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Antonella Montinaro

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https://www.readbyqxmd.com/read/30254289/lubac-prevents-lethal-dermatitis-by-inhibiting-cell-death-induced-by-tnf-trail-and-cd95l
#1
Lucia Taraborrelli, Nieves Peltzer, Antonella Montinaro, Sebastian Kupka, Eva Rieser, Torsten Hartwig, Aida Sarr, Maurice Darding, Peter Draber, Tobias L Haas, Ayse Akarca, Teresa Marafioti, Manolis Pasparakis, John Bertin, Peter J Gough, Philippe Bouillet, Andreas Strasser, Martin Leverkus, John Silke, Henning Walczak
The linear ubiquitin chain assembly complex (LUBAC), composed of HOIP, HOIL-1 and SHARPIN, is required for optimal TNF-mediated gene activation and to prevent cell death induced by TNF. Here, we demonstrate that keratinocyte-specific deletion of HOIP or HOIL-1 (E-KO) results in severe dermatitis causing postnatal lethality. We provide genetic and pharmacological evidence that the postnatal lethal dermatitis in HoipE-KO and Hoil-1E-KO mice is caused by TNFR1-induced, caspase-8-mediated apoptosis that occurs independently of the kinase activity of RIPK1...
September 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29695863/lubac-is-essential-for-embryogenesis-by-preventing-cell-death-and-enabling-haematopoiesis
#2
Nieves Peltzer, Maurice Darding, Antonella Montinaro, Peter Draber, Helena Draberova, Sebastian Kupka, Eva Rieser, Amanda Fisher, Ciaran Hutchinson, Lucia Taraborrelli, Torsten Hartwig, Elodie Lafont, Tobias L Haas, Yutaka Shimizu, Charlotta Böiers, Aida Sarr, James Rickard, Silvia Alvarez-Diaz, Michael T Ashworth, Allison Beal, Tariq Enver, John Bertin, William Kaiser, Andreas Strasser, John Silke, Philippe Bouillet, Henning Walczak
The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death2-8 . In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype9-11 ...
May 2018: Nature
https://www.readbyqxmd.com/read/29562199/sterile-inflammation-fuels-gastric-cancer
#3
Antonella Montinaro, Henning Walczak
Constitutively activated NF-κB signaling has long been known to be oncogenic. In this issue of Immunity, O'Reilly et al. (2018) unveil a link between loss of NF-κB1, aberrant STAT1 signaling, sterile inflammation, and the increased expression of immune checkpoint molecules as cancer drivers.
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29345617/loss-of-functional-bap1-augments-sensitivity-to-trail-in-cancer-cells
#4
Krishna Kalyan Kolluri, Constantine Alifrangis, Neelam Kumar, Yuki Ishii, Stacey Price, Magali Michaut, Steven Williams, Syd Barthorpe, Howard Lightfoot, Sara Busacca, Annabel Sharkey, Zhenqiang Yuan, Elizabeth K Sage, Sabarinath Vallath, John Le Quesne, David A Tice, Doraid Alrifai, Sylvia von Karstedt, Antonella Montinaro, Naomi Guppy, David A Waller, Apostolos Nakas, Robert Good, Alan Holmes, Henning Walczak, Dean A Fennell, Mathew Garnett, Francesco Iorio, Lodewyk Wessels, Ultan McDermott, Samuel M Janes
Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15 exome-sequenced MM lines and the discovery of a subset defined by loss of function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). This association is observed across human early passage MM cultures, mouse xenografts and human tumour explants...
January 18, 2018: ELife
https://www.readbyqxmd.com/read/28536452/exploring-the-trails-less-travelled-trail-in-cancer-biology-and-therapy
#5
REVIEW
Silvia von Karstedt, Antonella Montinaro, Henning Walczak
The discovery that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of cancer cells without causing toxicity in mice has led to the in-depth study of pro-apoptotic TRAIL receptor (TRAIL-R) signalling and the development of biotherapeutic drug candidates that activate TRAIL-Rs. The outcome of clinical trials with these TRAIL-R agonists has, however, been disappointing so far. Recent evidence indicates that many cancers, in addition to being TRAIL resistant, use the endogenous TRAIL-TRAIL-R system to their own advantage...
May 24, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28212753/the-trail-induced-cancer-secretome-promotes-a-tumor-supportive-immune-microenvironment-via-ccr2
#6
Torsten Hartwig, Antonella Montinaro, Silvia von Karstedt, Alexandra Sevko, Silvia Surinova, Ankur Chakravarthy, Lucia Taraborrelli, Peter Draber, Elodie Lafont, Frederick Arce Vargas, Mona A El-Bahrawy, Sergio A Quezada, Henning Walczak
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/25843002/cancer-cell-autonomous-trail-r-signaling-promotes-kras-driven-cancer-progression-invasion-and-metastasis
#7
Silvia von Karstedt, Annalisa Conti, Max Nobis, Antonella Montinaro, Torsten Hartwig, Johannes Lemke, Karen Legler, Franka Annewanter, Andrew D Campbell, Lucia Taraborrelli, Anne Grosse-Wilde, Johannes F Coy, Mona A El-Bahrawy, Frank Bergmann, Ronald Koschny, Jens Werner, Tom M Ganten, Thomas Schweiger, Konrad Hoetzenecker, Istvan Kenessey, Balazs Hegedüs, Michael Bergmann, Charlotte Hauser, Jan-Hendrik Egberts, Thomas Becker, Christoph Röcken, Holger Kalthoff, Anna Trauzold, Kurt I Anderson, Owen J Sansom, Henning Walczak
Many cancers harbor oncogenic mutations of KRAS. Effectors mediating cancer progression, invasion, and metastasis in KRAS-mutated cancers are only incompletely understood. Here we identify cancer cell-expressed murine TRAIL-R, whose main function ascribed so far has been the induction of apoptosis as a crucial mediator of KRAS-driven cancer progression, invasion, and metastasis and in vivo Rac-1 activation. Cancer cell-restricted genetic ablation of murine TRAIL-R in autochthonous KRAS-driven models of non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) reduces tumor growth, blunts metastasis, and prolongs survival by inhibiting cancer cell-autonomous migration, proliferation, and invasion...
April 13, 2015: Cancer Cell
https://www.readbyqxmd.com/read/25284787/hoip-deficiency-causes-embryonic-lethality-by-aberrant-tnfr1-mediated-endothelial-cell-death
#8
Nieves Peltzer, Eva Rieser, Lucia Taraborrelli, Peter Draber, Maurice Darding, Barbara Pernaute, Yutaka Shimizu, Aida Sarr, Helena Draberova, Antonella Montinaro, Juan Pedro Martinez-Barbera, John Silke, Tristan A Rodriguez, Henning Walczak
Linear ubiquitination is crucial for innate and adaptive immunity. The linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP, and SHARPIN, is the only known ubiquitin ligase that generates linear ubiquitin linkages. HOIP is the catalytically active LUBAC component. Here, we show that both constitutive and Tie2-Cre-driven HOIP deletion lead to aberrant endothelial cell death, resulting in defective vascularization and embryonic lethality at midgestation. Ablation of tumor necrosis factor receptor 1 (TNFR1) prevents cell death, vascularization defects, and death at midgestation...
October 9, 2014: Cell Reports
https://www.readbyqxmd.com/read/24375678/ubiquitin-in-the-immune-system
#9
REVIEW
Julia Zinngrebe, Antonella Montinaro, Nieves Peltzer, Henning Walczak
Ubiquitination is a post-translational modification process that has been implicated in the regulation of innate and adaptive immune responses. There is increasing evidence that both ubiquitination and its reversal, deubiquitination, play crucial roles not only during the development of the immune system but also in the orchestration of an immune response by ensuring the proper functioning of the different cell types that constitute the immune system. Here, we provide an overview of the latest discoveries in this field and discuss how they impact our understanding of the ubiquitin system in host defence mechanisms as well as self-tolerance...
January 2014: EMBO Reports
https://www.readbyqxmd.com/read/23856527/adenosine-receptors-as-potential-targets-in-melanoma
#10
REVIEW
Antonella Montinaro, Raffaella Iannone, Aldo Pinto, Silvana Morello
Melanoma is one of the most aggressive types of cancer, that is difficult to manage clinically. A major feature of melanoma cells is their ability to escape immune surveillance. Adenosine receptors play a pivotal role in host immune-surveillance. A2a (A2aR) and, partially, A2bR receptors mediate the adenosine-induced immune-suppression, which markedly facilitates tumor development/progression. On the contrary, A3R stimulation enhances the anti-tumor immune response and thus limits tumor growth. A3R also inhibits the proliferation of many cancer cells...
October 2013: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/23059357/the-immunogenicity-and-safety-of-a-single-0-5-ml-dose-of-virosomal-subunit-influenza-vaccine-administered-to-unprimed-children-aged-%C3%A2-6-to-36-months-data-from-a-randomized-phase-iii-study
#11
RANDOMIZED CONTROLLED TRIAL
Susanna Esposito, Paola Marchisio, Valentina Montinaro, Sonia Bianchini, Gerrit Jan Weverling, Elena Pariani, Antonella Amendola, Valentina Fabiano, Valentina Pivetti, Alessandro Zanetti, Gian Vincenzo Zuccotti
This study evaluated the immunogenicity, safety and tolerability of a single 0.5 mL dose of the seasonal virosomal subunit influenza vaccine (Inflexal V, Crucell, Switzerland) in 205 healthy, unprimed children aged at least 6 to <36 months, evaluated at four weeks post-vaccination and seven months from baseline. Of the enrolled children, 102 received one single 0.5 mL dose and 103 received the standard two 0.25 mL doses given four weeks apart. Both treatments evoked an immune response that satisfied the EMA/CHMP criteria for yearly vaccine licensing for all three vaccine strains...
November 19, 2012: Vaccine
https://www.readbyqxmd.com/read/23028986/adoptive-immunotherapy-with-cl-ib-meca-treated-cd8-t-cells-reduces-melanoma-growth-in-mice
#12
Antonella Montinaro, Giovanni Forte, Rosalinda Sorrentino, Antonio Luciano, Giuseppe Palma, Claudio Arra, Ian M Adcock, Aldo Pinto, Silvana Morello
Cl-IB-MECA is a selective A3 adenosine receptor agonist, which plays a crucial role in limiting tumor progression. In mice, Cl-IB-MECA administration enhances the anti-tumor T cell-mediated response. However, little is known about the activity of Cl-IB-MECA on CD8+ T cells. The aim of this study was to investigate the effect of ex vivo Cl-IB-MECA treatment of CD8+ T cells, adoptively transferred in melanoma-bearing mice. Adoptive transfer of Cl-IB-MECA-treated CD8+ T cells or a single administration of Cl-IB-MECA (20 ng/mouse) inhibited tumor growth compared with the control group and significantly improved mouse survival...
2012: PloS One
https://www.readbyqxmd.com/read/22826317/inhibition-of-cd73-improves-b-cell-mediated-anti-tumor-immunity-in-a-mouse-model-of-melanoma
#13
Giovanni Forte, Rosalinda Sorrentino, Antonella Montinaro, Antonio Luciano, Ian M Adcock, Piera Maiolino, Claudio Arra, Carla Cicala, Aldo Pinto, Silvana Morello
CD73 is a cell surface enzyme that suppresses T cell-mediated immune responses by producing extracellular adenosine. Growing evidence suggests that targeting CD73 in cancer may be useful for an effective therapeutic outcome. In this study, we demonstrate that administration of a specific CD73 inhibitor, adenosine 5'-(α,β-methylene)diphosphate (APCP), to melanoma-bearing mice induced a significant tumor regression by promoting the release of Th1- and Th17-associated cytokines in the tumor microenvironment...
September 1, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/21472141/nk1-1-cells-and-cd8-t-cells-mediate-the-antitumor-activity-of-cl-ib-meca-in-a-mouse-melanoma-model
#14
Silvana Morello, Rosalinda Sorrentino, Antonella Montinaro, Antonio Luciano, Piera Maiolino, Anta Ngkelo, Claudio Arra, Ian M Adcock, Aldo Pinto
Cl-IB-MECA, synthetic A(3) adenosine receptor agonist, is a potential anticancer agent. In this study, we have examined the effect of Cl-IB-MECA in a mouse melanoma model. Cl-IB-MECA significantly inhibited tumor growth in immune-competent mice. Notably, the number of tumor-infiltrating NK1.1(+) cells and CD8(+) T cells was significantly increased in Cl-IB-MECA-treated mice. This effect was correlated with high levels of tumor necrosis factor α (TNF-α) and interferon γ in melanoma tissue. Depletion of either CD8(+) T cells or NK1...
April 2011: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/21354814/cl-ib-meca-enhances-tnf-%C3%AE-release-in-peritoneal-macrophages-stimulated-with-lps
#15
Giovanni Forte, Rosalinda Sorrentino, Antonella Montinaro, Aldo Pinto, Silvana Morello
Adenosine receptor A3 (A3R) belongs to the Gi/Gq-coupled receptor family, that leads to the intracellular cAMP reduction and intracellular calcium increase, respectively. A3R is widely expressed and it can play a crucial role in many patho-physiological conditions, including inflammation. Here we investigate the effect of Cl-IB-MECA, A3R agonist, on the production of TNF-α. We found that Cl-IB-MECA enhances LPS-induced TNF-α release in peritoneal macrophages. This effect is reduced by MRS1191, A3R antagonist and by forskolin, activator of adenylyl cyclase...
May 2011: Cytokine
https://www.readbyqxmd.com/read/21278302/b-cells-contribute-to-the-antitumor-activity-of-cpg-oligodeoxynucleotide-in-a-mouse-model-of-metastatic-lung-carcinoma
#16
Rosalinda Sorrentino, Silvana Morello, Giovanni Forte, Antonella Montinaro, Genoveffa De Vita, Antonio Luciano, Giuseppe Palma, Claudio Arra, Piera Maiolino, Ian M Adcock, Aldo Pinto
RATIONALE: CpG-oligodeoxynucleotide (CpG-ODN; CpG), a Toll-like receptor-9 ligand, has been widely studied as a potential antitumor adjuvant. Toll-like receptor-9 is highly expressed on lung carcinoma tissues and some immune cells, such as plasmacytoid dendritic cells and B cells. OBJECTIVES: The aim of our study was to elucidate the effect of CpG on B cells in a mouse model of lung carcinoma. METHODS: C57Bl/6j, B cell-deficient, and Nude mice were intravenously implanted with the lung metastatic B16-F10 melanoma cells and killed 3 and 7 days after CpG administration...
May 15, 2011: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/21127944/retrospective-protein-expression-and-epigenetic-inactivation-studies-of-cdh1-in-patients-affected-by-low-grade-glioma
#17
Pietro Ivo D'Urso, Oscar Fernando D'Urso, Carlo Storelli, Giuseppe Catapano, Cosimo Damiano Gianfreda, Antonio Montinaro, Antonella Muscella, Santo Marsigliante
Aberrant methylation of CpG islands in the promoter regions of tumour cells results in loss of gene function. In addition to genetic lesions, changes in the methylation profile of the promoters may be considered a factor for tumour-specific aberrant expression of the genes.We investigated the methylation status of E-cadherin gene (CDH1) promoter in low-grade glioma and correlated it with clinical outcome. Eighty-four cases of low-grade glioma (43 diffuse astrocytomas, 27 oligodendrogliomas and 14 oligoastrocytomas) with assessable paraffin-embedded tumour blocks and normal brain tissue, derived from non-cancerous tissue adjacent to tumour and commercially normal brain tissue, were collected, from which we determined CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry, respectively...
August 2011: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/17570528/immature-myeloid-and-plasmacytoid-dendritic-cells-infiltrate-renal-tubulointerstitium-in-patients-with-lupus-nephritis
#18
Nicoletta Fiore, Giuseppe Castellano, Antonella Blasi, Carmen Capobianco, Antonia Loverre, Vincenzo Montinaro, Stefano Netti, Diletta Torres, Carlo Manno, Giuseppe Grandaliano, Elena Ranieri, Francesco Paolo Schena, Loreto Gesualdo
Systemic lupus erythematosus (SLE) is an autoimmune disease involving several organs. SLE patients developing lupus nephritis (LN) frequently have the worst outcome. Recent data have shown that dendritic cells (DCs) may have a central role in SLE pathogenesis directing the immune response against auto-antigens. In this study we describe a reduction in circulating BDCA1+ and BDCA3+ myeloid DCs, and BDCA2+ plasmacytoid DCs in patients with active LN compared to those in the remission state. Analysis of LN biopsies revealed a strong tubulo-interstitial infiltrate of BDCA1+, BDCA3+ and BDCA4+ DCs which were negative for DC-LAMP, a specific marker of mature DCs...
January 2008: Molecular Immunology
https://www.readbyqxmd.com/read/12629398/complications-of-pediatric-urological-laparoscopy-mistakes-and-risks
#19
Ciro Esposito, Mario Lima, Girolamo Mattioli, Luciano Mastroianni, Antonella Centonze, Gian Luca Monguzzi, Leonardo Montinaro, Giovanna Riccipetitoni, Alfredo Garzi, Antonio Savanelli, Rocco Damiano, Mario Messina, Alessandro Settimi, Giuseppe Amici, Vincenzo Jasonni, Lane S Palmer
PURPOSE: We evaluate the results and complications of laparoscopic urological procedures in children. MATERIALS AND METHODS: In a 3-year period 4,350 laparoscopic procedures were performed at 8 Italian centers of pediatric surgery. We analyzed only the data of urological procedures for a total of 701 laparoscopic operations on patients 1 month to 14 years old. The indications for surgery were cryptorchidism in 414 cases, varicoceles in 159, ambiguous genitalia in 37, total nephrectomy in 34, partial nephrectomy in 4, adrenalectomy in 3 and other diagnostic procedures in 50...
April 2003: Journal of Urology
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