المؤلفون: Ardini, Elena, Bosotti, Roberta, Borgia, Andrea Lombardi, De Ponti, Cristina, Somaschini, Alessio, Cammarota, Rosaria, Amboldi, Nadia, Raddrizzani, Laura, Milani, Andrea, Magnaghi, Paola, Ballinari, Dario, Casero, Daniele, Gasparri, Fabio, Banfi, Patrizia, Avanzi, Nilla, Saccardo, Maria B., Alzani, Rachele, Bandiera, Tiziano, Felder, Eduard, Donati, Daniele, Pesenti, Enrico, Sartore-Bianchi, Andrea, Gambacorta, Marcello, Pierotti, Marco A., Siena, Salvatore, Veronese, Silvio, Galvani, Arturo, Isacchi, Antonella

المصدر: Molecular Oncology ; volume 8, issue 8, page 1495-1507 ; ISSN 1574-7891 1878-0261

الوصف: The NTRK1 gene encodes Tropomyosin‐related kinase A (TRKA), the high‐affinity Nerve Growth Factor Receptor. NTRK1 was originally isolated from a colorectal carcinoma (CRC) sample as component of a somatic rearrangement (TPM3‐NTRK1) resulting in expression of the oncogenic chimeric protein TPM3‐TRKA, but there has been no subsequent report regarding the relevance of this oncogene in CRC. The KM12 human CRC cell line expresses the chimeric TPM3‐TRKA protein and is hypersensitive to TRKA kinase inhibition. We report the detailed characterization of the TPM3‐NTRK1 genomic rearrangement in KM12 cells and through a cellular screening approach, the identification of NMS‐P626, a novel highly potent and selective TRKA inhibitor. NMS‐P626 suppressed TPM3‐TRKA phosphorylation and downstream signaling in KM12 cells and showed remarkable antitumor activity in mice bearing KM12 tumors. Finally, using quantitative reverse transcriptase PCR and immunohistochemistry (IHC) we identified the TPM3‐NTRK1 rearrangement in a CRC clinical sample, therefore suggesting that this chromosomal translocation is indeed a low frequency recurring event in CRC and that such patients might benefit from therapy with TRKA kinase inhibitors.

الإتاحة: https://doi.org/10.1016/j.molonc.2014.06.001Test
http://api.elsevier.com/content/article/PII:S1574789114001252?httpAccept=text/xmlTest
http://api.elsevier.com/content/article/PII:S1574789114001252?httpAccept=text/plainTest

المؤلفون: Nicolin, Vanessa, Ponti, Cristina, Narducci, Paola, Grill, Vittorio, Bortul, Roberta, Zweyer, Marina, Vaccarezza, Mauro, Zauli, Giorgio

المصدر: The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology ; volume 286A, issue 2, page 945-954 ; ISSN 1552-4884 1552-4892

الوصف: It has been clearly established that osteoclasts, which play a crucial role in bone resorption, differentiate from hematopoietic cells belonging to the monocyte/macrophage lineage in the presence of macrophage‐colony stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL). We have here investigated the M‐CSF‐ and RANKL‐induced osteoclastic differentiation of two distinct clones of the murine monocytic/macrophagic RAW 264.7 cell line, known as TIB‐71 and CRL‐2278, the latter cell clone being defective for the expression of the inducible nitric oxide synthase isoform in response to interferon‐γ or lipopolysaccharide. CRL‐2278 cells demonstrated a more rapid osteoclastic differentiation than TIB‐71 cells, as documented by morphology, tartrate‐resistant acid phosphatase positivity, and bone resorption activity. The enhanced osteoclastic differentiation of CRL‐2278 was accompanied by a higher rate of cells in the S/G2‐M phases of cell cycle as compared to TIB‐71. The analysis of nitric oxide synthase (NOS) isoforms clearly demonstrated that only neuronal NOS was detectable at high levels in CRL‐2278 but not in TIB cells under all tested conditions. Moreover, the broad inhibitor of NOS activity L‐NAME significantly inhibited osteoclastic differentiation of CRL‐2278 cells. Altogether, these results demonstrate that a basal constitutive neuronal NOS activity positively affects the RANKL/M‐CSF‐related osteoclastic differentiation. © 2005 Wiley‐Liss, Inc.

الإتاحة: https://doi.org/10.1002/ar.a.20239Test

المؤلفون: Vitale, Marco, Bassini, Alessandra, Secchiero, Paola, Mirandola, Prisco, Ponti, Cristina, Zamai, Loris, Mariani, Adriana R., Falconi, Mirella, Azzali, Giacomo

المصدر: The Anatomical Record ; volume 266, issue 2, page 87-92 ; ISSN 0003-276X 1097-0185

الوصف: Natural killer (NK) cell function is largely modulated by growth factors and cytokines. In particular, interleukin (IL)‐2, IL‐12, and IL‐15 have major effects on the proliferative and cytotoxic activities of NK cells against tumor and virus‐infected cells. It is thought that the members of the protein kinase C (PKC) family of serine/threonine kinases play an important role in mediating the pleiotropic effects of cytokines on their target cells. We have investigated the downstream effects generated in purified human NK cells by IL‐2, IL‐12, and IL‐15 on PKCα and PKCϵ—a canonical and a novel isoform of PKC, respectively. By means of Western blotting, PKC activity assays, and immunofluorescence performed on highly purified preparations of primary human NK cells, we demonstrate that: 1) the three cytokines have similar effects on PKCα and PKCϵ activities; 2) whereas PKCϵ activity is induced by cytokine stimulation, PKCα activity is inhibited; and 3) both the induction of PKCϵ and the inhibition of PKCα functional activity are relatively early events in NK cells, while longer cytokine stimulations do not generate significant variations in enzyme activity, suggesting that the activation of both the canonical and novel isoforms of PKC are events required in the early phases of cytokine‐induced NK cell stimulation. Anat Rec 266:87–92, 2002. © 2002 Wiley‐Liss, Inc.

الإتاحة: https://doi.org/10.1002/ar.10039Test

المؤلفون: Ponti, Cristina, Gibellini, Davide, Boin, Francesco, Melloni, Elisabetta, Manzoli, Francesco A., Cocco, Lucio, Zauli, Giorgio, Vitale, Marco

المصدر: European Journal of Immunology ; volume 32, issue 12, page 3358-3365 ; ISSN 0014-2980 1521-4141

الإتاحة: https://doi.org/10.1002/1521-4141Test(2002012)32:12%3C3358::aid-immu3358%3E3.0.co%3B2-8

المؤلفون: Gibellini, Davide, Re, Maria Carla, Ponti, Cristina, Celeghini, Claudio, Melloni, Elisabetta, La Placa, Michele, Zauli, Giorgio

المصدر: British Journal of Haematology ; volume 112, issue 3, page 663-670 ; ISSN 0007-1048 1365-2141

الوصف: The regulatory human immunodeficiency virus‐1 (HIV‐1) Tat protein shows pleiotropic effects on the survival and growth of both HIV‐1‐infected and uninfected CD4 + T lymphocytes. In this study, we have demonstrated that low concentrations (10 ng/ml) of extracellular Tat protein induce the expression of both c‐fos mRNA and protein in serum‐starved Jurkat CD4 + lymphoblastoid T cells. Using deletion mutants, we demonstrates that the SRE, CRE and, to a lesser extent, also the SIE domains (all placed in the first 356 bp of c‐fos promoter) play a key role in mediating the response to extracellular Tat. Moreover, the ability of Tat to activate the transcriptional activity of c‐fos promoter was consistently decreased by pretreatment with the ERK/MAPK kinase inhibitor PD98058. Activation of c‐fos is functional as demonstrated by induction of the AP‐1 transcription factor, which is involved in the regulation of critical genes for the activation of T lymphocytes, such as interleukin 2. The Tat‐mediated induction of c‐fos and AP‐1 in uninfected lymphoid T cells may contribute to explain the immune hyperactivation that characterizes the progression to autoimmuno deficiency syndrome and constitutes the optimal environment for HIV‐1 replication, occurring predominantly in activated/proliferating CD4 + T cells.

الإتاحة: https://doi.org/10.1046/j.1365-2141.2001.02576.xTest

المؤلفون: Piccaluga, Pier Paolo, Agostinelli, Claudio, Righi, Simona, Ciccone, Maria, Re, Maria Carla, Musumeci, Giuseppina, Diani, Erica, Signoretto, Caterina, Bon, Isabella, Piccin, Ottavio, Cuneo, Antonio, Tripodo, Claudio, Ponti, Cristina, Zipeto, Donato, Landolfo, Santo, Gibellini, Davide

المساهمون: Associazione Italiana per la Ricerca sul Cancro

المصدر: APMIS ; volume 125, issue 6, page 511-522 ; ISSN 0903-4641 1600-0463

الوصف: Chronic lymphocytic leukemia ( CLL ) is the most common leukemia in adults. Its clinical course is typically indolent; however, based on a series of pathobiological, clinical, genetic, and phenotypic parameters, patient survival varies from less than 5 to more than 20 years. In this paper, we show for the first time that the expression of the interferon‐inducible DNA sensor IFI 16, a member of the PYHIN protein family involved in proliferation inhibition and apoptosis regulation, is associated with the clinical outcome in CLL . We studied 99 CLL s cases by immunohistochemistry and 10 CLL s cases by gene expression profiling. We found quite variable degrees of IFI 16 expression among CLL s cases. Noteworthy, we observed that a reduced IFI 16 expression was associated with a very poor survival, but only in cases with ZAP 70/ CD 38 expression. Furthermore, we found that IFI 16 expression was associated with a specific gene expression signature. As IFI 16 can be easily detected by immunohistochemistry or flow cytometry, it may become a part of phenotypic screening in CLL patients if its prognostic role is confirmed in independent series.

الإتاحة: https://doi.org/10.1111/apm.12692Test

المؤلفون: Arshad Fiaz, Muhammad, Frezza, Fabrizio, Pajewski, Lara, Ponti, Cristina, Schettini, Giuseppe

المصدر: Near Surface Geophysics ; volume 13, issue 3, page 219-225 ; ISSN 1569-4445 1873-0604

الوصف: An analytical‐numerical approach in the spectral domain is developed for the scattering problem by buried objects excited by a two‐dimensional illumination field. The scatterers are perfectly conducting cylinders, which are placed in a semi‐infinite medium below a flat interface. The source field is described by an arbitrary illumination function, and it is represented by means of its plane‐wave spectrum. The cylindrical‐wave approach is applied to represent the fields scattered by the cylinders. All the field contributions are expressed through spectral integrals, which allow to evaluate their interaction with the interface in terms of a superposition of monochromatic plane waves. Such integrals are evaluated in an accurate way, which can lead to results both in near‐field and far‐field regions. In this paper, the general theoretical approach is described, and numerical results are given for the case of an incident Gaussian beam. Two‐dimensional field maps in both the air and lower regions are reported in the case of one and two scatterers. An application of the technique to the diagnostic of reinforced concrete is reported, showing the use of the radar scattering cross‐section ratio to determine the size of rebar diameters. Modelling results validate the assumption proposed by other authors that the radar scattering cross‐section ratio can be used to determine rebar diameters using the monotonic behaviour observed at lower frequencies.

الإتاحة: https://doi.org/10.3997/1873-0604.2015022Test

المؤلفون: Gibellini, Davide, Miserocchi, Anna, Tazzari, Pier Luigi, Ricci, Francesca, Clò, Alberto, Morini, Silvia, Ponti, Cristina, Pasquinelli, Gianandrea, Bon, Isabella, Pagliaro, Pasqualepaolo, Borderi, Marco, Re, Maria Carla

المصدر: Journal of Cellular Biochemistry ; volume 113, issue 4, page 1132-1141 ; ISSN 0730-2312 1097-4644

الوصف: HIV infection is an independent risk factor for atherosclerosis development and cardiovascular damage. As vessel wall mesenchymal stem cells (MSCs) are involved in the regulation of vessel structure homeostasis, we investigated the role of Tat, a key factor in HIV replication and pathogenesis, in MSC survival and differentiation. The survival of subconfluent MSCs was impaired when Tat was added at high concentrations (200–1,000 ng/ml), whereas lower Tat concentrations (1–100 ng/ml) did not promote apoptosis. Tat enhanced the differentiation of MSC toward adipogenesis by the transcription and activity upregulation of PPARγ. This Tat‐related modulation of adipogenesis was tackled by treatment with antagonists of Tat‐specific receptors such as SU5416 and RGD Fc. In contrast, Tat inhibited the differentiation of MSCs to endothelial cells by downregulating the expression of VEGF‐induced endothelial markers such as Flt‐1, KDR, and vWF. The treatment of MSCs with Tat‐derived peptides corresponding to the cysteine‐rich, basic, and RGD domains indicated that these Tat regions are involved in the inhibition of endothelial marker expression. The Tat‐related impairment of MSC survival and differentiation might play an important role in vessel damage and formation of the atherosclerotic lesions observed in HIV‐infected patients. J. Cell. Biochem. 113: 1132–1141, 2012. © 2011 Wiley Periodicals, Inc.

الإتاحة: https://doi.org/10.1002/jcb.23446Test

المؤلفون: Frezza, Fabrizio, Pajewski, Lara, Ponti, Cristina, Schettini, Giuseppe

المصدر: Microwave and Optical Technology Letters ; volume 51, issue 11, page 2769-2774 ; ISSN 0895-2477 1098-2760

الوصف: In this article, a design of both high‐selectivity and compact one‐dimensional electromagnetic band‐gap (1D‐EBG) cavities is presented, considering the effect of the layers' thickness and of the permittivity of the constitutive materials. Compact and high‐selectivity cavities are proposed, to be employed as spatial filters. In particular, EBG antennas can be obtained when the ground plane of a patch antenna is placed in the symmetry plane of these cavities. An effect of enlargement of the equivalent‐aperture area is determined, resulting in high‐gain radiation. © 2009 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 2769–2774, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24737

الإتاحة: https://doi.org/10.1002/mop.24737Test

المؤلفون: Gibellini, Davide, De Crignis, Elisa, Ponti, Cristina, Cimatti, Laura, Borderi, Marco, Tschon, Matilde, Giardino, Roberto, Re, Maria Carla

المصدر: Journal of Medical Virology ; volume 80, issue 9, page 1507-1514 ; ISSN 0146-6615 1096-9071

الوصف: Several HIV‐1 infected patients show bone loss and osteopenia/osteoporosis during the course of disease. The mechanisms underlying this degenerative process are largely unsettled and it has not been determined yet whether bone dysfunction is linked to HIV‐1‐mediated direct and/or indirect effects on osteoblasts/osteoclasts cross‐talk regulation. This study investigated the effects of HIV‐1 IIIb and HIV‐1 ADA strains on osteoblasts using the osteoblast‐derived cell line (HOBIT) and primary human osteoblasts as cellular models. The challenge of these cell cultures by both HIV‐1 strains triggered a significant apoptosis activation unrelated to viral infection, since proviral HIV‐1 DNA and supernatant HIV‐1 RNA were not detected by real time PCR or b‐DNA assays respectively. Under the experimental conditions, even heat‐inactivated HIV‐1 or cross‐linked recombinant gp120 treatment of HOBIT and osteoblasts induced programmed cell death, suggesting that apoptosis is regulated by the interaction between HIV‐1 gp120 and cell membrane. The analysis of cell culture supernatants showed a significant up‐regulation of TNFα, a pleiotropic protein considered an apoptosis inducer in the osteoblast model. In fact, pretreatment of HOBIT and osteoblast cell cultures with anti‐TNFα polyclonal antibody tackled effectively HIV‐1 related induction of cell apoptosis. As a whole, these results indicate that HIV‐1 may impair bone mass structure homeostasis by TNFα regulated osteoblast apoptosis. J. Med. Virol. 80:1507–1514, 2008. © 2008 Wiley‐Liss, Inc.

الإتاحة: https://doi.org/10.1002/jmv.21266Test