De Silva, and Angelina Felici
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Cancer Research ,Endothelium ,business.industry ,Genetic enhancement ,Cancer ,medicine.disease ,Vascular endothelial growth factor ,chemistry.chemical_compound ,soluble FLT-1 ,breast carcinoma ,vessel regression ,adenovirus ,gene therapy ,medicine.anatomical_structure ,Oncology ,chemistry ,Apoptosis ,Fibrosis ,In vivo ,embryonic structures ,Cancer research ,medicine ,business ,Receptor - Abstract
Two vascular endothelial growth factor (VEGF) receptors, FLT-1 and KDR, are expressed preferentially in proliferating endothelium. There is increasing evidence that recombinant, soluble VEGF receptor domains interfering with VEGF signaling may inhibit in vivo neoangiogenesis, tumor growth and metastatic spread. We hypothesized that a soluble form of FLT-1 receptor (sFLT-1) could inhibit the growth of pre-established tumors via an anti-angiogenic mechanism. A replication-deficient adenovirus (Ad) vector carrying the sflt-1 cDNA (Adsflt) was used to overexpress the sFLT-1 receptor in a breast cancer animal model. MCF-7 cells, which produce VEGF, were used to establish solid tumors in the mammary fat pads of female nude mice. After six weeks tumors were injected either with Adsflt, or a negative control virus (AdCMV.βgal). After six months, average tumor volume in the Adsflt-infected group (33 ± 22 mm3) was decreased by 91% relative to that of the negative control group (388 ± 94 mm3; Psflt-infected tumors exhibited complete regression. The vascular density in Adsflt-infected tumors was reduced by 50% relative to that of negative controls (Psflt–infected tumors were preceded by apoptosis of tumor vascular endothelial cells. Mice treated with Adsflt intratumorally showed no delay in the healing of cutaneous wounds, providing preliminary evidence that Ad-mediated sFLT-1 overexpression may be an effective anti-angiogenic therapy for cancer without the risk of systemic anti-angiogenic effects.
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- 2022
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4. TRPM7 Is Overexpressed in Human IBD-Related and Sporadic Colorectal Cancer and Correlates with Tumor Grade
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Valentina Trapani, Roberta Benvenuto, Gian Lodovico Rapaccini, Alessandro Armuzzi, Antonio Gasbarrini, Daniela Pugliese, Federica Castri, Luisa Guidi, Federica I. Wolf, and Antonella Mangoni
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Male ,Colorectal cancer ,TRPM6 ,Gene Expression ,TRPM Cation Channels ,Context (language use) ,Inflammation ,colorectal cancer ,Adenocarcinoma ,Protein Serine-Threonine Kinases ,magnesium ,digestive system ,Inflammatory bowel disease ,Malignant transformation ,03 medical and health sciences ,0302 clinical medicine ,TRPM ,inflammatory bowel disease ,Settore MED/04 - PATOLOGIA GENERALE ,medicine ,Humans ,Hepatology ,business.industry ,Gastroenterology ,personalized medicine ,Inflammatory Bowel Diseases ,medicine.disease ,digestive system diseases ,Case-Control Studies ,030220 oncology & carcinogenesis ,sporadic ,Cancer research ,Immunohistochemistry ,Biomarker (medicine) ,biomarker ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Colorectal Neoplasms ,business ,Biomarkers - Abstract
Background Inflammatory bowel disease (IBD) predisposes to colorectal cancer (CRC) with some specific features that distinguish it from sporadic CRC. Magnesium (Mg) homeostasis is severely compromised in IBD patients, which may affect both inflammation and tumor development. Efficient transcellular Mg transport in intestinal cells depends on the transient receptor potential melastatin (TRPM) channels type 6 and 7, but their expression has never been investigated in the context of IBD-related CRC. Aims We sought to study the expression pattern of TRPM6 and TRPM7 in CRC, and to compare IBD-related cases to sporadic cases. Methods TRPM6 and TRPM7 protein expression was evaluated by immunohistochemistry in surgical specimens from 16 IBD and 13 NON-IBD CRC patients. Results TRPM7 expression was higher in tumor tissue than in the adjacent non-neoplastic tissue in both IBD and NON-IBD patients. Overall, adenocarcinomas showed a higher TRPM7 expression than adenomas. TRPM7 expression also positively correlated with tumor grade. Conversely, TRPM6 expression was higher in tumor tissues in both IBD and NON-IBD CRC, but it did not correlate with tumor stage or grade. Conclusions We report a possible participation of TRPM6 and 7 in both IBD-related and sporadic CRC and suggest that TRPM7 might serve as a marker of malignant transformation and lack of differentiation.
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- 2020
5. Molecular mechanisms of cardioprotective effects mediated by transplanted cardiac ckit+cells through the activation of an inflammatory hypoxia-dependent reparative response
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Melissa Manchi, Francesco Facchiano, Laura Pellegrini, Matteo Antonio Russo, Eleonora Foglio, Martina Cordella, Filippo Crea, Antonia Germani, Giovanni Puddighinu, Marco Tafani, Federica Limana, Antonella Mangoni, Elena Pontemezzo, Andrea Siracusano, and Domenico D'Amario
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0301 basic medicine ,030204 cardiovascular system & hematology ,ckit+ stem cells and hypoxia ,ckit+ stem cells and hypoxia, inflammatory and reparative response, myocardial infarction, molecular rehabilitation, cardiac repair ,03 medical and health sciences ,Cardiac repair ,0302 clinical medicine ,Fibrosis ,medicine ,business.industry ,Autophagy ,Inflammatory and reparative response ,Hypoxia (medical) ,medicine.disease ,Molecular rehabilitation ,Transplantation ,Myocardial infarction ,030104 developmental biology ,Ckit+stem cells and hypoxia ,Oncology ,Apoptosis ,Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,Cancer research ,Signal transduction ,medicine.symptom ,Stem cell ,business ,Adult stem cell - Abstract
The regenerative effects of cardiac ckit+ stem cells (ckit+CSCs) in acute myocardial infarction (MI) have been studied extensively, but how these cells exert a protective effect on cardiomyocytes is not well known. Growing evidences suggest that in adult stem cells injury triggers inflammatory signaling pathways which control tissue repair and regeneration. Aim of the present study was to determine the mechanisms underlying the cardioprotective effects of ckit+CSCs following transplantation in a murine model of MI. Following isolation and in vitro expansion, cardiac ckit+CSCs were subjected to normoxic and hypoxic conditions and assessed at different time points. These cells adapted to hypoxia as showed by the activation of HIF-1α and the expression of a number of genes, such as VEGF, GLUT1, EPO, HKII and, importantly, of alarmin receptors, such as RAGE, P2X7R, TLR2 and TLR4. Activation of these receptors determined an NFkB-dependent inflammatory and reparative gene response (IRR). Importantly, hypoxic ckit+CSCs increased the secretion of the survival growth factors IGF-1 and HGF. To verify whether activation of the IRR in a hypoxic microenvironment could exert a beneficial effect in vivo, autologous ckit+CSCs were transplanted into mouse heart following MI. Interestingly, transplantation of ckit+CSCs lowered apoptotic rates and induced autophagy in the peri-infarct area; further, it reduced hypertrophy and fibrosis and, most importantly, improved cardiac function. ckit+CSCs are able to adapt to a hypoxic environment and activate an inflammatory and reparative response that could account, at least in part, for a protective effect on stressed cardiomyocytes following transplantation in the infarcted heart.
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- 2018
6. MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis
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Elisa Gremese, Barbara Tolusso, Luca Petricca, Mariola Kurowska-Stolarska, Gianfranco Ferraccioli, Anna Laura Fedele, Iain B. McInnes, Maria Rita Gigante, S. Canestri, Stefano Alivernini, Clara Di Mario, Aziza Elmesmari, Roberta Benvenuto, and Antonella Mangoni
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0301 basic medicine ,Adult ,Male ,Settore MED/16 - REUMATOLOGIA ,Science ,Population ,General Physics and Astronomy ,Arthritis ,Down-Regulation ,Lymphocyte Activation ,General Biochemistry, Genetics and Molecular Biology ,Article ,Arthritis, Rheumatoid ,03 medical and health sciences ,Proto-Oncogene Proteins ,Synovial Fluid ,medicine ,Humans ,Comorbidities ,Diagnosis algorithm ,Psoriasis ,Psoriatic arthritis ,Rheumatology ,B-cell activating factor ,education ,B cell ,Aged ,miRNA ,education.field_of_study ,B-Lymphocytes ,B cells ,Multidisciplinary ,CD40 ,biology ,business.industry ,Synovial Membrane ,Germinal center ,General Chemistry ,Immunoglobulin D ,Middle Aged ,medicine.disease ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Rheumatoid arthritis ,Immunology ,biology.protein ,Trans-Activators ,Female ,Antibody ,business - Abstract
MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD-CD27- memory B-cell population in ACPA+ RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-α, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA., MiR-155 is thought to inhibit PU.1 and thereby drive antigen-induced B-cell maturation. Here the authors show that patients with rheumatoid arthritis have high B-cell miR-155 expression and that an antagomir can rescue PU.1 expression, suggesting potential therapeutic avenues to treat rheumatoid arthritis.
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- 2016
7. Spontaneous myogenic differentiation of Flk-1-positive cells from adult pancreas and other nonmuscle tissues
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Francesca Pagani, Gabriele Toietta, Maria Grazia Iachininoto, Giuliana Di Rocco, Stefania Straino, Maurizio C. Capogrossi, Ilaria Gatto, Antonella Mangoni, and Alessandra Tritarelli
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Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Myogenic differentiation ,Patch-Clamp Techniques ,Physiology ,Muscle Fibers, Skeletal ,Biology ,Cell Line ,Myoblasts ,Mice ,Fetal Stage ,Internal medicine ,medicine ,Animals ,Muscle, Skeletal ,Pancreas ,Cells, Cultured ,Immunomagnetic Separation ,Myogenesis ,Stem Cells ,Stomach ,Cell Differentiation ,Cell Biology ,Vascular Endothelial Growth Factor Receptor-2 ,Embryonic stem cell ,Clone Cells ,Cell biology ,Endocrinology ,medicine.anatomical_structure ,Gastric Mucosa ,Spleen - Abstract
At the embryonic or fetal stages, autonomously myogenic cells (AMCs), i.e., cells able to spontaneously differentiate into skeletal myotubes, have been identified from several different sites other than skeletal muscle, including the vascular compartment. However, in the adult animal, AMCs from skeletal muscle-devoid tissues have been described in only two cases. One is represented by thymic myoid cells, a restricted population of committed myogenic progenitors of unknown derivation present in the thymic medulla; the other is represented by a small subset of adipose tissue-associated cells, which we recently identified. In the present study we report, for the first time, the presence of spontaneously differentiating myogenic precursors in the pancreas and in other skeletal muscle-devoid organs such as spleen and stomach, as well as in the periaortic tissue of adult mice. Immunomagnetic selection procedures indicate that AMCs derive from Flk-1+progenitors. Individual clones of myogenic cells from nonmuscle organs are morphologically and functionally indistinguishable from skeletal muscle-derived primary myoblasts. Moreover, they can be induced to proliferate in vitro and are able to participate in muscle regeneration in vivo. Thus, we provide evidence that fully competent myogenic progenitors can be derived from the Flk-1+compartment of several adult tissues that are embryologically unrelated to skeletal muscle.
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- 2008
8. High-mobility group box 1 protein in human and murine skin: Involvement in wound healing
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Anna Di Carlo, Stefania Straino, Riccardo Maurelli, Antonia Germani, Fabio Di Giacomo, Marco Bianchi, Roberta Palumbo, Antonella Mangoni, Maurizio C. Capogrossi, Roberta De Mori, Liliana Guerra, Luigi Uccioli, Cristiana Di Campli, Laura Panacchia, Paolo Biglioli, Straino, Stefania, Di Carlo, Anna, Mangoni, Antonella, De Mori, Roberta, Guerra, Liliana, Maurelli, Riccardo, Panacchia, Laura, Di Giacomo, Fabio, Palumbo, Roberta, Di Campli, Cristiana, Uccioli, Luigi, Biglioli, Paolo, Bianchi, MARCO EMILIO, Capogrossi, Maurizio C., and Germani, Antonia
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Keratinocytes ,Pathology ,Epidermi ,Cytoplasm ,medicine.medical_treatment ,Endogeny ,wound healing ,animal cell ,Pharmacology ,wound closure ,Biochemistry ,arteriole ,epidermis cell ,Settore MED/13 - Endocrinologia ,Mice ,Models ,Diabetes Complication ,high mobility group B1 protein ,chemotaxis ,HMGB1 Protein ,granulation tissue ,skin cell ,Skin ,Skin repair ,density ,integumentary system ,biology ,adult ,aged ,animal model ,animal tissue ,article ,cell nucleus ,controlled study ,cytoplasm ,diabetes mellitus ,drug inhibition ,human ,human cell ,human tissue ,in vitro study ,keratinocyte ,male ,mouse ,nonhuman ,priority journal ,protein analysis ,skin ,skin fibroblast ,skin injury ,Animals ,Chemotaxis ,Diabetes Complications ,Epidermis ,Fibroblasts ,Gene Expression Regulation ,Humans ,Inflammation ,Models, Biological ,Wound Healing ,Granulation tissue ,Chemotaxi ,medicine.anatomical_structure ,Cytokine ,Fibroblast ,medicine.symptom ,Keratinocyte ,Human ,medicine.medical_specialty ,chemical and pharmacologic phenomena ,Dermatology ,HMGB1 ,Arteriole ,medicine.artery ,medicine ,Molecular Biology ,business.industry ,Animal ,Cell Biology ,Biological ,Epidermal Cells ,biology.protein ,Wound healing ,business - Abstract
High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory responses and tissue repair. In this study, it was examined whether HMGB1 plays a role in skin wound repair both in normoglycemic and diabetic mice. HMGB1 was detected in the nucleus of skin cells, and accumulated in the cytoplasm of epidermal cells in the wounded skin. Diabetic human and mouse skin showed more reduced HMGB1 levels than their normoglycemic counterparts. Topical application of HMGB1 to the wounds of diabetic mice enhanced arteriole density, granulation tissue deposition, and accelerated wound healing. In contrast, HMGB1 had no effect in normoglycemic mouse skin wounds, where endogenous HMGB1 levels may be adequate for optimal wound closure. Accordingly, inhibition of endogenous HMGB1 impaired wound healing in normal mice but had no effect in diabetic mice. Finally, HMGB1 had a chemotactic effect on skin fibroblasts and keratinoyctes in vitro. In conclusion, lower HMGB1 levels in diabetic skin may play an important role in impaired wound healing and this defect may be overcome by the topical application of HMGB1. © 2008 The Society for Investigative Dermatology.
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- 2008
9. Role of rat α adducin in angiogenesis: Null effect of the F316Y polymorphism
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Patrizia Ferrari, Grazia Tripodi, Roberta Melchionna, Giuseppe Bianchi, Lucia Torielli, Diego Arcelli, Mauro Helmer-Citterich, Maurizio C. Capogrossi, Antonella Mangoni, Monica Napolitano, Claudia Cappuzzello, Cappuzzello, C, Melchionna, R, Mangoni, A, Tripodi, G, Ferrari, P, Torielli, L, Arcelli, D, Helmer Citterich, M, Bianchi, G, Capogrossi, M, and Napolitano, M
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Physiology ,Angiogenesis ,Transcription Factor ,Cellular differentiation ,Fluorescent Antibody Technique ,Gene Expression ,Mice, Inbred Strain ,Umbilical vein ,Mice ,Gene Frequency ,Transduction, Genetic ,Drug Combination ,Intercellular Signaling Peptides and Protein ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis ,Endothelial Cell ,Reverse Transcriptase Polymerase Chain Reaction ,Cell Differentiation ,Hindlimb ,Endothelial stem cell ,Drug Combinations ,Intercellular Signaling Peptides and Proteins ,Proteoglycans ,Collagen ,Cardiology and Cardiovascular Medicine ,Human ,Neovascularization, Physiologic ,Mice, Inbred Strains ,Enzyme-Linked Immunosorbent Assay ,Biology ,In vivo ,Physiology (medical) ,Animals ,Humans ,Cell Proliferation ,Calmodulin-Binding Protein ,Matrigel ,Polymorphism, Genetic ,Animal ,Oligonucleotide Array Sequence Analysi ,Gene Expression Profiling ,Wild type ,Endothelial Cells ,Molecular biology ,In vitro ,Rats ,Proteoglycan ,Rat ,Calmodulin-Binding Proteins ,Laminin ,Transcription Factors - Abstract
Objective: Rat α adducin point mutation (F316Y) has been associated with primary systemic arterial hypertension. As microcirculatory abnormalities are present in most forms of hypertension, the aim of the present study was to investigate whether rat α adducin may regulate endothelial cell (EC) functions in vitro and in vivo. Methods and results: The overexpression of rat wild type α adducin (WT-Add1) in ECs induced capillary-like structure development in Matrigel in vitro and enhanced capillary formation in Matrigel implants in vivo in CD1 mice. In contrast, the overexpression of the mutated form (MUT-Add1) of rat α adducin had a Null effect in vitro and lacked any significant activity in vivo. Further, adenovirus-mediated rat WT-Add1 but not MUT-Add1 gene transfer to murine ischemic hindlimb enhanced capillary formation in skeletal muscles. Gene profiling of human umbilical vein endothelial cells overexpressing α adducin was performed in order to identify putative effector molecules of α adducin-mediated activities on ECs. Interestingly, among a number of genes involved in angiogenesis regulation, retinoic acid-induced protein (RAI17) was found to be upregulated in WT-Add1 vs MUT-Add1 overexpressing cells, possibly representing a key molecule/axis for the functional Add1-induced effect. Conclusions: Rat WT α adducin enhanced EC functions both in vitro and in vivo. The expression of the F316Y variant, associated with the hypertensive phenotype, had a Null effect and might contribute to endothelial rarefaction/dysfunction in hypertension. RAI17 was found to be a putative effector molecule differentially regulated by the overexpression of the two forms of Add1 in endothelial cells. © 2007 European Society of Cardiology.
- Published
- 2007
10. p21(Waf1/Cip1/Sdi1) mediates shear stress-dependent antiapoptotic function
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L. Testolin, Paolo Turrini, Maurizio C. Capogrossi, Stefania Mattiussi, Laura Maria Barlucchi, Annalisa Antonini, Barbara Illi, Carlo Gaetano, Paolo Biglioli, Francesco Osculati, Fabio Martelli, Roberto Testi, Antonella Mangoni, Corrado Cirielli, Chiara Nicolò, Germana Zaccagnini, and Julio Padron
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Male ,Physiology ,Nude ,Inbred Strains ,Apoptosis ,Hindlimb ,Umbilical vein ,chemistry.chemical_compound ,Mice ,Transduction, Genetic ,Ischemia ,Cells, Cultured ,Cultured ,Antiapoptotic Agent ,Sodium nitroprusside ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Cyclin-Dependent Kinase Inhibitor p21 ,Nitroprusside ,Cells ,Genetic Vectors ,Mice, Nude ,Mice, Inbred Strains ,Biology ,Stress ,DNA, Antisense ,Nitric oxide ,Adenoviridae ,Andrology ,Transduction ,Genetic ,In vivo ,Physiology (medical) ,Cyclins ,medicine ,Animals ,Humans ,Nitric Oxide Donors ,Antisense ,Settore MED/04 - Patologia Generale ,Endothelial Cells ,Stress, Mechanical ,DNA ,medicine.disease ,Mechanical ,chemistry ,Immunology - Abstract
Objective: The antiapoptotic effect of p21Waf1/Cip1/Sdi1 (p21) was examined in human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress (SS) or to the nitric oxide donor sodium nitroprusside (SNP) and in a mouse model of hindlimb ischemia. Methods: In vitro: Cells were cultured without serum and in the presence of cobalt chloride to simulate hypoxia for 12 h (T0). Shear stress was applied to endothelial cells for additional 12 h. In vivo: Hindlimb ischemia was realized in mice by femoral artery ligation. SNP was acutely administered by subcutaneous injection or by Alzet osmotic pumps for a longer treatment. Results: At T0, HUVEC were either exposed to SS (15 dyn/cm2/s−1), treated with SNP or kept in static condition (ST) for 1–12 h; after additional 12 h in ST, 30–35% of cells still alive at T0 had died. In this condition, both SS and SNP treatments markedly increased p21 levels and reduced apoptosis in HUVEC. Recombinant adenoviruses carrying p21 (AdCMV.p21) or antisense p21 (AdCMV.ASp21) cDNA revealed that AdCMV.p21-infected HUVEC were protected from death while AdCMV.ASp21 reduced SS- and SNP-dependent protection from apoptosis. In mice, apoptosis was detected in endothelial cells of ischemic hindlimbs as early as 8 h after femoral artery ligation. Treatment with SNP enhanced p21 expression and protected ischemic tissue from damage. Remarkably, direct in vivo injection of AdCMV.p21 significantly reduced the number of apoptotic nuclei in the presence of ischemia. Conclusions: The present study establishes that, under our experimental conditions, (a) p21 plays an important role in SS and nitric oxide antiapoptotic effect in vitro, and (b) p21 gene transfer prevents apoptosis in vitro and in vivo, following acute interruption of blood flow.
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- 2004
11. Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions
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Giulio Bigotti, Manuela M Fabrizi, Guido Massi, Antonella Mangoni, Paola Parente, and Antonella Coli
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Cancer Research ,Pathology ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,Carbohydrate metabolism ,Biology ,lcsh:RC254-282 ,Nevus, Epithelioid and Spindle Cell ,medicine ,Biomarkers, Tumor ,Nevus ,Humans ,Melanoma ,Glucose Transporter Type 1 ,Settore MED/08 - ANATOMIA PATOLOGICA ,Glucose Transporter Type 3 ,Research ,Glucose transporter ,nutritional and metabolic diseases ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Immunohistochemistry ,carbohydrates (lipids) ,Oncology ,Apoptosis ,Cancer cell ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background Reported data indicate that cancer cells have increased rates of glucose metabolism, as determined by 18FDG-PET imaging in patients with malignancies. The results of many studies have demonstrated that the expression of glucose transporters, especially Glut-1, is increased in a variety of malignancies. This study was undertaken to assess the differential expression of Glut-1 and Glut-3 by benign and malignant melanocytic lesions. Methods Immunohistochemical staining for Glut-1 and Glut-3 was performed on paraffin-embedded tissue sections prepared from melanocytic nevi (12 cases), Spitz nevi (12 cases) and primary cutaneous malignant melanomas (20 cases). Results We observed immunoreactivity for Glut-1 in all melanocytic nevi, 9 of the 12 Spitz nevi and in 9 of the 20 malignant melanomas, whereas Glut-3 was expressed in all the melanocytic lesions, both benign and malignant. Conclusion These findings indicate that the glucose transporters Glut-1 and Glut-3 play a role in the glucose metabolism of melanocytic cells. Glut-1 was present in the majority of benign nevi, whereas its expression was downregulated in 55% of malignant melanomas. Our results suggest that glucose transporter Glut-1 expression can significantly discriminate between human malignant melanoma and benign melanocytic nevi, and support the idea that additional mechanisms other than Glut-1 may contribute to glucose uptake in melanomas.
- Published
- 2008
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