58 results on '"Vincenzo Dattilo"'
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2. Clinical validation of a combinatorial PharmAcogeNomic approach in major Depressive disorder: an Observational prospective RAndomized, participant and rater-blinded, controlled trial (PANDORA trial)
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Alessandra Minelli, Stefano Barlati, Erika Vitali, Stefano Bignotti, Vincenzo Dattilo, Giovanni Battista Tura, Elisabetta Maffioletti, Edoardo Giacopuzzi, Vincenza Santoro, Giulia Perusi, Chiara Cobelli, Chiara Magri, Silvia Bonizzato, Luisella Bocchio-Chiavetto, Edoardo Spina, Antonio Vita, and Massimo Gennarelli
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Major depressive disorder ,Depression ,Pharmacogenetic testing ,Randomized controlled clinical ,Precision medicine ,Antidepressant response ,Medicine (General) ,R5-920 - Abstract
Abstract Background Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence. Methods Our study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their current treatment and/or the onset of adverse effects. Eligible participants are randomized to the TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, DNA is collected with a buccal brush. The primary outcome is the reduction in depressive symptomatology. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks. Discussion This project represents the first randomized controlled clinical trial to investigate whether a non-commercial PGx test improves outcomes in an MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test, leading to further cost-saving. Trial registration number ClinicalTrials.gov NCT04615234. Registered on November 4, 2020.
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- 2021
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3. LRRK2 Kinase Inhibition Attenuates Astrocytic Activation in Response to Amyloid β1-42 Fibrils
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Alice Filippini, Valentina Salvi, Vincenzo Dattilo, Chiara Magri, Stefania Castrezzati, Robert Veerhuis, Daniela Bosisio, Massimo Gennarelli, and Isabella Russo
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LRRK2 ,Alzheimer’s disease ,astrocytes ,amyloid-β ,neuroinflammation ,Microbiology ,QR1-502 - Abstract
Intracerebral accumulation of amyloid-β in the extracellular plaques of Alzheimer’s disease (AD) brains represents the main cause of reactive astrogliosis and neuroinflammatory response. Of relevance, leucine-rich repeat kinase 2 (LRRK2), a kinase linked to genetic and sporadic Parkinson’s disease (PD), has been identified as a positive mediator of neuroinflammation upon different inflammatory stimuli, however its pathogenicity in AD remains mainly unexplored. In this study, by using pharmacological inhibition of LRRK2 and murine primary astrocytes, we explored whether LRRK2 regulates astrocytic activation in response to amyloid-β1-42 (Aβ1-42). Our results showed that murine primary astrocytes become reactive and recruit serine 935 phosphorylated LRRK2 upon Aβ1-42 fibril exposure. Moreover, we found that pharmacological inhibition of LRRK2, with two different kinase inhibitors, can attenuate Aβ1-42-mediated inflammation and favor the clearance of Aβ1-42 fibrils in astrocytes. Overall, our findings report that LRRK2 kinase activity modulates astrocytic reactivity and functions in the presence of Aβ1-42 deposits and indicate that PD-linked LRRK2 might contribute to AD-related neuroinflammation and pathogenesis.
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- 2023
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4. Predominant VH1-69 IgBCR Clones Show Higher Expression of CD5 in Heterogeneous Chronic Lymphocytic Leukemia Populations
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Domenico Maisano, Enrico Iaccino, Alessandro D’Ambrosio, Federico Chiurazzi, Vincenzo Dattilo, Mariangela Scalise, Massimo Gentile, Eleonora Vecchio, Nancy Nisticò, Annamaria Aloisio, Erika De Sensi, Giuseppe Fiume, Ileana Quinto, and Selena Mimmi
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chronic lymphocytic leukemia ,phage display ,immunoglobulin B cell receptor ,peptide-based sorting ,gene expression ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The immunoglobulin B cell receptor (IgBCR) expressed by chronic lymphocytic leukemia (CLL) B cells plays a pivotal role in tumorigenesis, supporting neoplastic transformation, survival, and expansion of tumor clones. We demonstrated that in the same patient, two or more CLL clones could coexist, recognized by the expression of different variable regions of the heavy chain of IgBCR, composing the antigen-binding site. In this regard, phage display screening could be considered the easier and most advantageous methodology for the identification of small peptide molecules able to mimic the natural antigen of the tumor IgBCRs. These molecules, properly functionalized, could be used as a probe to specifically identify and isolate single CLL subpopulations, for a deeper analysis in terms of drug resistance, phenotype, and gene expression. Furthermore, CLL cells express another surface membrane receptor, the CD5, which is commonly expressed by normal T cells. Piece of evidence supports a possible contribution of CD5 to the selection and maintenance of autoreactivity in B cells and the constitutive expression of CD5 on CLL cells could induce pro-survival stimuli. In this brief research report, we describe a peptide-based single-cell sorting using as bait the IgBCR of tumor cells; in the next step, we performed a quantitative analysis of CD5 expression by qRT-PCR related to the expressed IgBCR. Our approach could open a new perspective for the identification, isolation, and investigation of all subsets of IgBCR-related CLL clones, with particular attention to the more aggressive clones.
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- 2021
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5. In Preclinical Model of Ovarian Cancer, the SGK1 Inhibitor SI113 Counteracts the Development of Paclitaxel Resistance and Restores Drug Sensitivity
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Lucia D'Antona, Vincenzo Dattilo, Giada Catalogna, Domenica Scumaci, Claudia Vincenza Fiumara, Francesca Musumeci, Giuseppe Perrotti, Silvia Schenone, Rossana Tallerico, Cristina B. Spoleti, Nicola Costa, Rodolfo Iuliano, Giovanni Cuda, Rosario Amato, and Nicola Perrotti
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Ovarian cancer is the second most common gynecological malignancy worldwide. Paclitaxel is particularly important in the therapy of ovarian carcinomas, but the treatment efficacy is counteracted by the development of resistance to chemotherapy. The identification of target molecules that can prevent or control the development of chemoresistance might provide important tools for the management of patients affected by ovarian cancer. Serum- and glucocorticoid-regulated kinase 1 (SGK1) appears to be a key determinant of resistance to chemo- and radiotherapy. Specifically, SGK1 affects paclitaxel sensitivity in RKO colon carcinoma cells by modulating the specificity protein 1 (SP1)–dependent expression of Ran-specific GTPase-activating protein (RANBP1), a member of the GTP-binding nuclear protein Ran (RAN) network that is required for the organization and function of the mitotic spindle. SGK1 inhibition might thus be useful for counteracting the development of paclitaxel resistance. Here, we present in vitro data obtained using ovarian carcinoma cell lines that indicate that the SGK1 inhibitor SI113 inhibits cancer cell proliferation, potentiates the effects of paclitaxel-based chemotherapy, counteracts the development of paclitaxel resistance, and restores paclitaxel sensitivity in paclitaxel-resistant A2780 ovarian cancer cells. The results were corroborated by preclinical studies of xenografts generated in nude mice through the implantation of paclitaxel-resistant human ovarian cancer cells. The SGK1 inhibitor SI113 synergizes with paclitaxel in the treatment of xenografted ovarian cancer cells. Taken together, these data suggest that SGK1 inhibition should be investigated in clinical trials for the treatment of paclitaxel-resistant ovarian cancer.
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- 2019
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6. Th17-Gene Expression Profile in Patients with Chronic Venous Disease and Venous Ulcers: Genetic Modulations and Preliminary Clinical Evidence
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Rosario Amato, Vincenzo Dattilo, Carolina Brescia, Lucia D’Antona, Rodolfo Iuliano, Francesco Trapasso, Nicola Perrotti, Davide Costa, Nicola Ielapi, Francesco Aiello, Michele Provenzano, Umberto Marcello Bracale, Michele Andreucci, and Raffaele Serra
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chronic venous insufficiency ,chronic venous leg ulcers ,Th17 ,SGK1 ,IL17 ,IL23R ,Microbiology ,QR1-502 - Abstract
Chronic venous disease is a condition globally widespread, resulting in a disabling pathological disorder. The CD4 + Th17+ (Cluster Differentiation 4) lymphocytes represent a regulative factor for innate immunity related to the development of complex diseases. Recently, these mechanisms have been associated with vascular disease. The aim of this work is to validate whether the Th17 response correlates with the development of CVI (Chronic venous insufficiency)and CVLUs (chronic venous limbs ulcers) and whether Th17 markers can be used, both as intrinsic risk factors and diagnostic markers, for disease development. PBL derived from peripheral blood samples of patients and controls were subjected to gene expression analysis for IL23R, IL17, SGK1, TGFβ, RORγ, FOXO1, and RANBP1 by qRT-PCR and immunoblot. A post hoc correlation, the diagnostic performance of the target genes, and multivariable analyses were properly conducted. The main expression markers of the CD4 + Th17+ switch were strongly activated in chronic venous insufficiency and in advanced ulceration. The correlation analysis demonstrated the inter-dependence on Th17’s signature modulation. ROC (Receiver Operating Characteristic) analysis defined, for the examined genes, a clinical value as the potential diagnostic markers. Multi-logistic regression studies showed that Th17 markers behave as empirical risk factors for CVD (chronic venous disease) development. Taken together, the present data provide a new hypothesis for the TH17-dependent pathogenesis of CVD, favoring the possibility for the development of new diagnostic, preventive, and therapeutic approaches.
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- 2022
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7. Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo
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Rich Abbott, Thomas D. Abbott, Sheelu Abraham, Fausto Acernese, Kendall Ackley, Carl Adams, Rana X. Adhikari, Vaishali B. Adya, Christoph Affeldt, Michalis Agathos, Kazuhiro Agatsuma, Nancy Aggarwal, Odylio D. Aguiar, Amit Aich, Lorenzo Aiello, Anirban Ain, Ajith Parameswaran, Gabrielle Allen, Annalisa Allocca, Paul A. Altin, Alex Amato, Shreya Anand, Alena Ananyeva, Stuart B. Anderson, Warren G. Anderson, Svetoslava V. Angelova, Stefano Ansoldi, Sarah Antier, Stephen Appert, Koji Arai, Melody C. Araya, Joseph S. Areeda, Marc Arène, Nicolas Arnaud, Scott M. Aronson, Kg G. Arun, Stefano Ascenzi, Gregory Ashton, Stuart M. Aston, Pia Astone, Florian Aubin, Peter Aufmuth, Kellie AultONeal, Corey Austin, Valerie Avendano, Stanislav Babak, Philippe Bacon, Francesca Badaracco, Maria K.M. Bader, Sangwook Bae, Anne M. Baer, Jonathon Baird, Francesca Baldaccini, Giulio Ballardin, Stefan W. Ballmer, Anna-marie Bals, Alexander Balsamo, Gregory Baltus, Sharan Banagiri, Deepak Bankar, Rameshwar S. Bankar, Juan C. Barayoga, Claudio Barbieri, Barry C. Barish, David Barker, Kevin Barkett, Pablo Barneo, Fabrizio Barone, Bryan Barr, Lisa Barsotti, Matteo Barsuglia, Daniel Barta, Jeffrey Bartlett, Imre Bartos, Riccardo Bassiri, Andrea Basti, Mateusz Bawaj, Joseph C. Bayley, Marco Bazzan, Bence Bécsy, Michal Bejger, Imene Belahcene, Angus S. Bell, Deeksha Beniwal, Michael G. Benjamin, Joe D. Bentley, Fabio Bergamin, Beverly K. Berger, Gerald Bergmann, Sebastiano Bernuzzi, Christopher P.L. Berry, Diego Bersanetti, Alessandro Bertolini, Joseph Betzwieser, Rohan Bhandare, Ankit V. Bhandari, Jeffrey Bidler, Edward Biggs, Igor A. Bilenko, Garilynn Billingsley, Ross Birney, Ofek Birnholtz, Sebastien Biscans, Matteo Bischi, Sylvia Biscoveanu, Aparna Bisht, Guldauren Bissenbayeva, Massimiliano Bitossi, Marieanne A. Bizouard, Kent K. Blackburn, Jonathan Blackman, Carl D. Blair, David G. Blair, Ryan M. Blair, Fabrizio Bobba, Nina Bode, Michel Boer, Yannick Boetzel, Gilles Bogaert, Francois Bondu, Edgard Bonilla, Romain Bonnand, Phillip Booker, Boris A. Boom, Rolf Bork, Valerio Boschi, Sukanta Bose, Vladimir Bossilkov, Joel Bosveld, Yann Bouffanais, Antonella Bozzi, Carlo Bradaschia, Patrick R. Brady, Alyssa Bramley, Marica Branchesi, Jim E. Brau, Matteo Breschi, Tristan Briant, Joseph H. Briggs, Francesco Brighenti, Alain Brillet, Marc Brinkmann, Patrick Brockill, Aidan F. Brooks, Jonathan Brooks, Daniel D. Brown, Sharon Brunett, Giacomo Bruno, Robert Bruntz, Aaron Buikema, Tomasz Bulik, Henk J. Bulten, Alessandra Buonanno, Damir Buskulic, Robert L. Byer, Miriam Cabero, Laura Cadonati, Giampietro Cagnoli, Craig Cahillane, Juan Calderón Bustillo, Jack D. Callaghan, Thomas A. Callister, Enrico Calloni, Jordan B. Camp, Maurizio Canepa, Kipp C. Cannon, Huy-tuong Cao, Junwei Cao, Giovanni Carapella, Franco Carbognani, Santiago Caride, Matthew F. Carney, Gregorio Carullo, Julia Casanueva Diaz, Claudio Casentini, Javier Castañeda, Sarah Caudill, Marco Cavaglià, Fabien Cavalier, Roberto Cavalieri, Giancarlo Cella, Pablo Cerdá-Durán, Elisabetta Cesarini, Oualid Chaibi, Kabir Chakravarti, Chiwai Chan, Manleong Chan, Shiuh Chao, Philip Charlton, Eve A. Chase, Eric Chassande-Mottin, Deep Chatterjee, Mayank Chaturvedi, Hsin-yu Y. Chen, Xu Chen, Yanbei Chen, Hai-ping Cheng, Chi-kit K. Cheong, Hanyu Y. Chia, Francesco Chiadini, Roberto Chierici, Andrea Chincarini, Antonino Chiummo, Gihyuk Cho, Heesuk S. Cho, Min-a Cho, Nelson Christensen, Qi Chu, Sheon Chua, Ka-wai W. Chung, Shinkee Chung, Giacomo Ciani, Pawel Ciecielag, Marek Cieślar, Alexei A. Ciobanu, Riccardo Ciolfi, Francesco Cipriano, Alessio Cirone, Filiberto Clara, James A. Clark, Patrick Clearwater, Sebastien Clesse, Frederic Cleva, Eugenio Coccia, Pierre-francois Cohadon, David Cohen, Marta Colleoni, Christophe G. Collette, Christopher Collins, Monica Colpi, Marcio Constancio Jr., Livia Conti, Sam J. Cooper, Paul Corban, Thomas R. Corbitt, Isabel Cordero-Carrión, Silvia Corezzi, Kenneth R. Corley, Neil Cornish, David Corre, Alessandra Corsi, Stefano Cortese, Cesar A. Costa, Roberto Cotesta, Michael W. Coughlin, Scott B. Coughlin, Jeanpierre Coulon, Stefan T. Countryman, Peter Couvares, Pep B. Covas, David M. Coward, Matthew J. Cowart, Dennis C. Coyne, Robert Coyne, Jolien D. E. Creighton, Teviet D. Creighton, Jonathan Cripe, Michael Croquette, Sgwynne G. Crowder, Jean-rene Cudell, Torrey J. Cullen, Alan Cumming, Rebecca Cummings, Liam Cunningham, Elena Cuoco, Malgorzata Curylo, Tito Dal Canton, Gergely Dálya, Aykutlu Dana, Lara M. Daneshgaran-Bajastani, Beatrice D’Angelo, Stefan L. Danilishin, Sabrina D’Antonio, Karsten Danzmann, Christian Darsow-Fromm, Arnab Dasgupta, Laurence E. H. Datrier, Vincenzo Dattilo, Ishant Dave, Michel Davier, Gareth S. Davies, Derek Davis, Edward J. Daw, Dan DeBra, Malathi Deenadayalan, Jerome Degallaix, Martina De Laurentis, Samuel Deléglise, Matthew Delfavero, Nicola De Lillo, Walter Del Pozzo, Lindsay M. DeMarchi, Virginia D’Emilio, Nicholas Demos, Thomas Dent, Roberto De Pietri, Rosario De Rosa, Camilla De Rossi, Riccardo DeSalvo, Omar de Varona, Sanjeev Dhurandhar, Mario C. Díaz, Mauricio Diaz-Ortiz Jr., Tim Dietrich, Luciano Di Fiore, Chiara Di Fronzo, Cinzia Di Giorgio, Fabrizio Di Giovanni, Matteo Di Giovanni, Tristano Di Girolamo, Alberto Di Lieto, Binlei Ding, Sibilla Di Pace, Irene Di Palma, Francesco Di Renzo, Atul K. Divakarla, Artemiy Dmitriev, Zoheyr Doctor, Fred Donovan, Katherine L. Dooley, Suresh Doravari, Iain Dorrington, Thomas P. Downes, Marco Drago, Jenne C. Driggers, Zhihui Du, Jean-gregoire Ducoin, Peter Dupej, Ofelia Durante, Domenico D’Urso, Sheila E. Dwyer, Paul J. Easter, Graeme Eddolls, Bruce Edelman, Tega B. Edo, Oliver Edy, Anamaria Effler, Phil Ehrens, Johannes Eichholz, Stephen S. Eikenberry, Marc Eisenmann, Robert A. Eisenstein, Aldo Ejlli, Lucianolucianikerrico Errico, Reed C. Essick, Hector Estelles, Dimitri Estevez, Zachariah B. Etienne, Todd Etzel, Matthew Evans, Tom M. Evans, Rebecca E. Ewing, Viviana Fafone, Stephen Fairhurst, Xilong Fan, Stefania Farinon, Benjamin Farr, Will M. Farr, Edward J. Fauchon-Jones, Marc Favata, Maxime Fays, Mariana Fazio, Jon Feicht, Martin M. Fejer, Fangchen Feng, Edit Fenyvesi, Deborah L. Ferguson, Alvaro Fernandez-Galiana, Isidoro Ferrante, Elvis C. Ferreira, Tabata A. Ferreira, Francesco Fidecaro, Irene Fiori, Donatella Fiorucci, Maya Fishbach, Ryan P. Fisher, Rosalba Fittipaldi, Margot Fitz-Axen, Vincenzo Fiumara, Raffaele Flaminio, Erik Floden, Eric Flynn, Heather Fong, Antonio A. Font, Perry Forsyth, Jean-daniel Fournier, Sergio Frasca, Franco Frasconi, Zsolt Frei, Andreas Freise, Raymond Frey, Valentin Frey, Peter Fritschel, Valery V. Frolov, Gabriele Fronzè, Paul Fulda, Michael Fyffe, Hunter A. Gabbard, Bhooshan U. Gadre, Sebastian M. Gaebel, Jonathan R. Gair, Shanika Galaudage, Dhruva Ganapathy, Sharad G. Gaonkar, Cecilio García-Quirós, Fabio Garufi, Bubba Gateley, Sergio Gaudio, Gayathri Gayathri, Gianluca Gemme, Eric Genin, Alberto Gennai, Daniel George, Jogy George, Laszlo Gergely, Sudarshan Ghonge, Abhirup Ghosh, Archisman Ghosh, Shaon Ghosh, Bruno Giacomazzo, Joe A. Giaime, Dwayne D. Giardina, Des R. Gibson, Chalisa Gier, Kiranjyot Gill, Jane Glanzer, Jan Gniesmer, Patrick Godwin, Evan Goetz, Ryan Goetz, Niklas Gohlke, Boris Goncharov, Gabriela González, Gopakumar Gopakumar, Sarah E. Gossan, Matthieu Gosselin, Romain Gouaty, Benjamin Grace, Aniello Grado, Massimo Granata, Alastair Grant, Slawomir Gras, Philippe Grassia, Corey Gray, Rachel Gray, Giuseppe Greco, Anna C. Green, Rhys Green, Elizabeth M. Gretarsson, Hannah L. Griggs, G. Grignani, Andrea Grimaldi, Stefan J. Grimm, Hartmut Grote, Steffen Grunewald, Pierre Gruning, Gianluca M. Guidi, Andre R. Guimaraes, Gerard Guixé, Hitesh K. Gulati, Yuefan Guo, Anuradha Gupta, Anchal Gupta, Pawan Gupta, Eric K. Gustafson, Dick Gustafson, Leila Haegel, Odysse Halim, Evan D. Hall, Eleanor Z. Hamilton, Giles Hammond, Maria Haney, Manuela M. Hanke, Jonathan Hanks, Chad Hanna, Mark D. Hannam, Otto A. Hannuksela, Travis J. Hansen, Joe Hanson, Thomas Harder, Terra Hardwick, Haris Haris, Jan Harms, Gregg M. Harry, Ian W. Harry, Raine K. Hasskew, Carl-johan Haster, Karen Haughian, Fergus J. Hayes, James Healy, Antoine Heidmann, Matthew C. Heintze, Joscha Heinze, Henrich Heitmann, Frances Hellman, Patrice Hello, Gary Hemming, Martin Hendry, Siong S. Heng, Eric Hennes, Jan-simon Hennig, Michele Heurs, Stefan Hild, Tanja Hinderer, Sarah Y. Hoback, Sven Hochheim, Elyssa Hofgard, David Hofman, Aaron M. Holgado, Nathan A. Holland, Kathy Holt, Daniel E. Holz, Paul Hopkins, Christian Horst, James Hough, Eric J. Howell, Charlie G. Hoy, Yiwen Huang, Moritz T. Hübner, Eliu A. Huerta, Dominique Huet, Brennan Hughey, Victor Hui, Sascha Husa, Sabina H. Huttner, Rachael Huxford, Tien Huynh-Dinh, Bartosz Idzkowski, Alberto Iess, Henri Inchauspe, Craig Ingram, Giuseppe Intini, Jean M. Isac, Max Isi, Bala R. Iyer, Thibaut Jacqmin, Sameer J. Jadhav, Shreejit P. Jadhav, Alasdair L. James, Karan Jani, Nagaraj N. Janthalur, Piotr Jaranowski, Deep Jariwala, Rafel Jaume, Alex C. Jenkins, Jun Jiang, Grace R. Johns, Aaron W. Jones, Ian I. Jones, Jeff D. Jones, Philip Jones, Russell Jones, Reinier J. G. Jonker, Ju Ju, Jonas Junker, Chinmay V. Kalaghatgi, Vassiliki Kalogera, Brittany Kamai, Shivaraj Kandhasamy, Gungwon Kang, Jonah B. Kanner, Shasvath J. Kapadia, Sudarshan Karki, Rahul Kashyap, Marie Kasprzack, Wolfgang Kastaun, Stavros Katsanevas, Erik Katsavounidis, William Katzman, Steffen Kaufer, Keita Kawabe, Fabien Kéfélian, David Keitel, Azadeh Keivani, Ross Kennedy, Joey S. Key, Sudiksha Khadka, Farit Y. Khalili, Imran Khan, Sebastian Khan, Zaki A. Khan, Efim A. Khazanov, Nandita Khetan, Mohammad Khursheed, Nutsinee Kijbunchoo, Chunglee Kim, Grace J. Kim, Jeongcho C. Kim, Kyungmin Kim, Won Kim, Whansun S. Kim, Young-min Kim, Charles Kimball, Peter J. King, Maya Kinley-Hanlon, Robin Kirchhoff, Jeffrey S. Kissel, Lisa Kleybolte, Sergei Klimenko, Tyler D. Knowles, Philip Koch, Sina M. Koehlenbeck, Gideon Koekoek, Soumen Koley, Veronica Kondrashov, Antonios Kontos, Nico Koper, Mikhail Korobko, William Z. Korth, Manoj Kovalam, Dan B. Kozak, Volker Kringel, Nv V. Krishnendu, Andrzej Królak, Natalie Krupinski, Gerrit Kuehn, Anil Kumar, Prayush Kumar, Rahul Kumar, Rakesh Kumar, Sumit Kumar, Ling-chi Kuo, Adam Kutynia, Benjamin D. Lackey, Danny Laghi, Emile Lalande, Lam L. Lam, Astrid Lamberts, Michael Landry, Benjamin B. Lane, Ryan N. Lang, Jacob Lange, Brian Lantz, Robert K. Lanza, Iuri La Rosa, Angelique Lartaux-Vollard, Paul D. Lasky, Michael Laxen, Albert Lazzarini, Claudia Lazzaro, Paola Leaci, Sean Leavey, Yannick K. Lecoeuche, Chang-hwan H. Lee, Hyung-mok M. Lee, Hyungwon W. Lee, Joongoo Lee, Kyung-ha Lee, Johannes Lehmann, Nicolas Leroy, Nicolas Letendre, Yuri Levin, Alvin K. Y. Li, Jin Li, Kaye li, Tjonnie G. F. Li, Xiang Li, Frank Linde, Seth D. Linker, Jethro N. Linley, Tyson B. Littenberg, Liu Liu, Xiaoshu Liu, Miquel Llorens-Monteagudo, Ka-lok Lo, Alexandra Lockwood, Lionel T. London, Alessandro Longo, Matteo Lorenzini, Vincent Loriette, Marc Lormand, Giovanni Losurdo, James D. Lough, Carlos O. Lousto, Geoffrey Lovelace, Harald Lück, Diana Lumaca, Andrew P. Lundgren, Ma Yiqiu, Ronaldas Macas, Sean Macfoy, Myron MacInnis, Duncan M. Macleod, Ian O. MacMillan, Adrian Macquet, Ignacio Magaña Hernandez, Fabian Magaña-Sandoval, Ryan M. Magee, Ettore Majorana, Ivan Maksimovic, Asmita Malik, Catherine Man, Vuk Mandic, Valentina Mangano, Georgia L. Mansell, Michael Manske, Maddalena Mantovani, Michela Mapelli, Fabio Marchesoni, Frederique Marion, Szabolcs Márka, Zsuzsanna Márka, Charalampos Markakis, Ashot S. Markosyan, Aaron Markowitz, Ed Maros, Antonio Marquina, Sylvain Marsat, Filippo Martelli, Ian W. Martin, Rodica M. Martin, Valerie Martinez, Denis V. Martynov, Hossein Masalehdan, Ken Mason, Elena Massera, Alain Masserot, Thomas J. Massinger, Mariela Masso-Reid, Simone Mastrogiovanni, Andrew Matas, Fabrice Matichard, Nergis Mavalvala, Emily Maynard, Joshua J. McCann, Richard McCarthy, David E. McClelland, Scott McCormick, Lee McCuller, Stephen C. McGuire, Connor McIsaac, Jessica McIver, David J. McManus, Terry McRae, Sean T. McWilliams, Duncan Meacher, Grant D. Meadors, Moritz Mehmet, Ajit K. Mehta, Elena Mejuto Villa, Andrew Melatos, Gregory Mendell, Adam A. Mercer, Lorenzo Mereni, Kara Merfeld, Edmond L. Merilh, Jonathan D. Merritt, Mourad Merzougui, Syd Meshkov, Chris Messenger, Cody Messick, Remi Metzdorff, Patrick M. Meyers, Fabian Meylahn, Ashish Mhaske, Andrea Miani, Haixing Miao, Ioannis Michaloliakos, Christophe Michel, Hannah Middleton, Leopoldo Milano, Andrewlawrence L. Miller, Meg Millhouse, Joseph C. Mills, Edoardo Milotti, Michael C. Milovich-Goff, Olivier Minazzoli, Yuri Minenkov, Alec Mishkin, Chandra Mishra, Timesh Mistry, Sanjit Mitra, Valery P. Mitrofanov, Guenakh Mitselmakher, Richard Mittleman, Geoffrey Mo, Kentaro Mogushi, Satyanarayan R. P. Mohapatra, Siddharth R. Mohite, Manel Molina-Ruiz, Marina Mondin, Matteo Montani, Christopher J. Moore, Dan Moraru, Filip Morawski, Gerardo Moreno, Soichiro Morisaki, Benoit Mours, Conor M. Mow-Lowry, Simone Mozzon, Federico Muciaccia, Arunava Mukherjee, Debnandini Mukherjee, Soma Mukherjee, Subroto Mukherjee, Nikhil Mukund, Adam Mullavey, Jesper Munch, Erik A. Muñiz, Peter G. Murray, Alessandro Nagar, Ilaria Nardecchia, Luca Naticchioni, Rajesh K. Nayak, Benjamin F. Neil, Joshua Neilson, Gijs Nelemans, Timothy J. N. Nelson, Marina Nery, Ansel Neunzert, Kwan-yeung Y. Ng, Sebastian Ng, Catherine Nguyen, Philippe Nguyen, David Nichols, Shania A. Nichols, Samaya Nissanke, Flavio Nocera, Minkyun Noh, Chris North, Devon Nothard, Laura K. Nuttall, Jason Oberling, Brendan D. O’Brien, Gor Oganesyan, Greg H. Ogin, John J. Oh, Sanghoon H. Oh, Frank Ohme, Hiroaki Ohta, Marcos A. Okada, Miquel Oliver, Christian Olivetto, Patrick Oppermann, Richard Oram, Brian O’Reilly, Rich G. Ormiston, Luis F. Ortega, Richard O’Shaughnessy, Serguei Ossokine, Charles Osthelder, David J. Ottaway, Harry Overmier, Ben J. Owen, Alexander E. Pace, Giulia Pagano, Michael A. Page, Giulia Pagliaroli, Archana Pai, Siddhesh A. Pai, Jordan R. Palamos, Oleg Palashov, Cristiano Palomba, Howard Pan, Pratap K. Panda, Tsun-ho Pang, Chris Pankow, Francesco Pannarale, Brijesh C. Pant, Federico Paoletti, Andrea Paoli, Abhishek Parida, William Parker, Daniela Pascucci, Antonio Pasqualetti, Roberto Passaquieti, Diego Passuello, Barbara Patricelli, Ethan Payne, Brynley L. Pearlstone, Thida C. Pechsiri, Ari J. Pedersen, Mike Pedraza, Arnaud Pele, Steven Penn, Albino Perego, Carlos J. Perez, Perigois Périgois, Antonio Perreca, Stephane Perriès, Jan Petermann, Harald P. Pfeiffer, Margot Phelps, Khun S. Phukon, Ornella J. Piccinni, Mikhael Pichot, Marco Piendibene, Francesco Piergiovanni, Vincenzo Pierro, Gabriel Pillant, Laurent Pinard, Innocenzo M. Pinto, Krzysztof Piotrzkowski, Marc Pirello, Matthew Pitkin, Wolfango Plastino, Rosa Poggiani, Yat-tung T. Pong, Sarah Ponrathnam, Pasquale Popolizio, Ed K. Porter, Jade Powell, Atul K. Prajapati, Kiran Prasai, Raghurama Prasanna, Geraint Pratten, Tanner Prestegard, Maria Principe, Giovanni A. Prodi, Leonid Prokhorov, Michele Punturo, Paola Puppo, Michael Pürrer, Hong Qi, Volker Quetschke, Pedro J. Quinonez, Fred J. Raab, Geert Raaijmakers, Hugh Radkins, Nicholas Radulesco, Peter Raffai, Hanna Rafferty, Sendhil Raja, Rajan Rajan, Binod Rajbhandari, Malik Rakhmanov, Karla E. Ramirez, Antoni Ramos-Buades, Javed Rana, Kaushik Rao, Piero Rapagnani, Vivien Raymond, Massimiliano Razzano, Jocelyn Read, Tania Regimbau, Luca Rei, Stuart Reid, David H. Reitze, Piero Rettegno, Fulvio Ricci, Colter J. Richardson, Jonathan W. Richardson, Paul M. Ricker, Gunnar Riemenschneider, Keith Riles, Monica Rizzo, Norna A. Robertson, Florent Robinet, Alessio Rocchi, Ramon D. Rodriguez-Soto, Loic Rolland, Jameson G. Rollins, Vincent J. Roma, Marco Romanelli, Rocco Romano, Chandra L. Romel, Isobel M. Romero-Shaw, Janeen H. Romie, Caitlin A. Rose, Dakota Rose, Kyle Rose, Dorota Rosińska, Shawn G. Rosofsky, Michael P. Ross, Sheila Rowan, Samuel J. Rowlinson, Palash K. Roy, Santosh Roy, Soumen Roy, Paolo Ruggi, Guntis Rutins, Kyle Ryan, Surabhi Sachdev, Travis Sadecki, Mairi Sakellariadou, Om S. Salafia, Livio Salconi, Muhammed Saleem, Anuradha Samajdar, Eduardo J. Sanchez, Luis E. Sanchez, Nicolas Sanchis-Gual, Jaclyn R. Sanders, Kevin A. Santiago, Edison Santos, Nikhil Sarin, Benoit Sassolas, B S. Sathyaprakash, Orion Sauter, Richard L. Savage, Vaibhav Savant, Disha Sawant, Sihem Sayah, Dean Schaetzl, Paul Schale, Mark Scheel, Jacob Scheuer, Patricia Schmidt, Roman Schnabel, Robert M. S. Schofield, Axel Schönbeck, Emil Schreiber, Bernd W. Schulte, Bernard F. Schutz, Otto Schwarm, Eyal Schwartz, Jamie Scott, Susan M. Scott, Ed Seidel, Danny Sellers, Anand S. Sengupta, Noah Sennett, Daniel Sentenac, Valeria Sequino, Alexander Sergeev, Yoshinta Setyawati, Daniel A. Shaddock, Thomas Shaffer, Selim S. Shahriar, A. Sharma, Priyanka Sharma, Peter Shawhan, Hongyu Shen, Minori Shikauchi, Rosalie Shink, David H. Shoemaker, Deirdre M. Shoemaker, Keerti Shukla, Shyamsundar ShyamSundar, Karelle Siellez, Magdalena Sieniawska, Daniel Sigg, Leo P. Singer, Divya Singh, Neha Singh, Ayatri Singha, Akshat Singhal, Alicia M. Sintes, Valeria Sipala, Vasileios Skliris, Bram J. J. Slagmolen, Teresa J. Slaven-Blair, Jiri Smetana, Joshua R. Smith, Rory J. E. Smith, Surendranadh Somala, Edwin J. Son, Siddharth Soni, Borja Sorazu, Viola Sordini, Fiodor Sorrentino, Tarun Souradeep, Eric Sowell, Andrew P. Spencer, Mario Spera, Amit K. Srivastava, Varun Srivastava, Kai Staats, Cosmin Stachie, Mark Standke, Daniele A. Steer, Michael Steinke, Jessica Steinlechner, Sebastian Steinlechner, Daniel Steinmeyer, Dane Stocks, David J. Stops, Madeline Stover, Ken A. Strain, Giulia Stratta, Amber Strunk, Riccardo Sturani, Amber L. Stuver, Sudhagar Sudhagar, Vivishek Sudhir, Tiffany Z. Summerscales, Ling Sun, Sunil Sunil, Ankan Sur, Jishnu Suresh, Patrick J. Sutton, Bas L. Swinkels, Marek J. Szczepańczyk, Matteo Tacca, Simon C. Tait, Colm Talbot, Andres J. Tanasijczuk, David B. Tanner, Duo Tao, Marton Tápai, Amauri Tapia, Enzo N. Tapia San Martin, Jay D. Tasson, Robert Taylor, Rodrigo Tenorio, Lukas Terkowski, Manasadevi P. Thirugnanasambandam, Michael Thomas, Patrick Thomas, Jonathan E. Thompson, Sivananda R. Thondapu, Keith A. Thorne, Eric Thrane, Calley L. Tinsman, Saravanan R. Saravanan, Shubhanshu Tiwari, Srishti Tiwari, Vaibhav Tiwari, Karl Toland, Mauro Tonelli, Zeno Tornasi, Alejandro Torres-Forné, Calum I. Torrie, Iara Tosta e Melo, Daniel Töyrä, Emily A. Trail, Flavio Travasso, Gary Traylor, Maria C. Tringali, Aashish Tripathee, Agata Trovato, Randy J. Trudeau, Ka-wa W. Tsang, Maggie Tse, Rhondale Tso, Leo Tsukada, Daichi Tsuna, Takuya Tsutsui, Margherita Turconi, Amit S. Ubhi, Koh Ueno, Dennis Ugolini, Cs S. Unnikrishnan, Alexander L. Urban, Samantha A. Usman, Andrei C. Utina, Henning Vahlbruch, Gabriele Vajente, Guillermo Valdes, Michele Valentini, M. Vallisneri, Niels van Bakel, Martin van Beuzekom, Jo F. J. van den Brand, Chris Van Den Broeck, Daniel C. Vander-Hyde, Laura van der Schaaf, Joris V. Van Heijningen, Marielle A. van Veggel, Marco Vardaro, Vijay Varma, Steve Vass, Matyas Vasúth, Alberto Vecchio, Gabriele Vedovato, John Veitch, Peter J. Veitch, Krishna Venkateswara, Gautam Venugopalan, Didier Verkindt, Doga Veske, Flavio Vetrano, Andrea Viceré, Aaron D. Viets, Serena Vinciguerra, David J. Vine, Jeanyves Vinet, Salvatore Vitale, Francisco Hernandez Vivanco, Thomas Vo, Helios Vocca, Cheryl Vorvick, Sergey P. Vyatchanin, Andrew R. Wade, Leslie E. Wade, Madeline Wade, Rob Walet, Marissa Walker, Gavin S. Wallace, Larry Wallace, Sinead Walsh, Jonathan Z. Wang, Sibo Wang, Wenhui H. Wang, Yifan F. Wang, Robert L. Ward, Zane A. Warden, Jim Warner, Michal Was, Jennifer Watchi, Betsy Weaver, Li-wei Wei, Michael Weinert, Alan J. Weinstein, Rainer Weiss, Felix Wellmann, Linqing Wen, Peter Weßels, Jonathan W. Westhouse, Karl Wette, John T. Whelan, Bernard F. Whiting, Chris Whittle, Dennis M. Wilken, Daniel Williams, Roy D. Williams, Andrew R. Williamson, Joshua L. Willis, Benno Willke, Walter Winkler, Christopher C. Wipf, Holger Wittel, Graham Woan, Janis Woehler, Jared K. Wofford, Chun-fung Wong, Jennifer L. Wright, David S. Wu, Daniel M. Wysocki, Liting Xiao, Hiro Yamamoto, Le Yang, Yang Yang, Ziyan Yang, Min-jet J. Yap, Maher Yazback, David W. Yeeles, Hang Yu, Haocun Yu, Shingheirobin Yuen, Adam K. Zadrożny, Adam Zadrożny, Michele Zanolin, Tatiana Zelenova, Jean-pierre Zendri, Michael Zevin, Jue Zhang, Liyuan Zhang, Teng Zhang, Chunnong Zhao, Guoying Zhao, Minchuan Zhou, Zifan Zhou, Xingjiang J. Zhu, Aaron B. Zimmerman, Michael E. Zucker, and John Zweizig
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GWOSC ,Scientific databases ,Data representation and management ,Gravitational Waves ,Computer software ,QA76.75-76.765 - Abstract
Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.
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- 2021
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8. Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay
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Selena Mimmi, Domenico Maisano, Vincenzo Dattilo, Massimo Gentile, Federico Chiurazzi, Alessandro D’Ambrosio, Annamaria Zimbo, Nancy Nisticò, Annamaria Aloisio, Eleonora Vecchio, Giuseppe Fiume, Enrico Iaccino, and Ileana Quinto
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B-cells ,chronic lymphocytic leukemia ,gene expression analysis ,CLL heterogeneity ,B-lymphoproliferative disorders ,phage display ,Biology (General) ,QH301-705.5 - Abstract
Chronic Lymphocytic Leukemia (CLL) is a heterogeneous disease characterized by variable clinical courses among different patients. This notion was supported by the possible coexistence of two or more independent CLL clones within the same patients, identified by the characterization of the B cell receptor immunoglobulin (BcR IG) idiotypic sequence. By using the antigen-binding site of the BcR IG as bait, the identification and isolation of aggressive and drug-resistance leukemic B-cell clones could allow a deeper biological and molecular investigation. Indeed, by the screening of phage display libraries, we previously selected a peptide binder of the idiotypic region of CLL BCR IGs expressing the unmutated rearrangement IGHV1-69 and used it as a probe to perform a peptide-based cell sorting by flow cytometry in peripheral blood samples from patients with CLL. Since the IGHV1-69 clones persisted during the follow-up time in both patients, we explored the possibility of these clones having acquired an evolutive advantage compared to the other coexisting clones in terms of a higher expression of genes involved in the survival and apoptosis escape processes. To this end, we studied the expression patterns of a panel of genes involved in apoptosis regulation and in NF-kB-dependent pro-survival signals by comparative qRT-PCR assays. According to the results, IGHV1-69 clones showed a higher expression of pro-survival and anti-apoptotic genes as compared to the other CLL clones with different immunogenetic characteristics. Moreover, these IGHV1-69 clones did not carry any characteristic genetic lesions, indicating the relevance of our approach in performing a comprehensive molecular characterization of single tumor clones, as well as for designing new personalized therapeutic approaches for the most aggressive and persistent tumor clones.
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- 2022
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9. The Emerging Role of SGK1 (Serum- and Glucocorticoid-Regulated Kinase 1) in Major Depressive Disorder: Hypothesis and Mechanisms
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Vincenzo Dattilo, Rosario Amato, Nicola Perrotti, and Massimo Gennarelli
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major depressive disorder ,SGK1 ,neurodevelopment ,stress ,inflammation ,neurotrophins ,Genetics ,QH426-470 - Abstract
Major depressive disorder (MDD) is a heterogeneous psychiatric disease characterized by persistent low mood, diminished interests, and impaired cognitive and social functions. The multifactorial etiology of MDD is still largely unknown because of the complex genetic and environmental interactions involved. Therefore, no established mechanism can explain all the aspects of the disease. In this light, an extensive research about the pathophysiology of MDD has been carried out. Several pathogenic hypotheses, such as monoamines deficiency and neurobiological alterations in the stress-responsive system, including the hypothalamic–pituitary–adrenal (HPA) axis and the immune system, have been proposed for MDD. Over time, remarkable studies, mainly on preclinical rodent models, linked the serum- and glucocorticoid-regulated kinase 1 (SGK1) to the main features of MDD. SGK1 is a serine/threonine kinase belonging to the AGK Kinase family. SGK1 is ubiquitously expressed, which plays a pivotal role in the hormonal regulation of several ion channels, carriers, pumps, and transcription factors or regulators. SGK1 expression is modulated by cell stress and hormones, including gluco- and mineralocorticoids. Compelling evidence suggests that increased SGK1 expression or function is related to the pathogenic stress hypothesis of major depression. Therefore, the first part of the present review highlights the putative role of SGK1 as a critical mediator in the dysregulation of the HPA axis, observed under chronic stress conditions, and its controversial role in the neuroinflammation as well. The second part depicts the negative regulation exerted by SGK1 in the expression of both the brain-derived neurotrophic factor (BDNF) and the vascular endothelial growth factor (VEGF), resulting in an anti-neurogenic activity. Finally, the review focuses on the antidepressant-like effects of anti-oxidative nutraceuticals in several preclinical model of depression, resulting from the restoration of the physiological expression and/or activity of SGK1, which leads to an increase in neurogenesis. In summary, the purpose of this review is a systematic analysis of literature depicting SGK1 as molecular junction of the complex mechanisms underlying the MDD in an effort to suggest the kinase as a potential biomarker and strategic target in modern molecular antidepressant therapy.
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- 2020
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10. Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes
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Enrico Iaccino, Selena Mimmi, Vincenzo Dattilo, Fabiola Marino, Patrizio Candeloro, Antonio Di Loria, Danilo Marimpietri, Antonio Pisano, Francesco Albano, Eleonora Vecchio, Simona Ceglia, Gaetanina Golino, Antonio Lupia, Giuseppe Fiume, Ileana Quinto, and Giuseppe Scala
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression.
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- 2017
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11. The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells
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Giada Catalogna, Cristina Talarico, Vincenzo Dattilo, Vincenzo Gangemi, Ferdinando Calabria, Lucia D’Antona, Silvia Schenone, Francesca Musumeci, Cataldo Bianco, Nicola Perrotti, Rosario Amato, and Giuseppe L. Cascini
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SGK1 ,GBM ,64CuCl2 ,SI113 ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Background/Aims: The importance of copper in the metabolism of cancer cells has been widely studied in the last 20 years and a clear-cut association between copper levels and cancer deregulation has been established. Copper-64, emitting positrons and β-radiations, is indicated for the labeling of a large number of molecules suitable for radionuclide imaging as well as radionuclide therapy. Glioblastoma multiforme (GBM) is the CNS tumor with the worse prognosis, characterized by high number of recurrences and strong resistance to chemo-radio therapy, strongly affecting patients survival. We have recently discovered and studied the small molecule SI113, as inhibitor of SGK1, a serine/threonine protein kinase, that affects several neoplastic phenotypes and signaling cascades. The SI113-dependent SGK1 inhibition induces cell death, blocks proliferation, perturbs cell cycle progression and restores chemo-radio sensibility by modulating SGK1-related substrates. In the present paper we aim to characterize the combined effects of 64CuCl2 and SI113 on human GBM cell lines with variable p53 expression. Methods: Cell viability, cell death and stress/authopagic related pathways were then analyzed by FACS and WB-based assays, after exposure to SI113 and/or 64CuCl2. Results: We demonstrate here, that i) 64CuCl2 is able to induce a time and dose dependent modulation of cell viability (with different IC50 values) in highly malignant gliomas and that the co-treatment with SI113 leads to ii) additive/synergistic effects in terms of cell death; iii) enhancement of the effects of ionizing radiations, probably by a TRC1 modulation; iv) modulation of the autophagic response. Conclusions: Evidence reported here underlines the therapeutic potential of the combined treatment with SI113 and 64CuCl2 in GBM cells.
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- 2017
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12. Temperature Control for an Intra-Mirror Etalon in Interferometric Gravitational Wave Detector Fabry–Perot Cavities
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Jonathan Brooks, Maddalena Mantovani, Annalisa Allocca, Julia Casanueva Diaz, Vincenzo Dattilo, Alain Masserot, and Paolo Ruggi
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etalon ,gravitational waves ,interferometer ,negative feedback control ,classical control ,Astronomy ,QB1-991 - Abstract
The sensitivity of interferometric gravitational wave detectors is optimized, in part, by balanced finesse in the long Fabry–Perot arm cavities. The input test mass mirrors of Advanced Virgo feature parallel faces, which creates an etalon within the substrate, adding variability in the total mirror reflectivity, in order to correct imbalanced finesse due to manufacturing tolerances. Temperature variations in mirror substrate change the optical path length primarily through varying the index of refraction and are tuned to correct for a finesse imbalance of up to 2.8% by a full etalon fringe of 0.257 K. A negative feedback control system was designed to control the mirror temperature by using an electrical resistive heating belt actuator for a heat transfer process modeled as a two-pole plant. A zero controller filter was designed which achieves temperature control within 2.3% of the etalon fringe and recovers to within 10% of the working point within 32 hours after a step input of one etalon fringe. A preliminary unlock condition control designed to compensate when the interferometer unlocks shows that the control remains stable even after a drastic change in the plant due to the absence of the laser heating. Further improvements to the control must also consider the full heat transfer mechanisms by using modern control state space models.
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- 2020
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13. SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition
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Cristina Talarico, Vincenzo Dattilo, Lucia D'Antona, Miranda Menniti, Cataldo Bianco, Francesco Ortuso, Stefano Alcaro, Silvia Schenone, Nicola Perrotti, and Rosario Amato
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SGK1 ,Chemo-resistance ,Radio-resistance ,RAN/RANBP1 ,MDM2 ,SGK1 inhibitors ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
The serum- and glucocorticoid-regulated kinase (SGK) family consists of three members, SGK1, SGK2 and SGK3, all displaying serine/threonine kinase activity and sharing structural and functional similarities with the AKT family of kinases. SGK1 was originally described as a key enzyme in the hormonal regulation of several ion channels and pumps. Over time, growing and impressive evidence has been accumulated, linking SGK1 to the cell survival, de-differentiation, cell cycle control, regulation of caspases, response to chemical, mechanical and oxidative injury in cancer models as well as to the control of mitotic stability. Much evidence shows that SGK1 is over-expressed in a variety of epithelial tumors. More recently, many contributions to the published literature demonstrate that SGK1 can mediate chemo-and radio-resistance during the treatment of various human tumors, both in vitro and in vivo. SGK1 appears therefore as a dirty player in the stress response to chemical and radio-agents, responsible of a selective advantage that favors the uncontrolled tumor progression and the selection of the most aggressive clones. The purpose of this review is the analysis of the literature describing SGK1 as central node of the cell resistance, and a summary of the possible strategies in the pharmacological targeting of SGK1.
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- 2016
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14. Expression of Serum Exosomal miRNA 122 and Lipoprotein Levels in Dogs Naturally Infected by Leishmania infantum: A Preliminary Study
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Antonio Di Loria, Vincenzo Dattilo, Domenico Santoro, Jacopo Guccione, Adriana De Luca, Paolo Ciaramella, Marinella Pirozzi, and Enrico Iaccino
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canine leishmaniasis ,microrna ,mir-122 ,lipoprotein ,exosomes ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Current knowledge on the role of exosomal microRNA (miRNA) in canine leishmaniasis (CL), with particular regards to the interaction between miR-122 and lipid alterations, is limited. The aim of this study was to isolate/characterize exosomes in canine serum and evaluate the expression of miR-122 in ten healthy and ten leishmaniotic dogs. Serum exosomes were isolated using a polymer-based kit, ExoQuick® and characterized by flow cytometry and transmission electron microscopy, whereas miR-122-5p expression was evaluated by quantitative reverse-transcriptase polymerase chain reaction. A significant decreased expression of exosomal miR-122-5p, decreased serum levels of high-density lipoproteins, and increased serum levels of low-density lipoproteins were seen in leishmaniotic dogs when compared with healthy dogs. These results suggest that hepatic dysfunctions induced by the parasite interfere with lipoprotein status. The decreased expression of exosomal miR122 represents an additional effect of Leishmania infection in dogs as in people.
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- 2020
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15. SI113, a Specific Inhibitor of the Sgk1 Kinase Activity that Counteracts Cancer Cell Proliferation
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Lucia D''Antona, Rosario Amato, Cristina Talarico, Francesco Ortuso, Miranda Menniti, Vincenzo Dattilo, Rodolfo Iuliano, Francesco Gigliotti, Anna Artese, Giosuè Costa, Silvia Schenone, Francesca Musumeci, Claudia Abbruzzese, Lorenzo Botta, Francesco Trapasso, Stefano Alcaro, Marco G. Paggi, and Nicola Perrotti
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SGK1 ,Kinase inhibitor ,Cancer ,Necrosis ,Small molecule ,Apoptosis ,Physiology ,QP1-981 ,Biochemistry ,QD415-436 - Abstract
Background/Aims: Published observations on serum and glucocorticoid regulated kinase 1 (Sgk1) knockout murine models and Sgk1-specific RNA silencing in the RKO human colon carcinoma cell line point to this kinase as a central player in colon carcinogenesis and in resistance to taxanes. Methods: By in vitro kinase activity inhibition assays, cell cycle and viability analysis in human cancer model systems, we describe the biologic effects of a recently identified kinase inhibitor, SI113, characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold, that shows specificity for Sgk1. Results: SI113 was able to inhibit in vitro cell growth in cancer cells derived from tumors with different origins. In RKO cells, this kinase inhibitor blocked insulin-dependent phosphorylation of the Sgk1 substrate Mdm2, the main regulator of p53 protein stability, and induced necrosis and apoptosis when used as a single agent. Finally, SI113 potentiated the effects of paclitaxel on cell viability. Conclusion: Since SI113 appears to be effective in inducing cell death in RKO cells, potentiating paclitaxel sensitivity, we believe that this new molecule could be efficiently employed, alone or in combination with paclitaxel, in colon cancer chemotherapy.
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- 2015
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16. Translational aspects of the modern genetics in head and neck cancers
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FRANCESCO PADUANO, EMANUELA ALTOMARE, BENEDETTA MARRELLI, VINCENZO DATTILO, HAIZAL MOHD HUSSAINI, PAUL ROY COOPER, and MARCO TATULLO
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General Medicine - Published
- 2022
17. A novel phage display based platform for exosome diversity characterization
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Domenico Maisano, Selena Mimmi, Vincenzo Dattilo, Fabiola Marino, Massimo Gentile, Eleonora Vecchio, Giuseppe Fiume, Nancy Nisticò, Annamaria Aloisio, Maria Penelope de Santo, Giovanni Desiderio, Vincenzo Musolino, Saverio Nucera, Francesca Sbrana, Sebastiano Andò, Simone Ferrero, Andrea Morandi, Francesco Bertoni, Ileana Quinto, and Enrico Iaccino
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Bacteriophages ,General Materials Science ,Exosomes ,Biomarkers - Abstract
We present an innovative approach allowing the identification, isolation, and molecular characterization of disease-related exosomes based on their different antigenic reactivities. The designed strategy could be immediately translated into any disease in which exosomes are involved. The identification of specific markers and their subsequent association with exosome subtypes, together with the possibility to engineer target-guided exosome-like particles, could represent the key for the effective adoption of exosomes in clinical practice.
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- 2022
18. Genome-wide association studies on Northern Italy isolated populations provide further support concerning genetic susceptibility for major depressive disorder
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Vincenzo Dattilo, Sheila Ulivi, Alessandra Minelli, Martina La Bianca, Edoardo Giacopuzzi, Marco Bortolomasi, Stefano Bignotti, Massimo Gennarelli, Paolo Gasparini, Maria Pina Concas, Dattilo, Vincenzo, Ulivi, Sheila, Minelli, Alessandra, La Bianca, Martina, Giacopuzzi, Edoardo, Bortolomasi, Marco, Bignotti, Stefano, Gennarelli, Massimo, Gasparini, Paolo, and Concas, Maria Pina
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genetic isolates ,Psychiatry and Mental health ,genome-wide association study ,genetic isolate ,Major depressive disorder ,CTNNA2 ,KCNQ5 ,Biological Psychiatry - Abstract
Objectives: Major depressive disorder (MDD) is a psychiatric disorder with pathogenesis influenced by both genetic and environmental factors. To date, the molecular-level understanding of its aetiology remains unclear. Thus, we aimed to identify genetic variants and susceptibility genes for MDD with a genome-wide association study (GWAS) approach. Methods: We performed a meta-analysis of GWASs and a gene-based analysis on two Northern Italy isolated populations (cases/controls n = 166/472 and 33/320), followed by replication and polygenic risk score (PRS) analyses in Italian independent samples (cases n = 464, controls n = 339). Results: We identified two novel MDD-associated genes, KCNQ5 (lead SNP rs867262, p = 3.82 × 10-9) and CTNNA2 (rs6729523, p = 1.25 × 10-8). The gene-based analysis revealed another six genes (p < 2.703 × 10-6): GRM7, CTNT4, SNRK, SRGAP3, TRAPPC9, and FHIT. No replication of the genome-wide significant SNPs was found in the independent cohort, even if 14 SNPs around CTNNA2 showed association with MDD and related phenotypes at the nominal level of p (
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- 2023
19. SARS CoV-2 spike protein-guided exosome isolation facilitates detection of potential miRNA biomarkers in COVID-19 infections
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Selena Mimmi, Anna Maria Zimbo, Salvatore Rotundo, Erika Cione, Nancy Nisticò, Annamaria Aloisio, Domenico Maisano, Anna Maria Tolomeo, Vincenzo Dattilo, Rosaria Lionello, Antonella Fioravanti, Antonio Di Loria, Angela Quirino, Nadia Marascio, Alessandro Russo, Enrico Maria Trecarichi, Giovanni Matera, Ileana Quinto, Carlo Torti, and Enrico Iaccino
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ACE2 ,Covid19 ,biomarkers ,exosomes ,miRNAs ,Biochemistry (medical) ,Clinical Biochemistry ,General Medicine - Abstract
Objectives Nearly three years into the pandemic, SARS-CoV-2 infections are occurring in vaccinated and naturally infected populations. While humoral and cellular responses in COVID-19 are being characterized, novel immune biomarkers also being identified. Recently, an increase in angiotensin-converting enzyme 2 expressing (aka, ACE2 positive) circulating exosomes (ExoACE2) were identified in the plasma of COVID-19 patients (El-Shennawy et al.). In this pilot study, we describe a method to characterize the exosome-associated microRNA (exo-miRNA) signature in ACE2-positive and ACE2-negative exosomal populations (non-ExoACE2). Methods We performed a sorting protocol using the recombinant biotin-conjugated SARS CoV-2 spike protein containing the receptor binding domain (RBD) on plasma samples from six patients. Following purification, exo-miRNA were characterized for ACE2-positive and ACE2-negative exosome subpopulations by RT-PCR. Results We identified differential expression of several miRNA. Specifically let-7g-5p and hsa-miR-4454+miR-7975 were upregulated, while hsa-miR-208a-3p and has-miR-323-3p were downregulated in ExoACE2 vs. non-ExoACE2. Conclusions The SARS CoV-2 spike-protein guided exosome isolation permits isolation of ExoACE2 exosomes. Such purification facilitates detailed characterization of potential biomarkers (e.g. exo-miRNA) for COVID-19 patients. This method could be used for future studies to further the understanding mechanisms of host response against SARS CoV-2.
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- 2023
20. Spotlight on a Short-Time Treatment with the IL-4/IL-13 Receptor Blocker in Patients with CRSwNP: microRNAs Modulations and Preliminary Clinical Evidence
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Selena Mimmi, Nicola Lombardo, Domenico Maisano, Giovanna Piazzetta, Corrado Pelaia, Girolamo Pelaia, Marta Greco, Daniela Foti, Vincenzo Dattilo, and Enrico Iaccino
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miRNAs ,antibody therapeutics ,anti-IL-4/IL-13 receptor ,dupilumab ,nasal polyposis ,interleukins ,T cells ,Genetics ,Genetics (clinical) - Abstract
Already used for the treatment of some allergic and inflammatory diseases, such as asthma or atopic dermatitis, dupilumab has also been approved as add-on therapy for patients with CRSwNP, and it could represent the keystone to reducing the remission time as well as to improve healing and quality of life. On the other hand, the role of miRNAs as potential biomarkers of immune modulation is emerging. We analyzed the effects of a short-time treatment with dupilumab in patients with CRSwNP, analyzing the immune response modification as well as miRNAs modulations. First, in this early observation stage, all patients experienced remarkable improvement and were clinically stable. Indeed, we observed a significant decrease in CD4+ T cells and a significant reduction in total IgE (p < 0.05) and serum IL-8 levels (p < 0.01), indicating a reduction in the general inflammatory condition. In addition, we analyzed a panel of about 200 circulating miRNAs. After treatment, we noted a significant downregulation of hsa-mir-25-3p (p-value = 0.02415) and hsa-mir-185-5p (p-value = 0.04547), two miRNAs involved in the proliferation, inflammation, and dug-resistance, in accordance with the clinical status of patients. All these preliminary data aimed to identify new biomarkers of prognosis, identifiable with non-invasive procedures for patients. Further, these patients are still under observation, and others with different levels of responsiveness to treatment need to be enrolled to increase the statistical data.
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- 2022
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21. LRRK2 kinase inhibition attenuates astrocytic activation in response to amyloid b1-42 fibrils
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Alice Filippini, Valentina Salvi, Vincenzo Dattilo, Chiara Magri, Stefania Castrezzati, Robert Veerhuis, Daniela Bosisio, Massimo Gennarelli, Isabella Russo, Neurochemistry Laboratory, and Amsterdam Neuroscience - Neurodegeneration
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astrocytes ,LRRK2 ,amyloid-β ,Molecular Biology ,Biochemistry ,Alzheimer’s disease ,neuroinflammation ,nervous system diseases - Abstract
Background: Intracerebral accumulation of amyloid-b in the extracellular plaques of Alzheimer’s disease (AD) brains represents the main cause of reactive astrogliosis and neuroinflammatory response. Of relevance, Leucine-Rich-Repeat Kinase 2 (LRRK2), a kinase linked to genetic and sporadic Parkinson’s disease (PD), has been identified as a positive mediator of neuroinflammation upon different inflammatory stimuli, however its pathogenicity in AD remains mainly unexplored. Methods: In this study, by using pharmacological inhibition of LRRK2 and murine primary astrocytes, we explored whether LRRK2 regulates astrocytic activation in response to amyloid-b1-42 (Ab1-42) fibrils. Results: Our results show that primary astrocytes become activated and recruit LRRK2 upon Ab1-42 fibrils exposure. Moreover, we found that pharmacological inhibition of LRRK2, with two different kinase inhibitors, can attenuate Ab1-42-mediated inflammation and favor the clearance of Ab1-42 fibrils in astrocytes. Conclusions: Overall, our findings report that LRRK2 kinase activity modulates astrocytic reactivity and functions in the presence of Ab1-42 deposits and indicate that PD-linked LRRK2 might contribute to AD-related neuroinflammation and pathogenesis.
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- 2022
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22. The seismic isolation system of Advanced Virgo Plus, Phase II
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Andrea Basti, Valerio Boschi, Piero Chessa, Vincenzo Dattilo, Roberto Passaquieti, and Paolo Ruggi
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Nuclear and High Energy Physics ,Instrumentation - Published
- 2023
23. Pathogenic variants in THSD4, encoding the ADAMTS-like 6 protein, predispose to inherited thoracic aortic aneurysm
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Olivier Milleron, Marie Paule Jacob, Benoît Ho-Tin-Noé, Marjolijn Renard, Nadine Hanna, Guillaume Jondeau, Laurent Gouya, Marie Sylvie Gross, Sebastien Dupont, Sandy Elbitar, Sébastien Gaertner, Marianne Abifadel, Jeremie Jonquet, Ketty Kessler, Bertrand Isidor, Catherine Boileau, Yves Alembik, Kiyotoshi Sekiguchi, Dianna M. Milewicz, Laurent Tosolini, Mathilde Varret, Mélodie Aubart, Yara Abou Khalil, Youmna Ghaleb, Dongchuan Guo, Jean-Baptiste Michel, Maud Langeois, Louise Benarroch, Ko Tsutsui, Vincenzo Dattilo, Pauline Arnaud, Julie De Backer, Carine Le Goff, Lynn Y. Sakai, and Petra El Khoury
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0301 basic medicine ,Marfan syndrome ,diagnosis ,Fibrillin-1 ,FIBRONECTIN ,thoracic aortic aneurysm ,THSD4 ,030105 genetics & heredity ,Biology ,Thoracic aortic aneurysm ,DISSECTIONS ,DISEASE ,Article ,Pathogenesis ,Mice ,03 medical and health sciences ,ADAMTSL6 ,medicine.artery ,Medicine and Health Sciences ,medicine ,Animals ,Humans ,Thoracic aorta ,Genetics(clinical) ,Exome ,FBN1 ,Genetics (clinical) ,Exome sequencing ,Genetics ,Aortic Aneurysm, Thoracic ,MUTATIONS ,ADAMTS ,MOUSE MODEL ,FIBRILLIN-1 ,medicine.disease ,GENE ,MARFAN-SYNDROME ,TGFBR2 ,ADAM Proteins ,Aortic Dissection ,030104 developmental biology ,Haploinsufficiency ,Fibrillin - Abstract
Purpose: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD. Methods: We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes in 1114 unrelated TAAD patients. Functional effects of pathogenic variants identified were validated in cell, tissue, and mouse models. Results: We identified five functional variants in THSD4 of which two heterozygous variants lead to a premature termination codon. THSD4 encodes ADAMTSL6 (member of the ADAMTS/L superfamily), a microfibril-associated protein that promotes fibrillin-1 matrix assembly. The THSD4 variants studied lead to haploinsufficiency or impaired assembly of fibrillin-1 microfibrils. Thsd4+/− mice showed progressive dilation of the thoracic aorta. Histologic examination of aortic samples from a patient carrying a THSD4 variant and from Thsd4+/− mice, revealed typical medial degeneration and diffuse disruption of extracellular matrix. Conclusion: These findings highlight the role of ADAMTSL6 in aortic physiology and TAAD pathogenesis. They will improve TAAD management and help develop new targeted therapies.
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- 2021
24. A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions
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Emanuele Bellacchio, Carmela Votino, Vincenzo Dattilo, Cristina Barbara Spoleti, Emma Colao, Sabrina Giglio, Rodolfo Iuliano, Nicola Perrotti, Valentina Bruni, and Andrea La Barbera
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Genetics ,splicing variant ,Achondrogenesis ,in-frame deletion ,minigene assay ,Intron ,COL2A1 ,QH426-470 ,Biology ,skeletal dysplasia ,medicine.disease ,Phenotype ,Exon ,Kniest dysplasia ,Dysplasia ,RNA splicing ,medicine ,achondrogenesis type II ,Genetics (clinical) ,Minigene - Abstract
Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia.
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- 2021
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25. A Novel Splicing Variant of
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Valentina, Bruni, Cristina Barbara, Spoleti, Andrea, La Barbera, Vincenzo, Dattilo, Emma, Colao, Carmela, Votino, Emanuele, Bellacchio, Nicola, Perrotti, Sabrina, Giglio, and Rodolfo, Iuliano
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Adult ,COL2A1 ,splicing variant ,in-frame deletion ,minigene assay ,skeletal dysplasia ,Ultrasonography, Prenatal ,Article ,Achondroplasia ,Alternative Splicing ,Fetal Diseases ,Imaging, Three-Dimensional ,Italy ,Pregnancy ,Mutation ,achondrogenesis type II ,Humans ,Protein Isoforms ,Female ,Collagen Type II ,Abortion, Eugenic ,Sequence Deletion - Abstract
Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia.
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- 2021
26. Predominant VH1-69 IgBCR Clones Show Higher Expression of CD5 in Heterogeneous Chronic Lymphocytic Leukemia Populations
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Mariangela Scalise, Ileana Quinto, Vincenzo Dattilo, Eleonora Vecchio, Annamaria Aloisio, Federico Chiurazzi, Massimo Gentile, Selena Mimmi, Giuseppe Fiume, Erika De Sensi, Enrico Iaccino, Domenico Augusto Francesco Maisano, Alessandro D’Ambrosio, and Nancy Nisticò
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0301 basic medicine ,Cancer Research ,Phage display ,Chronic lymphocytic leukemia ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,peptide-based sorting ,immune system diseases ,hemic and lymphatic diseases ,Gene expression ,medicine ,Neoplastic transformation ,RC254-282 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Brief Research Report ,medicine.disease ,Phenotype ,immunoglobulin B cell receptor ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,gene expression ,Cancer research ,chronic lymphocytic leukemia ,phage display ,CD5 ,Carcinogenesis - Abstract
The immunoglobulin B cell receptor (IgBCR) expressed by chronic lymphocytic leukemia (CLL) B cells plays a pivotal role in tumorigenesis, supporting neoplastic transformation, survival, and expansion of tumor clones. We demonstrated that in the same patient, two or more CLL clones could coexist, recognized by the expression of different variable regions of the heavy chain of IgBCR, composing the antigen-binding site. In this regard, phage display screening could be considered the easier and most advantageous methodology for the identification of small peptide molecules able to mimic the natural antigen of the tumor IgBCRs. These molecules, properly functionalized, could be used as a probe to specifically identify and isolate single CLL subpopulations, for a deeper analysis in terms of drug resistance, phenotype, and gene expression. Furthermore, CLL cells express another surface membrane receptor, the CD5, which is commonly expressed by normal T cells. Piece of evidence supports a possible contribution of CD5 to the selection and maintenance of autoreactivity in B cells and the constitutive expression of CD5 on CLL cells could induce pro-survival stimuli. In this brief research report, we describe a peptide-based single-cell sorting using as bait the IgBCR of tumor cells; in the next step, we performed a quantitative analysis of CD5 expression by qRT-PCR related to the expressed IgBCR. Our approach could open a new perspective for the identification, isolation, and investigation of all subsets of IgBCR-related CLL clones, with particular attention to the more aggressive clones.
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- 2021
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27. In Preclinical Model of Ovarian Cancer, the SGK1 Inhibitor SI113 Counteracts the Development of Paclitaxel Resistance and Restores Drug Sensitivity
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Vincenzo Dattilo, Cristina Barbara Spoleti, Giuseppe Perrotti, Nicola Costa, Nicola Perrotti, Claudia Vincenza Fiumara, Rodolfo Iuliano, Rosario Amato, Francesca Musumeci, Domenica Scumaci, Lucia D'Antona, Silvia Schenone, Giovanni Cuda, Giada Catalogna, and Rossana Tallerico
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0301 basic medicine ,Original article ,Cancer Research ,medicine.medical_treatment ,lcsh:RC254-282 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ovarian carcinoma ,medicine ,Nuclear protein ,Chemotherapy ,business.industry ,Kinase ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Radiation therapy ,030104 developmental biology ,Oncology ,Paclitaxel ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Ovarian cancer ,business - Abstract
Ovarian cancer is the second most common gynecological malignancy worldwide. Paclitaxel is particularly important in the therapy of ovarian carcinomas, but the treatment efficacy is counteracted by the development of resistance to chemotherapy. The identification of target molecules that can prevent or control the development of chemoresistance might provide important tools for the management of patients affected by ovarian cancer. Serum- and glucocorticoid-regulated kinase 1 (SGK1) appears to be a key determinant of resistance to chemo- and radiotherapy. Specifically, SGK1 affects paclitaxel sensitivity in RKO colon carcinoma cells by modulating the specificity protein 1 (SP1)–dependent expression of Ran-specific GTPase-activating protein (RANBP1), a member of the GTP-binding nuclear protein Ran (RAN) network that is required for the organization and function of the mitotic spindle. SGK1 inhibition might thus be useful for counteracting the development of paclitaxel resistance. Here, we present in vitro data obtained using ovarian carcinoma cell lines that indicate that the SGK1 inhibitor SI113 inhibits cancer cell proliferation, potentiates the effects of paclitaxel-based chemotherapy, counteracts the development of paclitaxel resistance, and restores paclitaxel sensitivity in paclitaxel-resistant A2780 ovarian cancer cells. The results were corroborated by preclinical studies of xenografts generated in nude mice through the implantation of paclitaxel-resistant human ovarian cancer cells. The SGK1 inhibitor SI113 synergizes with paclitaxel in the treatment of xenografted ovarian cancer cells. Taken together, these data suggest that SGK1 inhibition should be investigated in clinical trials for the treatment of paclitaxel-resistant ovarian cancer.
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- 2019
28. Temperature Control for an Intra-Mirror Etalon in Interferometric Gravitational Wave Detector Fabry–Perot Cavities
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P. Ruggi, A. Masserot, Julia Casanueva Diaz, M. Mantovani, A. Allocca, J. Brooks, Vincenzo Dattilo, Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Brooks, J., Mantovani, M., Allocca, A., Diaz, J. C., Dattilo, V., Masserot, A., and Ruggi, P.
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neutron star: binary ,Physics::Instrumentation and Detectors ,Physics::Optics ,cavity: optical ,01 natural sciences ,lcsh:QB1-991 ,Finesse ,detector: calibration ,Interferometric gravitational wave detector ,Physics ,Detector ,Astrophysics::Instrumentation and Methods for Astrophysics ,detector: upgrade ,Interferometry ,experimental equipment ,gravitational waves ,interferometer: sensitivity ,Gravitational wave ,detector: performance ,etalon ,lcsh:Astronomy ,interferometer ,mirror: absorption ,negative feedback control ,010309 optics ,General Relativity and Quantum Cosmology ,Optics ,binary: coalescence ,Control theory ,0103 physical sciences ,[PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det] ,010306 general physics ,Optical path length ,control system: feedback ,Temperature control ,business.industry ,gravitational radiation ,Astronomy and Astrophysics ,stability ,laser ,detector: sensitivity ,VIRGO ,path length: optical ,gravitational radiation detector: interferometer ,High Energy Physics::Experiment ,classical control ,galaxy ,business ,Fabry–Pérot interferometer ,experimental results - Abstract
The sensitivity of interferometric gravitational wave detectors is optimized, in part, by balanced finesse in the long Fabry&ndash, Perot arm cavities. The input test mass mirrors of Advanced Virgo feature parallel faces, which creates an etalon within the substrate, adding variability in the total mirror reflectivity, in order to correct imbalanced finesse due to manufacturing tolerances. Temperature variations in mirror substrate change the optical path length primarily through varying the index of refraction and are tuned to correct for a finesse imbalance of up to 2.8% by a full etalon fringe of 0.257 K. A negative feedback control system was designed to control the mirror temperature by using an electrical resistive heating belt actuator for a heat transfer process modeled as a two-pole plant. A zero controller filter was designed which achieves temperature control within 2.3% of the etalon fringe and recovers to within 10% of the working point within 32 hours after a step input of one etalon fringe. A preliminary unlock condition control designed to compensate when the interferometer unlocks shows that the control remains stable even after a drastic change in the plant due to the absence of the laser heating. Further improvements to the control must also consider the full heat transfer mechanisms by using modern control state space models.
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- 2020
29. Expression of Serum Exosomal miRNA 122 and Lipoprotein Levels in Dogs Naturally Infected by Leishmania infantum: A Preliminary Study
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Jacopo Guccione, Enrico Iaccino, Domenico Santoro, Adriana De Luca, Vincenzo Dattilo, Marinella Pirozzi, Paolo Ciaramella, Antonio Di Loria, DI LORIA, Antonio, Dattilo, Vincenzo, Santoro, Domenico, Guccione, Jacopo, DE LUCA, Adriana, Ciaramella, Paolo, Pirozzi, Marinella, and Iaccino, Enrico
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microrna ,exosomes ,Article ,Flow cytometry ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,lcsh:Zoology ,Canine leishmaniasis ,medicine ,MiR-122 ,canine leishmaniasis ,lcsh:QL1-991 ,Polymerase chain reaction ,030304 developmental biology ,0303 health sciences ,lcsh:Veterinary medicine ,General Veterinary ,biology ,medicine.diagnostic_test ,lipoprotein ,medicine.disease ,Leishmania ,biology.organism_classification ,Microvesicles ,3. Good health ,mir-122 ,030220 oncology & carcinogenesis ,Immunology ,lcsh:SF600-1100 ,Animal Science and Zoology ,Leishmania infantum ,canine leishmaniasi ,Lipoprotein - Abstract
Current knowledge on the role of exosomal microRNA (miRNA) in canine leishmaniasis (CL), with particular regards to the interaction between miR-122 and lipid alterations, is limited. The aim of this study was to isolate/characterize exosomes in canine serum and evaluate the expression of miR-122 in ten healthy and ten leishmaniotic dogs. Serum exosomes were isolated using a polymer-based kit, ExoQuick®, and characterized by flow cytometry and transmission electron microscopy, whereas miR-122-5p expression was evaluated by quantitative reverse-transcriptase polymerase chain reaction. A significant decreased expression of exosomal miR-122-5p, decreased serum levels of high-density lipoproteins, and increased serum levels of low-density lipoproteins were seen in leishmaniotic dogs when compared with healthy dogs. These results suggest that hepatic dysfunctions induced by the parasite interfere with lipoprotein status. The decreased expression of exosomal miR122 represents an additional effect of Leishmania infection in dogs as in people.
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- 2020
30. Identification of differentially expressed microRNAs in the skin of experimentally sensitized naturally affected atopic beagles by next-generation sequencing
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Enrico Iaccino, Antonio Di Loria, Donatella Malanga, Rosanna Marsella, Domenico Santoro, Teresa Mirante, Duarte Mendes Oliveira, Paolo Ciaramella, Carmelo Laudanna, Vincenzo Dattilo, Santoro, Domenico, DI LORIA, Antonio, Mirante, Teresa, Mendes Oliveira, Duarte, Laudanna, Carmelo, Malanga, Donatella, Dattilo, Vincenzo, Iaccino, Enrico, Marsella &, Rosanna, and Ciaramella, Paolo
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0301 basic medicine ,Small RNA ,Allergy ,Immunology ,Gene Expression ,Genome-wide association study ,Biology ,Beagle ,Dermatitis, Atopic ,03 medical and health sciences ,Dogs ,0302 clinical medicine ,microRNA ,Genetics ,medicine ,Animals ,Dog Diseases ,Skin ,Dermatophagoides farinae ,integumentary system ,High-Throughput Nucleotide Sequencing ,Reproducibility of Results ,Atopic dermatitis ,medicine.disease ,Human genetics ,MicroRNAs ,030104 developmental biology ,Case-Control Studies ,microRNA, dog, Atopic dermatitis, skin ,DNA microarray ,030215 immunology - Abstract
Canine atopic dermatitis (AD) is a very common inflammatory skin disease, but limited data are available on the genetic characterization (somatic mutations, microarrays, and genome-wide association study (GWAS)) of skin lesions in affected dogs. microRNAs are good biomarkers in inflammatory and neoplastic diseases in people. The aim of this study was to evaluate microRNA expression in the skin of atopic beagles, before and after exposure to Dermatophagoides farinae. Four atopic and four unrelated age-matched healthy beagle dogs were enrolled. Total RNA was extracted from flash-frozen skin biopsies of healthy and atopic dogs. For the atopic dogs, skin biopsies were taken from non-lesional (day 0) and lesional skin (day 28 of weekly environmental challenge with Dermatophagoides farinae). Small RNA libraries were constructed and sequenced. The microRNA sequences were aligned to CanFam3.1 genome. Differential expressed microRNAs were selected on the basis of fold-change and statistical significance (fold-change ≥ 1.5 and p ≤ 0.05 as thresholds. A total of 277 microRNAs were sequenced. One hundred and twenty-one differentially regulated microRNAs were identified between non-lesional and healthy skin. Among these, two were increased amount and 119 were decreased amount. A total of 45 differentially regulated microRNAs between lesional and healthy skin were identified, 44 were decreased amount and one was increased amount. Finally, only two increased amount microRNAs were present in lesional skin when compared with that of non-lesional skin. This is the first study in which dysregulation of microRNAs has been associated with lesional and non-lesional canine AD. Larger studies are needed to understand the role of microRNA in canine AD.
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- 2020
31. Deregulation of SGK1 in Ulcerative Colitis: A Paradoxical Relationship Between Immune Cells and Colonic Epithelial Cells
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Vincenzo Dattilo, Rodolfo Iuliano, V. Cosco, Rosellina Margherita Mancina, Caterina Camastra, Francesco Conforti, Patrizia Doldo, Giada Catalogna, Valeria Ventura, Ennio Carbone, Rosario Amato, C. Cosco, Nicola Perrotti, Rossana Tallerico, Lucia D'Antona, and Rocco Spagnuolo
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,Colon ,medicine.medical_treatment ,Down-Regulation ,Inflammation ,Protein Serine-Threonine Kinases ,Inflammatory bowel disease ,Jurkat cells ,Cell Line ,Immediate-Early Proteins ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Immunology and Allergy ,RNA, Messenger ,Intestinal Mucosa ,Interleukin-13 ,urogenital system ,business.industry ,Interleukin-17 ,Gastroenterology ,Epithelial Cells ,medicine.disease ,030104 developmental biology ,Cytokine ,030220 oncology & carcinogenesis ,Interleukin 13 ,Leukocytes, Mononuclear ,Cancer research ,Th17 Cells ,Colitis, Ulcerative ,Interleukin 17 ,medicine.symptom ,business - Abstract
BACKGROUND Inflammatory bowel disease (IBD) is due to the interaction of genetic and environmental factors that trigger an unbalanced immune response ultimately resulting in the peculiar inflammatory reaction. Experimental models of IBD point to a role of T-cell-derived cytokines (Th17) and to SGK1 as mediator of the Th17 switch. We hypothesize that SGK1, a salt inducible kinase, directs lymphocytic behavior and tissue damage. METHODS Eleven controls and 32 ulcerative colitis (UC) patients were randomized according to endoscopic Mayo score. Mucosal biopsies from different intestinal tracts were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction to check the expression of disease markers including SGK1. Peripheral blood mononuclear cells (PBMCs) from patients and controls were analyzed by fluorescence-activated cell sorting. Finally, an in vitro cell model was developed to test the hypothesis. RESULTS SGK1 mRNA and protein expression in lesional areas of UC patients were lower than in normal peri-lesional areas of the same patients and in normal tissues of healthy controls. SGK1 expression was increased in PBMCs from UC patients, particularly in the CD4+ cell population, enriched in Th17 cells. IL17/IL13 was increased in patients and correlated with SGK1 expression. Genetically engineered Jurkat cells confirmed the effect of SGK1 overexpression on viability of RKO cells. CONCLUSIONS These observations suggest a pathogenic mechanism whereby SGK1 overexpression in CD4+ T cells induces the secretion of the inflammatory cytokines IL17 and IL13, which downregulate the expression of SGK1 in target tissues. Our data suggest a novel hypothesis in the pathogenesis of UC, integrating colonic epithelial cells and lymphocytes.
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- 2018
32. A novel ABCC6 variant causative of pseudoxanthoma elasticum
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Fernanda Fabiani, Uros Hladnik, Vincenzo Dattilo, Gianluca Contrò, Steven Paul Nisticò, Rossana Tallerico, Rodolfo Iuliano, Maria Vittoria Enzo, Emma Colao, Nicola Perrotti, and Stefano Dastoli
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medicine.medical_specialty ,lcsh:QH426-470 ,lcsh:Life ,ABCC6 ,Diseases ,Biology ,Biochemistry ,Genetic analysis ,03 medical and health sciences ,Exon ,Genetics ,medicine ,Data Report ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Messenger RNA ,030305 genetics & heredity ,Medical genetics ,Pseudoxanthoma elasticum ,medicine.disease ,lcsh:Genetics ,lcsh:QH501-531 ,Clinical diagnosis ,RNA splicing ,biology.protein - Abstract
Pseudoxanthoma elasticum is an autosomal recessive heritable disorder caused by mutations in ABCC6. We describe two siblings showing typical skin lesions and a clinical diagnosis of pseudoxanthoma elasticum. Genetic analysis of ABCC6 revealed a novel homozygous c.4041G > A variant located in the last position of exon 28 that compromises the splicing donor site, resulting in a shorter messenger RNA. The deletion impairs the nucleotide-binding fold region, which is crucial for ABCC6 function.
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- 2019
33. SI113, a SGK1 inhibitor, potentiates the effects of radiotherapy, modulates the response to oxidative stress and induces cytotoxic autophagy in human glioblastoma multiforme cells
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Cristina Talarico, Tullio Florio, Francesco Trapasso, Rosario Amato, Francesca Musumeci, Francesco Ortuso, Vincenzo Dattilo, Cataldo Bianco, Lucia D'Antona, Stefano Alcaro, Nicola Amodio, Agnese Barone, Marco G. Paggi, Nicola Perrotti, Silvia Schenone, Claudia Abbruzzese, and Stefania Belviso
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0301 basic medicine ,Programmed cell death ,Radiation-Sensitizing Agents ,Cell Survival ,Antineoplastic Agents ,Protein Serine-Threonine Kinases ,medicine.disease_cause ,Immediate-Early Proteins ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Autophagy ,Medicine ,Cytotoxic T cell ,Humans ,Viability assay ,SGK1 ,Protein kinase A ,radiotherapy ,Cell Proliferation ,business.industry ,Cell growth ,glioblastoma ,Chemoradiotherapy ,Oxidative Stress ,030104 developmental biology ,Pyrimidines ,Oncology ,030220 oncology & carcinogenesis ,SI113 ,Immunology ,Cancer research ,SGK1, SI113, radiotherapy, glioblastoma, oxidative stress ,Pyrazoles ,business ,Oxidative stress ,Research Paper - Abstract
Glioblastoma multiforme (GBM) is the most aggressive CNS tumor and is characterized by a very high frequency of clinical relapse after therapy and thus by a dismal prognosis, which strongly compromises patients survival. We have recently identified the small molecule SI113, as a potent and selective inhibitor of SGK1, a serine/threonine protein kinase, that modulates several oncogenic signaling cascades. The SI113-dependent SGK1 inhibition induces cell death, blocks proliferation and perturbs cell cycle progression by modulating SGK1-related substrates. SI113 is also able to strongly and consistently block, in vitro and in vivo, growth and survival of human hepatocellular-carcinomas, either used as a single agent or in combination with ionizing radiations. In the present paper we aim to study the effect of SI113 on human GBM cell lines with variable p53 expression. Cell viability, cell death, caspase activation and cell cycle progression were then analyzed by FACS and WB-based assays, after exposure to SI113, with or without oxidative stress and ionizing radiations. Moreover, autophagy and related reticulum stress response were evaluated. We show here, that i) SGK1 is over-expressed in highly malignant gliomas and that the treatment with SI113 leads to ii) significant increase in caspase-mediated apoptotic cell death in GBM cell lines but not in normal fibroblasts; iii)enhancement of the effects of ionizing radiations; iv) modulation of the response to oxidative reticulum stress; v) induction of cytotoxic autophagy. Evidence reported here underlines the therapeutic potential of SI113 in GBM, suggesting a new therapeutic strategy either alone or in combination with radiotherapy.
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- 2016
34. Review about the multi-target profile of resveratrol and its implication in the SGK1 inhibition
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Rodolfo Iuliano, Francesco Ortuso, Rosario Amato, Nicola Perrotti, Lucia D'Antona, Giada Catalogna, Vincenzo Dattilo, Federica Moraca, Giuseppe Perrotti, Antonio Lupia, Francesco Trapasso, Giosuè Costa, and Stefano Alcaro
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Cardiotonic Agents ,Cell Survival ,Anti-Inflammatory Agents ,Antineoplastic Agents ,Protein Serine-Threonine Kinases ,Resveratrol ,Pharmacology ,01 natural sciences ,Neuroprotection ,Antioxidants ,Immediate-Early Proteins ,03 medical and health sciences ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Molecular Targeted Therapy ,030304 developmental biology ,0303 health sciences ,Natural product ,010405 organic chemistry ,Cell growth ,Organic Chemistry ,food and beverages ,General Medicine ,0104 chemical sciences ,Neuroprotective Agents ,Mechanism of action ,chemistry ,Docking (molecular) ,Cancer cell ,medicine.symptom ,Signal transduction - Abstract
Resveratrol (trans-3,4’,5-trihydroxystilbene) is a polyphenolic natural product with a well-known polypharmacological profile that places it among the multi-target-directed ligands (MTDLs). Given its protective action against a wide number of chronic diseases, in this review, we introduce a general overview about the cardioprotective and antioxidant effects, the antidiabetic, neuroprotective and anti-inflammatory effects of this polyphenol. In the second part of the manuscript, we focused our attention on the anticancer activity of Resveratrol, given the alteration of many different signaling pathways, leading to suppression of tumor cell proliferation in numerous cancer types. Among the several anticancer targets involved in the mechanism of action of Resveratrol, here we introduce experimental and molecular modeling studies performed against the SGK1 protein as a novel anticancer target of Resveratrol. SGK1 inhibitors have been demonstrated to inhibit cell growth of different cancer cells. We demonstrated that resveratrol inhibits SGK1 in vitro and in intact cells, affecting proliferation and survival of HUH7 human hepatoma cells. Our findings demonstrate that resveratrol may function as a SGK1 inhibitor, suggesting possible applications in sodium retention and cancer.
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- 2019
35. Abstract B122: The CD98hc oncoprotein as a target of new anticancer therapy
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Patrizia Cantafio, Delia Lanzillotta, Anna Artese, Eugenio Gaudio, Giosuè Costa, Stefano Alcaro, Vincenzo Dattilo, Isabella Romeo, Carolina Brescia, Francesco Trapasso, Selena Mimmi, Enrico Iaccino, and Sabrina D'Agostino
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Cancer Research ,Phage display ,Cell growth ,Chemistry ,In silico ,Cancer ,Protein tyrosine phosphatase ,medicine.disease ,Transmembrane protein ,Oncology ,Cancer research ,medicine ,Protein kinase B ,PI3K/AKT/mTOR pathway - Abstract
Among the proteins putatively interacting with PTPRJ, a tyrosine phosphatase with tumor suppressor activity, we focused on the oncoprotein CD98hc as a very interesting candidate for the development of innovative targeted drugs. In fact, CD98hc, representing the heavy chain of a transmembrane aminoacid transporter, is overexpressed in several human cancers. Furthermore, CD98hc higher expression is associated with poor prognosis in lung cancer patients. CD98hc is linked to light chains (LATs, xCT) by disulfide bridge, polar and hydrophobic interactions. The light chain confers substrate specificity, and ERK, AKT, FAK and mTOR pathways are involved in CD98hc-LATs/xCT downstream signals. Moreover, CD98hc is a coreceptor of b-integrins and it is involved in cell proliferation, migration and invasion. We identified two peptides and 15 small molecules (putatively targeting the disulfide bridge) as candidate CD98hc inhibitors by phage display and in silico screenings, respectively, and validated in vitro the binding between peptides and transmembrane fraction of CD98hc by cytofluorimetric assay. Then, we tested the capability of both types of compounds to affect cell viability and proliferation through MTT and CFSE assays, respectively. We observed that the targeting of CD98hc through both peptides and small molecules reduced cell proliferation in A549 human lung cancer cells, strongly encouraging a deeper characterization of these candidate anticancer molecules. Indeed, our next goals will be the assessment of biochemical activity of CD98hc following to its inhibition, as well as the evaluation of compounds toxicity, both in vitro and in vivo. The final aim is to identify lead compounds inhibiting CD98hc, in order to develop novel molecules to be translated in the clinical setting and to be used as monotherapy and/or in a combinatorial approaches for the treatment of cancer patients. Citation Format: Delia Lanzillotta, Enrico Iaccino, Anna Artese, Selena Mimmi, Sabrina D'Agostino, Isabella Romeo, Patrizia Cantafio, Vincenzo Dattilo, Giosuè Costa, Carolina Brescia, Eugenio Gaudio, Stefano Alcaro, Francesco Trapasso. The CD98hc oncoprotein as a target of new anticancer therapy [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B122. doi:10.1158/1535-7163.TARG-19-B122
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- 2019
36. The receptor protein tyrosine phosphatase PTPRJ negatively modulates the CD98hc oncoprotein in lung cancer cells
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Camillo Palmieri, Cirino Botta, Vincenzo Dattilo, Delia Lanzillotta, Rosario Amato, Eugenio Gaudio, Stefania Scalise, Nicola Perrotti, Alfredo Fusco, Cesare Indiveri, Antonio Baldrini, Anna Bilotta, Marco Gaspari, Mariaconcetta Varano, Rodolfo Iuliano, Sabrina D'Agostino, Francesco Paduano, Francesco Trapasso, D'Agostino, S, Lanzillotta, D, Varano, M, Botta, C, Baldrini, A, Bilotta, A, Scalise, S, Dattilo, V, Amato, R, Gaudio, E, Paduano, F, Palmieri, C, Iuliano, R, Perrotti, N, Indiveri, C, Fusco, A, Gaspari, M, Trapasso, F., D'Agostino S., Lanzillotta D., Varano M., Botta C., Baldrini A., Bilotta A., Scalise S., Dattilo V., Amato R., Gaudio E., Paduano F., Palmieri C., Iuliano R., Perrotti N., Indiveri C., Fusco A., Gaspari M., and Trapasso F.
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0301 basic medicine ,CD98hc ,Chemistry ,Cell growth ,Cell ,PTPRJ ,Protein tyrosine phosphatase ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,medicine.anatomical_structure ,Proteasomal degradation ,Oncology ,MG132 ,Cancer cell ,Cancer research ,medicine ,Proteasome inhibitor ,Gene silencing ,Lung cancer ,Carcinogenesis ,medicine.drug ,Research Paper - Abstract
PTPRJ, a receptor protein tyrosine phosphatase strongly downregulated in human cancer, displays tumor suppressor activity by negatively modulating several proteins involved in proliferating signals. Here, through a proteomic-based approach, we identified a list of potential PTPRJ-interacting proteins and among them we focused on CD98hc, a type II glycosylated integral membrane protein encoded by SLC3A2, corresponding to the heavy chain of a heterodimeric transmembrane amino-acid transporter, including LAT1. CD98hc is widely overexpressed in several types of cancers and contributes to the process of tumorigenesis by interfering with cell proliferation, adhesion, and migration. We first validated PTPRJ-CD98hc interaction, then demonstrated that PTPRJ overexpression dramatically reduces CD98hc protein levels in A549 lung cancer cells. In addition, following to the treatment of PTPRJ-transduced cells with MG132, a proteasome inhibitor, CD98hc levels did not decrease compared to controls, indicating that PTPRJ is involved in the regulation of CD98hc proteasomal degradation. Moreover, PTPRJ overexpression combined with CD98hc silencing consistently reduced cell proliferation and triggered apoptosis of lung cancer cells. Interestingly, by interrogating the can Evolve database, we observed an inverse correlation between PTPRJ and SLC3A2 gene expression. Indeed, the non-small cell lung cancers (NSCLCs) of patients showing a short survival rate express the lowest and the highest levels of PTPRJ and SLC3A2, respectively. Therefore, the results reported here contribute to shed lights on PTPRJ signaling in cancer cells: moreover, our findings also support the development of a novel anticancer therapeutic approach by targeting the pathway of PTPRJ that is usually downregulated in highly malignant human neoplasias.
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- 2018
37. The small molecule SI113 synergizes with mitotic spindle poisons in arresting the growth of human glioblastoma multiforme
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Claudia Abbruzzese, Nicola Perrotti, Mariantonia Carosi, Marco G. Paggi, Rosario Amato, Francesca Musumeci, Patrizia Lavia, Giada Catalogna, Vincenzo Dattilo, Simona di Martino, Anna Maria Mileo, Silvia Schenone, and Enzo Gallo
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0301 basic medicine ,[object Object] ,vincristine ,03 medical and health sciences ,chemistry.chemical_compound ,glioblastoma multiforme ,0302 clinical medicine ,In vivo ,medicine ,Cytotoxic T cell ,SGK1 ,Clonogenic assay ,in vivo cancer therapy ,business.industry ,urogenital system ,Glioblastoma multiforme ,In vivo cancer therapy ,SI113 ,Vincristine ,Oncology ,Virology ,Spindle apparatus ,Spindle poison ,030104 developmental biology ,Paclitaxel ,chemistry ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,business ,medicine.drug ,Research Paper - Abstract
Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM therapy often fails to ensure control of a disease characterized by high frequency of recurrences and progression. In search for novel therapeutic approaches, we assayed the effect of compounds from a cancer drug library on the ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle poisons. Our previous work showed that the effectiveness of the spindle poison paclitaxel in inhibiting cancer cell growth was dependent on the expression of RANBP1, a regulatory target of the serine/threonine kinase SGK1. Recently, we developed the small molecule SI113 to inhibit SGK1 activity. Therefore, we explored the outcome of the association between SI113 and selected spindle poisons, finding that these drugs generated a synergistic cytotoxic effect in GBM cells, drastically reducing their viability and clonogenic capabilities in vitro, as well as inhibiting tumor growth in vivo. We also defined the molecular bases of such a synergistic effect. Because SI113 displays low systemic toxicity, yet strong activity in potentiating the effect of radiotherapy in GBM cells, we believe that this drug could be a strong candidate for clinical trials, with the aim to add it to the current GBM therapeutic approaches.
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- 2017
38. The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells
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Vincenzo Dattilo, Rosario Amato, Lucia D'Antona, Francesca Musumeci, Silvia Schenone, Giuseppe Lucio Cascini, Nicola Perrotti, Vincenzo Gangemi, Cataldo Bianco, Cristina Talarico, Ferdinando Calabria, and Giada Catalogna
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0301 basic medicine ,Cyclin-Dependent Kinase Inhibitor p21 ,Programmed cell death ,Ionizing ,Physiology ,Cell Survival ,64CuCl2 ,GBM ,SGK1 ,SI113 ,Apoptosis ,Brain Neoplasms ,Cell Line, Tumor ,Copper ,Drug Synergism ,Glioblastoma ,Humans ,Immediate-Early Proteins ,Protein Kinase Inhibitors ,Protein-Serine-Threonine Kinases ,Pyrazoles ,Pyrimidines ,Radiation, Ionizing ,Signal Transduction ,Tumor Suppressor Protein p53 ,Protein Serine-Threonine Kinases ,lcsh:Physiology ,Cell Line ,lcsh:Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,medicine ,lcsh:QD415-436 ,Viability assay ,Protein kinase A ,Tumor ,Radiation ,lcsh:QP1-981 ,Kinase ,Chemistry ,Cancer ,medicine.disease ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Radionuclide therapy ,Cancer research - Abstract
Background/Aims: The importance of copper in the metabolism of cancer cells has been widely studied in the last 20 years and a clear-cut association between copper levels and cancer deregulation has been established. Copper-64, emitting positrons and β-radiations, is indicated for the labeling of a large number of molecules suitable for radionuclide imaging as well as radionuclide therapy. Glioblastoma multiforme (GBM) is the CNS tumor with the worse prognosis, characterized by high number of recurrences and strong resistance to chemo-radio therapy, strongly affecting patients survival. We have recently discovered and studied the small molecule SI113, as inhibitor of SGK1, a serine/threonine protein kinase, that affects several neoplastic phenotypes and signaling cascades. The SI113-dependent SGK1 inhibition induces cell death, blocks proliferation, perturbs cell cycle progression and restores chemo-radio sensibility by modulating SGK1-related substrates. In the present paper we aim to characterize the combined effects of 64CuCl2 and SI113 on human GBM cell lines with variable p53 expression. Methods: Cell viability, cell death and stress/authopagic related pathways were then analyzed by FACS and WB-based assays, after exposure to SI113 and/or 64CuCl2. Results: We demonstrate here, that i) 64CuCl2 is able to induce a time and dose dependent modulation of cell viability (with different IC50 values) in highly malignant gliomas and that the co-treatment with SI113 leads to ii) additive/synergistic effects in terms of cell death; iii) enhancement of the effects of ionizing radiations, probably by a TRC1 modulation; iv) modulation of the autophagic response. Conclusions: Evidence reported here underlines the therapeutic potential of the combined treatment with SI113 and 64CuCl2 in GBM cells.
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- 2017
39. A novel splice variant of the protein tyrosine phosphatase PTPRJ that encodes for a soluble protein involved in angiogenesis
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Nicola Perrotti, Francesco Trapasso, Stefania Belviso, Alfredo Fusco, Eugenio Gaudio, Sabrina D'Agostino, Rodolfo Iuliano, Francesco Paduano, Anna Bilotta, Tullio Florio, Stefania Scalise, Mariaconcetta Bilotta, Vincenzo Dattilo, Bilotta, Anna, Dattilo, Vincenzo, D'Agostino, Sabrina, Belviso, Stefania, Scalise, Stefania, Bilotta, Mariaconcetta, Gaudio, Eugenio, Paduano, Francesco, Perrotti, Nicola, Florio, Tullio, Fusco, Alfredo, Iuliano, Rodolfo, and Trapasso, Francesco
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0301 basic medicine ,Time Factors ,Glycosylation ,Angiogenesis ,Protein tyrosine phosphatase ,HeLa Cell ,0302 clinical medicine ,MCF-7 Cell ,HEK293 Cell ,Cell Movement ,Neoplasms ,Medicine ,Protein Isoforms ,Receptor ,Tube formation ,Neovascularization, Pathologic ,Cell adhesion molecule ,Receptor-Like Protein Tyrosine Phosphatases, Class 3 ,Gene Expression Regulation, Neoplastic ,Angiogenesi ,Ectodomain ,Oncology ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Research Paper ,Human ,Signal Transduction ,Gene isoform ,Time Factor ,Immunoprecipitation ,Human Umbilical Vein Endothelial Cell ,Neovascularization, Physiologic ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,Human Umbilical Vein Endothelial Cells ,Cell Adhesion ,Humans ,RNA, Messenger ,A549 Cell ,Cell Proliferation ,business.industry ,Protein Isoform ,Soluble isoform ,Molecular biology ,Angiogenic factor ,Glioblastoma ,030104 developmental biology ,HEK293 Cells ,Solubility ,A549 Cells ,Cell Adhesion Molecule ,Immunology ,Neoplasm ,Neoplasm Grading ,business ,Cell Adhesion Molecules ,HeLa Cells - Abstract
// Anna Bilotta 1 , Vincenzo Dattilo 2 , Sabrina D'Agostino 1 , Stefania Belviso 1 , Stefania Scalise 1 , Mariaconcetta Bilotta 1 , Eugenio Gaudio 1, 3 , Francesco Paduano 1, 4 , Nicola Perrotti 2 , Tullio Florio 5 , Alfredo Fusco 6 , Rodolfo Iuliano 1 , Francesco Trapasso 1 1 Department of Medicina Sperimentale e Clinica, University Magna Graecia of Catanzaro, Catanzaro, Italy 2 Department of Scienze della Salute, University Magna Graecia of Catanzaro, Catanzaro, Italy 3 Lymphoma and Genomics Research Program, Institute of Oncology Research (IOR), Bellinzona, Switzerland 4 Tecnologica Research Institute, Biomedical Section, Crotone, Italy 5 Laboratory of Pharmacology, Dept. of Internal Medicine, and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genova, Italy 6 Istituto di Endocrinologia e Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, University Federico II of Napoli, Napoli, Italy Correspondence to: Rodolfo Iuliano, email: iuliano@unicz.it Francesco Trapasso, email: trapasso@unicz.it Keywords: protein tyrosine phosphatase, soluble isoform, angiogenesis, glioblastoma, angiogenic factor Received: September 20, 2016 Accepted: December 13, 2016 Published: December 29, 2016 ABSTRACT PTPRJ is a receptor protein tyrosine phosphatase with tumor suppressor activity. Very little is known about the role of PTPRJ ectodomain, although recently both physiological and synthetic PTPRJ ligands have been identified. A putative shorter spliced variant, coding for a 539 aa protein corresponding to the extracellular N-terminus of PTPRJ, is reported in several databases but, currently, no further information is available. Here, we confirmed that the PTPRJ short isoform (named sPTPRJ) is a soluble protein secreted into the supernatant of both endothelial and tumor cells. Like PTPRJ, also sPTPRJ undergoes post-translational modifications such as glycosylation, as assessed by sPTPRJ immunoprecipitation. To characterize its functional activity, we performed an endothelial cell tube formation assay and a wound healing assay on HUVEC cells overexpressing sPTPRJ and we found that sPTPRJ has a proangiogenic activity. We also showed that sPTPRJ expression down-regulates endothelial adhesion molecules, that is a hallmark of proangiogenic activity. Moreover, sPTPRJ mRNA levels in human high-grade glioma, one of the most angiogenic tumors, are higher in tumor samples compared to controls. Further studies will be helpful not only to clarify the way sPTPRJ works but also to supply clues to circumvent its activity in cancer therapy.
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- 2017
40. SGK1 affects RAN/RANBP1/RANGAP1 via SP1 to play a critical role in pre-miRNA nuclear export: a new route of epigenomic regulation
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Giada Catalogna, Rosario Amato, Sante Roperto, Silvia Schenone, Vincenzo Dattilo, Lucia D'Antona, Nicola Perrotti, Mjriam Capula, Rodolfo Iuliano, Cristina Talarico, Cataldo Bianco, Dattilo, V, D'Antona, L, Talarico, C, Capula, M, Catalogna, G, Iuliano, R, Schenone, S, Roperto, Sante, Bianco, C, Perrotti, N, and Amato, R.
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0301 basic medicine ,kinase ,Sp1 Transcription Factor ,Active Transport, Cell Nucleus ,Biology ,Protein Serine-Threonine Kinases ,XPO5 ,epigenomic ,Article ,Cell Line ,Epigenesis, Genetic ,Immediate-Early Proteins ,03 medical and health sciences ,Mice ,microRNA ,medicine ,Animals ,Humans ,SGK1 ,Nuclear export signal ,Drosha ,Cell Nucleus ,Multidisciplinary ,urogenital system ,Nuclear Proteins ,regulation ,Neoplasms, Experimental ,SP1 ,Cell nucleus ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,HEK293 Cells ,ran GTP-Binding Protein ,Tumor progression ,Ran ,Cancer research ,biology.protein ,RAN/RANBP1/RANGAP1 ,SGK1, kinase, RAN/RANBP1/RANGAP1, SP1, epigenomic, regulation ,Neoplasm Transplantation ,Dicer - Abstract
The serum- and glucocorticoid-regulated kinase (SGK1) controls cell transformation and tumor progression. SGK1 affects mitotic stability by regulating the expression of RANBP1/RAN. Here, we demonstrate that SGK1 fluctuations indirectly modify the maturation of pre-miRNAs, by modulating the equilibrium of the RAN/RANBP1/RANGAP1 axis, the main regulator of nucleo-cytoplasmic transport. The levels of pre-miRNAs and mature miRNAs were assessed by qRT-PCR, in total extracts and after differential nuclear/cytoplasmic extraction. RANBP1 expression is the limiting step in the regulation of SGK1-SP1 dependent nuclear export. These results were validated in unrelated tumor models and primary human fibroblasts and corroborated in tumor-engrafted nude mice. The levels of pri-miRNAs, DROSHA, DICER and the compartmental distribution of XPO5 were documented. Experiments using RANGTP conformational antibodies confirmed that SGK1, through RANBP1, decreases the level of the GTP-bound state of RAN. This novel mechanism may play a role in the epigenomic regulation of cell physiology and fate.
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- 2017
41. Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release
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Giorgio Sesti, Giovambattista De Sarro, Francesco Andreozzi, Teresa Procopio, Emilio Russo, Selena Mimmi, Vincenzo Dattilo, Rita Citraro, Giuseppe Fiume, Nicola Perrotti, Andrew Constanti, and Rodolfo Iuliano
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Lipopolysaccharides ,Male ,Immunology ,Pharmacology ,Epileptogenesis ,Neuroprotection ,Behavioral Neuroscience ,chemistry.chemical_compound ,Animals ,Medicine ,Rats, Wistar ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Sickness behavior ,Neuroinflammation ,Depressive Disorder ,Behavior, Animal ,Endocrine and Autonomic Systems ,business.industry ,TOR Serine-Threonine Kinases ,Adenylate Kinase ,Brain ,AMPK ,Electroencephalography ,NF-κB ,Rats ,Disease Models, Animal ,Epilepsy, Absence ,chemistry ,Cytokines ,business ,Proto-Oncogene Proteins c-akt ,Neuroscience ,Signal Transduction - Abstract
The mammalian target of rapamycin (mTOR) pathway has been recently indicated as a suitable drug target for the prevention of epileptogenesis. The mTOR pathway is known for its involvement in the control of the immune system. Since neuroinflammation is recognized as a major contributor to epileptogenesis, we wished to examine whether the neuroprotective effects of mTOR modulation could involve a suppression of the neuroinflammatory process in epileptic brain. We have investigated the early molecular mechanisms involved in the effects of intracerebral administration of the lipopolysaccharide (LPS) in the WAG/Rij rat model of absence epilepsy, in relation to seizure generation and depressive-like behavior; we also tested whether the effects of LPS could be modulated by treatment with rapamycin (RAP), a specific mTOR inhibitor. We determined, in specific rat brain areas, levels of p-mTOR/p-p70S6K and also p-AKT/p-AMPK as downstream or upstream indicators of mTOR activity and tested the effects of LPS and RAP co-administration. Changes in the brain levels of pro-inflammatory cytokines IL-1β and TNF-α and their relative mRNA expression levels were measured, and the involvement of nuclear factor-κB (NF-κB) was also examined in vitro. We confirmed that RAP inhibits the aggravation of absence seizures and depressive-like/sickness behavior induced by LPS in the WAG/Rij rats through the activation of mTOR and show that this effect is correlated with the ability of RAP to dampen and delay LPS increases in neuroinflammatory cytokines IL-1β and TNF-α, most likely through inhibition of the activation of NF-κB. Our results suggest that such a mechanism could contribute to the antiseizure, antiepileptogenic and behavioral effects of RAP and further highlight the potential therapeutic usefulness of mTOR inhibition in the management of human epilepsy and other neurological disorders. Furthermore, we show that LPS-dependent neuroinflammatory effects are also mediated by a complex interplay between AKT, AMPK and mTOR with specificity to selective brain areas. In conclusion, neuroinflammation appears to be a highly coordinated phenomenon, where timing of intervention may be carefully evaluated in order to identify the best suitable target.
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- 2014
42. OC.02.2 DEREGULATION OF SGK1 IN ULCERATIVE COLITIS: A PARADOXICAL RELATIONSHIP BETWEEN IMMUNE CELLS AND COLONIC EPITHELIAL CELLS
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Rocco Spagnuolo, C. Cosco, Lucia D'Antona, Rodolfo Iuliano, Nicola Perrotti, Patrizia Doldo, Giada Catalogna, Rosellina Margherita Mancina, V. Cosco, C. Camassa, Valeria Ventura, Ennio Carbone, Vincenzo Dattilo, Francesco Conforti, Rosario Amato, and Rossana Tallerico
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Immune system ,Hepatology ,business.industry ,Gastroenterology ,medicine ,Cancer research ,SGK1 ,medicine.disease ,business ,Ulcerative colitis - Published
- 2018
43. SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition
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Silvia Schenone, Stefano Alcaro, Cristina Talarico, Rosario Amato, Francesco Ortuso, Nicola Perrotti, Cataldo Bianco, Miranda Menniti, Vincenzo Dattilo, and Lucia D'Antona
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0301 basic medicine ,Physiology ,Drug Resistance ,Cell Cycle Proteins ,Radiation Tolerance ,lcsh:Physiology ,Chemo-resistance ,Radio-resistance ,0302 clinical medicine ,Neoplasms ,lcsh:QD415-436 ,SGK1 ,Caspase ,biology ,lcsh:QP1-981 ,Kinase ,Protein-Serine-Threonine Kinases ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Isoenzymes ,030220 oncology & carcinogenesis ,Caspases ,Mdm2 ,Signal transduction ,Signal Transduction ,MDM2 ,RAN/RANBP1 ,SGK1 inhibitors ,Animals ,Antineoplastic Agents ,Drug Resistance, Neoplasm ,Gamma Rays ,Humans ,Immediate-Early Proteins ,Oxidative Stress ,Transcription Factors ,Protein Serine-Threonine Kinases ,lcsh:Biochemistry ,03 medical and health sciences ,Kinase activity ,Protein kinase B ,Neoplastic ,urogenital system ,030104 developmental biology ,Gene Expression Regulation ,Tumor progression ,biology.protein ,Cancer research ,Neoplasm - Abstract
The serum- and glucocorticoid-regulated kinase (SGK) family consists of three members, SGK1, SGK2 and SGK3, all displaying serine/threonine kinase activity and sharing structural and functional similarities with the AKT family of kinases. SGK1 was originally described as a key enzyme in the hormonal regulation of several ion channels and pumps. Over time, growing and impressive evidence has been accumulated, linking SGK1 to the cell survival, de-differentiation, cell cycle control, regulation of caspases, response to chemical, mechanical and oxidative injury in cancer models as well as to the control of mitotic stability. Much evidence shows that SGK1 is over-expressed in a variety of epithelial tumors. More recently, many contributions to the published literature demonstrate that SGK1 can mediate chemo-and radio-resistance during the treatment of various human tumors, both in vitro and in vivo. SGK1 appears therefore as a dirty player in the stress response to chemical and radio-agents, responsible of a selective advantage that favors the uncontrolled tumor progression and the selection of the most aggressive clones. The purpose of this review is the analysis of the literature describing SGK1 as central node of the cell resistance, and a summary of the possible strategies in the pharmacological targeting of SGK1.
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- 2016
44. Protein tyrosine phosphatase PTPRJ is negatively regulated by microRNA-328
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Camillo Palmieri, Miranda Menniti, Domenico Narciso, Nicola Perrotti, Rodolfo Iuliano, Alfredo Fusco, Francesco Paduano, Eugenio Gaudio, Anna Bilotta, Valter Agosti, Vincenzo Dattilo, and Francesco Trapasso
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Small interfering RNA ,Cell growth ,Response element ,Cell Biology ,Protein tyrosine phosphatase ,Biology ,biology.organism_classification ,Biochemistry ,HeLa ,Downregulation and upregulation ,microRNA ,Cancer research ,Luciferase ,Molecular Biology - Abstract
Expression of PTPRJ, which is a ubiquitous receptor-type protein tyrosine phosphatase, is significantly reduced in a vast majority of human epithelial cancers and cancer cell lines (i.e. colon, lung, thyroid, mammary and pancreatic tumours). A possible role for microRNAs (miRNAs) in the negative regulation of PTPRJ expression has never been investigated. In this study, we show that overexpression of microRNA-328 (miR-328) decreases PTPRJ expression in HeLa and SKBr3 cells. Further investigations demonstrate that miR-328 acts directly on the 3′UTR of PTPRJ, resulting in reduced mRNA levels. Luciferase assay and site-specific mutagenesis were used to identify a functional miRNA response element in the 3′UTR of PTPRJ. Expression of miR-328 significantly enhances cell proliferation in HeLa and SKBr3 cells, similar to the effects of downregulation of PTPRJ with small interfering RNA. Additionally, in HeLa cells, the proliferative effect of miR-328 was not observed when PTPRJ was silenced with small interfering RNA; conversely, restoration of PTPRJ expression in miR-328-overexpressing cells abolished the proliferative activity of miR-328. In conclusion, we report the identification of miR-328 as an important player in the regulation of PTPRJ expression, and we propose that the interaction of miR-328 with PTPRJ is responsible for miR-328-dependent increase of epithelial cell proliferation.
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- 2012
45. Preclinical model in HCC: The SGK1 kinase inhibitor SI113 blocks tumor progression in vitro and in vivo and synergizes with radiotherapy
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Cataldo Bianco, Cristina Talarico, Francesco Gigliotti, Stefano Alcaro, Agnese Barone, Nicola Perrotti, Silvia Schenone, Vincenzo Dattilo, Lorenzo Botta, Claudia Vincenza Fiumara, Giovanni Cuda, Patrizia Lavia, Francesco Ortuso, Paolo Visca, Enzo Gallo, Lucia D'Antona, Marco G. Paggi, Domenica Scumaci, Claudia Abbruzzese, and Rosario Amato
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Proteome ,Apoptosis ,Mice, SCID ,Radiation Tolerance ,Settore CHIM/06 ,Immunoenzyme Techniques ,chemistry.chemical_compound ,Mice ,HCC ,SGK1 ,apoptosis ,kinase inhibitor ,radiotherapy ,Animals ,Blotting, Western ,Carcinoma, Hepatocellular ,Cell Cycle ,Cell Proliferation ,Female ,Gene Expression Regulation, Neoplastic ,Humans ,Immediate-Early Proteins ,In Vitro Techniques ,Liver Neoplasms ,Mice, Inbred NOD ,Protein-Serine-Threonine Kinases ,Pyrazoles ,Pyrimidines ,Tumor Cells, Cultured ,Xenograft Model Antitumor Assays ,Gamma Rays ,Cultured ,Kinase ,Blotting ,Cell cycle ,Tumor Cells ,Oncology ,Paclitaxel ,Western ,Research Paper ,Protein Serine-Threonine Kinases ,SCID ,In vivo ,Kinase inhibitor ,Radiotherapy ,medicine ,Neoplastic transformation ,Neoplastic ,Cell growth ,business.industry ,urogenital system ,Carcinoma ,Cancer ,Hepatocellular ,medicine.disease ,chemistry ,Gene Expression Regulation ,Tumor progression ,Cancer research ,Inbred NOD ,business - Abstract
// Cristina Talarico 1, * , Lucia D’Antona 1, * , Domenica Scumaci 2 , Agnese Barone 2 , Francesco Gigliotti 1 , Claudia Vincenza Fiumara 2 , Vincenzo Dattilo 1 , Enzo Gallo 3 , Paolo Visca 3 , Francesco Ortuso 1 , Claudia Abbruzzese 4 , Lorenzo Botta 5 , Silvia Schenone 6 , Giovanni Cuda 2 , Stefano Alcaro 1 , Cataldo Bianco 2 , Patrizia Lavia 7 , Marco G. Paggi 4 , Nicola Perrotti 1, * , Rosario Amato 1, * 1 Department of “Scienze della Salute”, University “Magna Graecia” of Catanzaro, Viale Europa, Catanzaro, Italy 2 Department of “Medicina Sperimentale e Clinica”, University “Magna Graecia” of Catanzaro, Viale Europa, Catanzaro, Italy 3 Section of Pathology, Regina Elena National Cancer Institute, IRCCS, Rome, Italy 4 Experimental Oncology, Regina Elena National Cancer Institute, IRCCS, Rome, Italy 5 Department of Biotecnologie, Chimica e Farmacia, University of Siena, Siena, Italy 6 Department of Farmacia, University of Genova, Genova, Italy 7 Institute of Molecular Biology and Pathology (IBPM), National Research Council of Italy (CNR), c/o University “La Sapienza”, Rome, Italy * These authors have contributed equally to this work Correspondence to: Rosario Amato, e-mail: rosario.amato@unicz.it Nicola Perrotti, e-mail: perrotti@unicz.it Keywords: SGK1, HCC, kinase inhibitor, radiotherapy, apoptosis Received: June 04, 2015 Accepted: September 28, 2015 Published: October 08, 2015 ABSTRACT The SGK1 kinase is pivotal in signal transduction pathways operating in cell transformation and tumor progression. Here, we characterize in depth a novel potent and selective pyrazolo[3,4-d]pyrimidine-based SGK1 inhibitor. This compound, named SI113, active in vitro in the sub-micromolar range, inhibits SGK1-dependent signaling in cell lines in a dose- and time-dependent manner. We recently showed that SI113 slows down tumor growth and induces cell death in colon carcinoma cells, when used in monotherapy or in combination with paclitaxel. We now demonstrate for the first time that SI113 inhibits tumour growth in hepatocarcinoma models in vitro and in vivo . SI113-dependent tumor inhibition is dose- and time-dependent. In vitro and in vivo SI113-dependent SGK1 inhibition determined a dramatic increase in apotosis/necrosis, inhibited cell proliferation and altered the cell cycle profile of treated cells. Proteome-wide biochemical studies confirmed that SI113 down-regulates the abundance of proteins downstream of SGK1 with established roles in neoplastic transformation, e.g. MDM2, NDRG1 and RAN network members. Consistent with knock-down and over-expressing cellular models for SGK1, SI113 potentiated and synergized with radiotherapy in tumor killing. No short-term toxicity was observed in treated animals during in vivo SI113 administration. These data show that direct SGK1 inhibition can be effective in hepatic cancer therapy, either alone or in combination with radiotherapy.
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- 2015
46. Search for gravitational wave ringdowns from perturbed intermediate mass black holes in LIGO-Virgo data from 2005?2010
- Author
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Li-Wei Wei, Kenneth A. Strain, Fabio Marchesoni, Kyungmin Kim, G. Quiroga, Yi Pan, K. E. Ramirez, Michael L. Gorodetsky, Michaela Pickenpack, Simon Stevenson, David Hammer, Joseph O'Dell, Hartmut Grote, G. Losurdo, Albrecht Ruediger, Neil J. Cornish, Peter Aufmuth, Jiayi Qin, Sammanani S. Premachandra, Jamie Scott, V. Re, Bruce Gendre, Robinjeet Singh, M. Yvert, T. D. Abbott, Jong H. Chow, Ludovico Carbone, P. Couvares, Benno Willke, J. Bauchrowitz, F. Garufi, Cristina Torres, Denis Martynov, S. G. Crowder, Federico Ferrini, Marco Colombini, A. F. Brooks, Q. Chu, Szymon Steplewski, Gerardo Moreno, Chunnong Zhao, J. Macarthur, Karen Roland, G. Vajente, David H. Shoemaker, M. Tse, D. M. Macleod, M. Meinders, W. D. Vousden, Gianpietro Cagnoli, L. Wallace, J. Poeld, R. Frey, Christophe Collette, Zhixing Yang, Evan Ochsner, Vicky Kalogera, Larry R. Price, Elaine Rhoades, Adrien Le Roux, Ajay Kumar, M. Leonardi, Carl Adams, C. Belczynski, M. A. Barton, Alessandra Buonanno, Brian O'Reilly, D. B. Kelley, Matteo Lorenzini, Linqing Wen, S. E. Zuraw, C. Palomba, R. Chakraborty, B. L. Swinkels, D. Verkindt, G. Kang, Christelle Buy, César A. Costa, Xing Zhu, S. Privitera, F. Vetrano, M. K. Haris, T. Vo, C. Bradaschia, P. Oppermann, Michele Vallisneri, M. S. Shahriar, Joris van Heijningen, Sascha Husa, Sonali Mohapatra, P. T. Beyersdorf, Andrew Lundgren, Eliu Huerta, Szabolcs Marka, Timothy A Welborn, M. T. Hartman, V. Kringel, Marica Branchesi, N. Straniero, Alessio Rocchi, D. R. Ingram, Ryan Fisher, Ivan Maksimovic, K. Siellez, A. Conte, Steffen Kaufer, Jo van den Brand, Daniel Amariutei, Saps Buchman, L. Sammut, A. Ain, D. Bersanetti, K. Mailand, K. A. Hodge, Marilyne Andersen, Mauro Tonelli, Kip S. Thorne, T. Chalermsongsak, Alessandro Bertolini, Duncan Meacher, B. Shapiro, Jonathan F. Stebbins, Heinz-Bernd Eggenstein, Zhihui Du, V. P. Mitrofanov, Sanjit Mitra, R. Mittleman, Sharad Gaonkar, Ik Siong Heng, Cyrus Reed, T. Z. Summerscales, Nelson Christensen, Sunil Susmithan, Oliver Puncken, Tyson Littenberg, D. Lodhia, Neil Gehrels, R. Lynch, V. Boschi, Hee Cho, Kasem Mossavi, Deepak Nanda Kumar, Grant David Meadors, R. Coyne, Haixing Miao, S. L. Danilishin, G. Bogaert, M. Shaltev, D. C. Coyne, J. Aasi, Jade Powell, David H. Reitze, Yi-Ming Hu, Sweta Shah, K. Izumi, D. Passuello, Nicolas Leroy, M. Barsuglia, E. O. Lebigot, Vuk Mandic, Alberto Di Lieto, Ignacio Santiago-Prieto, G. Vedovato, W. Katzman, S. E. Dwyer, David Keitel, Richard Gustafson, Suvadeep Bose, Z. Márka, Tomasz Bulik, Alexander Ivanov, C. Affeldt, P. Thomas, Jean-Pierre Zendri, Trevor Sidery, H. Heitmann, Ryan DeRosa, V. Loriette, Francesco Salemi, Pierre-François Cohadon, V. Litvine, Gurumurthy Rajalakshmi, O. Bock, István Rácz, K. L. Dooley, Sabrina D'Antonio, Joshua Yablon, Warren Anderson, Eric K. Gustafson, Sina Koehlenbeck, Jocelyn Read, F. Carbognani, J. Logue, H. J. Bulten, S. Gossler, David Kinzel, Almir Alemic, P. J. Veitch, Amber Stuver, Sanichiro Yoshida, Badri Krishnan, T. P. Bodiya, C. Vorvick, Marc Normandin, Ettore Majorana, Gary McIntyre, M. Edwards, Peter Wessels, Rosa Poggiani, Erik Katsavounidis, Namjun Kim, François Bondu, P. Leaci, A. Colla, Sean Morriss, M. Factourovich, P. Astone, J. Betzwieser, V. Kondrashov, Lisa Barsotti, Bala R. Iyer, Kieran Craig, Shaun Hooper, Valeria Malvezzi, Warren W. Johnson, Jay Marx, Antoine Heidmann, Piotr Jaranowski, Florent Robinet, P. Raffai, Kyle Ryan, Mark Barbet, Samuel Franco, Eric Thrane, Eric W. James, Manasadevi Thirugnanasamba, Sarah Caudill, E. Goetz, Scott Koranda, T. t. Fricke, J. B. Kanner, A. R. Wade, Rainer Weiss, Xu Chen, G. Bergmann, L. Matone, T. Dayanga, Martin van Beuzekom, Les Wade, Irene Di Palma, Young-Min Kim, Albert Lazzarini, Anthony Kremin, Fausto Acernese, Rajesh Kumar, R. J. G. Jonker, H. Overmier, Robert M. S. Schofield, Jessica McIver, Sang Oh, G. Mazzolo, G. Kuehn, D. Barker, K. Wette, F. Ricci, N. Mazumder, R. Quitzow-James, R. Day, Vladimir B. Braginsky, Maik Frede, C. C. Yancey, Giacomo Ciani, A. Mullavey, John J. Oh, D. Sellers, Alastair Grant, N. Morgado, H. Vahlbruch, A. Cumming, C. M. Mow-Lowry, H. Fehrmann, J. Meidam, Lisa M. Goggin, K. Riles, F. Ohme, S. J. Chamberlin, Sergey P. Vyatchanin, Calum Torrie, J. Hanks, J. Y. Vinet, Archana Pai, E. J. King, Hyun Lee, B. P. Abbott, Andrea Moggi, Jean-Daniel Fournier, Rory Smith, Hernan Daveloza, D. Sigg, S. W. Ballmer, Edwin J. Son, D. Ugolini, S. Vass, F. Paoletti, P. Ruggi, J. Eichholz, M. J. Cowart, Keiko Kokeyama, Riccardo Sturani, Andrzej Królak, Laurent Pinard, Fumiko Kawazoe, Tristan Briant, Benjamin William Allen, Stefan Hild, Y. Ma, E. Genin, N. D. Smith-Lefebvre, Graham Woan, Stuart Reid, Steven D. Penn, Yuri Minenkov, Laura Cadonati, Mohana Mageswaran, Veronica Lockett, N. Letendre, Karsten Danzmann, C. Aulbert, R. Cavalieri, Scott Dossa, H. Wittel, Walter Del Pozzo, Riccardo DeSalvo, C. Messenger, Bastian Schulz, R. Vincent-Finley, Jeffery Kline, H. Radkins, J. D. Lough, S. T. Countryman, S. H. Huttner, Fabrice Matichard, W. Kells, Jacob Scheuer, M. Jacobson, M. Weinert, P. Campsie, Michelle E. Walker, J. Birch, Katrin Dahl, A. Libson, M. Punturo, D. Hoak, D. Sentenac, Patrick Brady, Leopoldo Milano, Slawomir Gras, F. Fidecaro, S. Biscans, Fred Raab, Valentina D. Mangano, P. Baker, M. Mantovani, Andrew Melatos, E. Saracco, A. Brillet, Gary Hemming, Michail Agathos, A. Masserot, Santiago Caride, C. L. Mueller, B. Behnke, Matthew Heintze, Richard L. Savage, Alberto Vecchio, G. M. Harry, E. Oelker, K. Venkateswara, Benjamin Aylott, Daniel Kozak, Martina Neri, A. S. Bell, John Miller, T. Prestegard, Charles Celerier, Craig Lawrie, Lee Samuel Finn, Fafhan Feroz, Soma Mukherjee, R. L. McCarthy, Yuri Levin, Thanh Vinh Nguyen, David Blair, Vincenzo Dattilo, E. Coccia, C. Graef, B. A. Weaver, Dmitry Simakov, M. Brinkmann, L. Prokhorov, Will M. Farr, Elisabetta Cesarini, Troy Williams, Neil Gordon, Patrice Hello, Nancy Aggarwal, Robert Stone, Jordan Camp, James S. Clark, M. J. Hart, Richard O'Shaughnessy, B. Barr, Malik Rakhmanov, A. Pasqualetti, Roman Schnabel, J. G. Rollins, F. Y. Khalili, F. Travasso, Michał Bejger, Timo Denker, Luke Williams, J. C. Driggers, L. Austin, A. M. Gretarsson, A. R. Williamson, D. Feldbaum, S. Verma, A. Mytidis, J. E. Brau, L. Martinelli, Susan M. Scott, F. Marion, Efim A. Khazanov, Michael Thomas, A. Effler, Xiaoge Wang, Irene Fiori, G. Ballardin, Moritz Mehmet, David Stops, David Coward, Li Ju, Oleg Palashov, Daniel A. Shaddock, Adam Mercer, A. Basti, Philipp Moesta, Michael Rodruck, A. Allocca, Vincent Dolique, G. Valdes, Walter Winkler, Huan Yang, A. Perreca, M. Drago, B. Hughey, B. J. J. Slagmolen, Sheon Chua, M. Phelps, C. J. Guido, Paul Hopkins, Chiara M. F. Mingarelli, A. S. Markosyan, J. Hanson, Robert Taylor, B. C. Stephens, Mátyás Vasúth, Koji Arai, P. G. Murray, Cody Arceneaux, Fan Zhang, Brian Moe, Guenakh Mitselmakher, Vaibhav Tiwari, Shin Chung, E. Chassande-Mottin, Martin Mohan, Th. Bauer, Michael E Zucker, D. S. Rabeling, Ron Burman, Riccardo Bassiri, Joseph Gleason, V. Fafone, Guido Mueller, Tito Dal Canton, Christophe Michel, Sheila Rowan, Massimiliano Bitossi, Timothy MacDonald, Alan G. Wiseman, K. E. Gushwa, Fabien Kéfélian, E. Maros, J. H. Hough, Rocco Romano, Kendall Ackley, R. K. Nayak, Chad Hanna, M. Kasprzack, Paul Fulda, Ling Kuo, G. Debreczeni, S. E. Gossan, Shane L. Larson, F. Clara, Mary West, F. Magaña-Sandoval, J.-P. Coulon, M. Was, Susanne Milde, A. Staley, H. Vocca, Roy Williams, M. Tacca, Kipp Cannon, Carl-Johan Haster, A. Giazotto, E. Schreiber, Todd Adams, Roland Schilling, Matthew Evans, E. Cuoco, Douglas R. Cook, David Murphy, T. Isogai, R. S. Ottens, Ilaria Nardecchia, Michele Zanolin, S. Doravari, Ilya Mandel, Alex Nitz, Igor Neri, Jaclyn Sanders, J. S. Areeda, V. Sequino, Ruth A. Anderson, P. Kwee, Jeffrey Lewis, Fabrizio Barone, Jesper Munch, Leo Singer, Eugeniy E. Mikhailov, T. J. Massinger, R. Inta, R. W. P. Drever, C. Padilla, I. Ferrante, C. Mishra, J. K. Blackburn, Stephen S. Eikenberry, Innocenzo M. Pinto, J. Marque, Kat Grover, H. J. Jang, K. Haughian, S. Klimenko, Charlotte Bond, I. Kowalska, R. L. Ward, A. L. Lombardi, Corey Gray, M. Heurs, M. Boer, J. Steinlechner, A. S. Sengupta, P. Charlton, Gianluca Gemme, S. C. McGuire, Zsolt Frei, Marine Ducrot, G. D. Hammond, Anatoly Poteomkin, Angie Lin, M. Lormand, Máté Nagy, Sarah Recchia, R. Essick, D. Rosińska, S. P. Tarabrin, P. Puppo, D. Talukder, Nam Gyu Kim, M. Prijatelj, Jan Harms, R. Passaquieti, Marie-Anne Bizouard, G. Manca, Richard A. Matzner, S. Kandhasamy, B. Sorazu, Eric Quintero, J. C. Barayoga, R. Gouaty, Alexander Khalaidovski, E. Macdonald, Anthony Castiglia, Rosario DeRosa, H. Yamamoto, H. R. Paris, G. A. Prodi, John Worden, Alessandra Corsi, Viswanath Bavigadda, Nergis Mavalvala, Francisco Jimenez-Forteza, M. H. Wimmer, J. Greenhalgh, Chris Pankow, Junghyun Lee, F. Piergiovanni, Jerome Degallaix, Chang-Hwan Lee, Giancarlo Cella, A. Kutynia, C. Bogan, Tarun Souradeep, B. Mours, E. J. Daw, A. Gennai, A. Chiummo, F. Nocera, D. J. White, Alicia M. Sintes, Mark Lubinski, Igor Yakushin, M. Davier, J. Prasad, S. Grunewald, Kevin M. McLin, Nary-Catherine Man, Luca Gammaitoni, Andrea Chincarini, Steven Bloemen, Paolo Addesso, K. D. Giardina, M. Razzano, M. Born, D. Buskulic, Virginio Sannibale, David E. McClelland, C. Gill, Angela Di Virgilio, Jonathan R. Gair, Chris Van Den Broeck, N. A. Lockerbie, M. Damjanic, F. Martelli, Michael Smith, Kenneth G. Libbrecht, Husne Dereli, Harald Lueck, F. Cleva, S. Meshkov, S. Farinon, Tjonnie G. F. Li, Eric Howell, Huang-Wei Pan, Gijs Nelemans, T. B. Edo, Thomas Dent, Vladimir Dergachev, Eric D. Black, Jolien D. E. Creighton, Lindy Blackburn, S. Frasca, Michael Landry, James Whelan, P. Ajith, M. Cordier, N. A. Robertson, C. Lazzaro, K. Holt, Alan J. Weinstein, Chunglee Kim, I. A. Bilenko, S. Leavey, Stephen Fairhurst, Juan Calderón Bustillo, M. R. Abernathy, Kema Williams, Peter Fritschel, David J. Ottaway, G. Billingsley, David Hosken, L. Bosi, Peter Kalmus, B. Lantz, J. R. Leong, M. C. Díaz, Philip Graff, Tania Regimbau, Y. Ji, M. M. Hanke, C. Maglione, Ruslan Vaulin, Dirk Schuette, David B. Tanner, Stuart Anderson, T. P. Downes, M. Pedraza, K. Loew, Maria Alessandra Papa, F. Cavalier, M. Pichot, Collin Capano, Matthew Benacquista, Enrico Calloni, G. Traylor, Thomas Corbitt, Gabor Endroczi, Benjamin J. Owen, Gareth S. Davies, W. Z. Korth, Martin Hendry, Christopher Wipf, K. V. Tokmakov, Martin Hewitson, Junwei Cao, Alexander Corpuz, Bernard F. Whiting, Tobias Westphal, David Jones, Stan Whitcomb, Joseph A. Giaime, Marco Cavaglia, Patrick J. Sutton, F. Frasconi, C. R. Ramet, R. Flaminio, Odylio D. Aguiar, Abraham Singer, I. W. Martin, A. W. Heptonstall, Vivien Raymond, Peter R. Saulson, László Gondán, R. Abbott, Erik Luijten, David Nolting, M. C. Araya, Marie Huynh, V. Brisson, Emelie Harstad, Rana X. Adhikari, B. Machenschalk, F. Donovan, Phil Ehrens, L. Naticchioni, Salvatore Vitale, Ryan Goetz, A. L. Urban, Nick Mangini, C. J. Bell, K. Mason, Clive Tomlinson, Anna-Maria A. van Veggel, Sanjeev Dhurandhar, T. Huynh-Dinh, J. S. Kissel, Marc Favata, Roger Jones, R. M. Martin, D. D. Brown, Peter Shawhan, Xavier Siemens, K. Kawabe, S. M. Aston, F. Brückner, Michael W. Coughlin, Romain Bonnand, A. Viceré, T. Etzel, Yi Chen, Peter King, L. Bonelli, J. Slutsky, C. S. Unnikrishnan, Hyung-Mok Lee, Dan Moraru, Samuel Deléglise, Karoline Wiesner, Benjamin Canuel, P. M. Meyers, Sourav Ghosh, Scott Coughlin, J. H. Romie, Imre Bartos, Tom M. Evans, Barry C. Barish, Paul J. Groot, Marc van der Sluys, L. Cunningham, R. Douglas, John Veitch, V. Quetschke, Bangalore Suryanarayana Sathyaprakash, Martin M. Fejer, J. R. Smith, R. Bork, L. R. Cominsky, Axel Donath, Tobias Eberle, M. MacInnis, Gianluca Guidi, S. Raja, S. E. Strigin, Bruce Levine, G. M. Keiser, Benjamin Farr, Christian Cepeda, P. Rapagnani, Andreas Freise, Vincenzo Pierro, Alexander Sergeev, Paul D. Lasky, John Karlen, Joshua L. Willis, J. Zweizig, Carol Wilkinson, Laura Nuttall, G. Mendell, Matthew Pitkin, Liyuan Zhang, M. Wade, Sebastian Steinlechner, C. Osthelder, Karel E. Urbanek, D. O. Bridges, M. Granata, Prayush Kumar, G. P. Newton, M. Fyffe, Gabriela Gonzalez, I. W. Harry, Shiuh Chao, Gleb Romanov, Jim Batch, Adam Zadrozny, M. G. Beker, Qi Fang, V. Necula, Luciano Di Fiore, V. V. Frolov, V. Sandberg, K. A. Thorne, Benoit Sassolas, Stanislav Babak, M. Constancio, Duncan A. Brown, M. Wang, APC - Cosmologie, AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Observatoire de Paris, Université Paris sciences et lettres (PSL), Laboratoire de l'Accélérateur Linéaire (LAL), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Astrophysique Relativiste Théories Expériences Métrologie Instrumentation Signaux (ARTEMIS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des matériaux avancés (LMA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), APC - Gravitation (APC-Gravitation), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Max-Planck-Institut für Gravitationsphysik ( Albert-Einstein-Institut ) (AEI), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), IVC Lab, Lenovo Research, Lenovo, European Synchrotron Radiation Facility (ESRF), Physique Corpusculaire et Cosmologie - Collège de France ( PCC ), Collège de France ( CdF ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -Collège de France ( CdF ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ) -AstroParticule et Cosmologie ( APC - UMR 7164 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Observatoire de Paris-Université Paris Diderot - Paris 7 ( UPD7 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Observatoire de Paris-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire de l'Accélérateur Linéaire ( LAL ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Astrophysique Relativiste Théories Expériences Métrologie Instrumentation Signaux ( ARTEMIS ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Observatoire de la Côte d'Azur, Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Physique de Rennes ( IPR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire des matériaux avancés ( LMA ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Annecy de Physique des Particules ( LAPP/Laboratoire d'Annecy-le-Vieux de Physique des Particules ), Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ), AstroParticule et Cosmologie ( APC - UMR 7164 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Observatoire de Paris-Université Paris Diderot - Paris 7 ( UPD7 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), APC - Gravitation ( APC-Gravitation ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Observatoire de Paris-Université Paris Diderot - Paris 7 ( UPD7 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Observatoire de Paris-Université Paris Diderot - Paris 7 ( UPD7 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Max-Planck-Institut für Gravitationsphysik (Albert-Einstein-Institut), Max-Planck-Institut-Max-Planck-Institut, ESPCI ParisTech, Universitá degli Studi dell’Insubria, European Synchrotron Radiation Facility ( ESRF ), Aasi, J., Abbott, B. P., Abbott, R., Abbott, T., Abernathy, M. R., Acernese, F., Ackley, K., Adams, C., Adams, T., Addesso, P., Adhikari, R. X., Affeldt, C., Agathos, M., Aggarwal, N., Aguiar, O. D., Ain, A., Ajith, P., Alemic, A., Allen, B., Allocca, A., Amariutei, D., Andersen, M., Anderson, R., Anderson, S. B., Anderson, W. G., Arai, K., Araya, M. C., Arceneaux, C., Areeda, J., Aston, S. M., Astone, P., Aufmuth, P., Aulbert, C., Austin, L., Aylott, B. E., Babak, S., Baker, P. T., Ballardin, G., Ballmer, S. W., Barayoga, J. C., Barbet, M., Barish, B. C., Barker, D., Barone, F., Barr, B., Barsotti, L., Barsuglia, M., Barton, M. A., Bartos, I., Bassiri, R., Basti, A., Batch, J. C., Bauchrowitz, J., Bauer, T. h. S., Bavigadda, V., Behnke, B., Bejger, M., Beker, M. G., Belczynski, C., Bell, A. S., Bell, C., Benacquista, M., Bergmann, G., Bersanetti, D., Bertolini, A., Betzwieser, J., Beyersdorf, P. T., Bilenko, I. A., Billingsley, G., Birch, J., Biscans, S., Bitossi, M., Bizouard, M. A., Black, E., Blackburn, J. K., Blackburn, L., Blair, D., Bloemen, S., Bock, O., Bodiya, T. P., Boer, M., Bogaert, G., Bogan, C., Bond, C., Bondu, F., Bonelli, L., Bonnand, R., Bork, R., Born, M., Boschi, V., Sukanta, Bose, Bosi, L., Bradaschia, C., Brady, P. R., Braginsky, V. B., Branchesi, M., Brau, J. E., Briant, T., Bridges, D. O., Brillet, A., Brinkmann, M., Brisson, V., Brooks, A. F., Brown, D. A., Brown, D. D., Brckner, F., Buchman, S., Bulik, T., Bulten, H. J., Buonanno, A., Burman, R., Buskulic, D., Buy, C., Cadonati, L., Cagnoli, G., Caldern Bustillo, J., Calloni, Enrico, Camp, J. B., Campsie, P., Cannon, K. C., Canuel, B., Cao, J., Capano, C. D., Carbognani, F., Carbone, L., Caride, S., Castiglia, A., Caudill, S., Cavagli, M., Cavalier, F., Cavalieri, R., Celerier, C., Cella, G., Cepeda, C., Cesarini, E., Chakraborty, R., Chalermsongsak, T., Chamberlin, S. J., Chao, S., Charlton, P., Chassande Mottin, E., Chen, X., Chen, Y., Chincarini, A., Chiummo, A., Cho, H. S., Chow, J., Christensen, N., Chu, Q., Chua, S. S. Y., Chung, S., Ciani, G., Clara, F., Clark, J. A., Cleva, F., Coccia, E., Cohadon, P. F., Colla, A., Collette, C., Colombini, M., Cominsky, L., Constancio, M., Conte, A., Cook, D., Corbitt, T. R., Cordier, M., Cornish, N., Corpuz, A., Corsi, A., Costa, C. A., Coughlin, M. W., Coughlin, S., Coulon, J. P., Countryman, S., Couvares, P., Coward, D. M., Cowart, M., Coyne, D. C., Coyne, R., Craig, K., Creighton, J. D. E., Crowder, S. G., Cumming, A., Cunningham, L., Cuoco, E., Dahl, K., Dal Canton, T., Damjanic, M., Danilishin, S. L., Dantonio, S., Danzmann, K., Dattilo, V., Daveloza, H., Davier, M., Davies, G. S., Daw, E. J., Day, R., Dayanga, T., Debreczeni, G., Degallaix, J., Delglise, S., Del Pozzo, W., Denker, T., Dent, T., Dereli, H., Dergachev, V., DE ROSA, Rosario, Derosa, R. T., Desalvo, R., Dhurandhar, S., Daz, M., Di Fiore, L., Di Lieto, A., Di Palma, I., Di Virgilio, A., Dolique, V., Donath, A., Donovan, F., Dooley, K. L., Doravari, S., Dossa, S., Douglas, R., Downes, T. P., Drago, M., Drever, R. W. P., Driggers, J. C., Du, Z., Ducrot, M., Dwyer, S., Eberle, T., Edo, T., Edwards, M., Effler, A., Eggenstein, H., Ehrens, P., Eichholz, J., Eikenberry, S. S., Endrczi, G., Essick, R., Etzel, T., Evans, M., Evans, T., Factourovich, M., Fafone, V., Fairhurst, S., Fang, Q., Farinon, S., Farr, B., Farr, W. M., Favata, M., Fehrmann, H., Fejer, M. M., Feldbaum, D., Feroz, F., Ferrante, I., Ferrini, F., Fidecaro, F., Finn, L. S., Fiori, I., Fisher, R. P., Flaminio, R., Fournier, J. D., Franco, S., Frasca, S., Frasconi, F., Frede, M., Frei, Z., Freise, A., Frey, R., Fricke, T. T., Fritschel, P., Frolov, V. V., Fulda, P., Fyffe, M., Gair, J., Gammaitoni, L., Gaonkar, S., Garufi, Fabio, Gehrels, N., Gemme, G., Gendre, B., Genin, E., Gennai, A., Ghosh, S., Giaime, J. A., Giardina, K. D., Giazotto, A., Gill, C., Gleason, J., Goetz, E., Goetz, R., Goggin, L. M., Gondan, L., Gonzlez, G., Gordon, N., Gorodetsky, M. L., Gossan, S., Goler, S., Gouaty, R., Grf, C., Graff, P. B., Granata, M., Grant, A., Gras, S., Gray, C., Greenhalgh, R. J. S., Gretarsson, A. M., Groot, P., Grote, H., Grover, K., Grunewald, S., Guidi, G. M., Guido, C., Gushwa, K., Gustafson, E. K., Gustafson, R., Hammer, D., Hammond, G., Hanke, M., Hanks, J., Hanna, C., Hanson, J., Harms, J., Harry, G. M., Harry, I. W., Harstad, E. D., Hart, M., Hartman, M. T., Haster, C. J., Haughian, K., Heidmann, A., Heintze, M., Heitmann, H., Hello, P., Hemming, G., Hendry, M., Heng, I. S., Heptonstall, A. W., Heurs, M., Hewitson, M., Hild, S., Hoak, D., Hodge, K. A., Holt, K., Hooper, S., Hopkins, P., Hosken, D. J., Hough, J., Howell, E. J., Hu, Y., Huerta, E., Hughey, B., Husa, S., Huttner, S. H., Huynh, M., Huynh Dinh, T., Ingram, D. R., Inta, R., Isogai, T., Ivanov, A., Iyer, B. R., Izumi, K., Jacobson, M., James, E., Jang, H., Jaranowski, P., Ji, Y., Jimnez Forteza, F., Johnson, W. W., Jones, D. I., Jones, R., Jonker, R. J. G., Ju, L., Haris, K, Kalmus, P., Kalogera, V., Kandhasamy, S., Kang, G., Kanner, J. B., Karlen, J., Kasprzack, M., Katsavounidis, E., Katzman, W., Kaufer, H., Kawabe, K., Kawazoe, F., Kflian, F., Keiser, G. M., Keitel, D., Kelley, D. B., Kells, W., Khalaidovski, A., Khalili, F. Y., Khazanov, E. A., Kim, C., Kim, K., Kim, N., Kim, N. G., Kim, Y. M., King, E. J., King, P. J., Kinzel, D. L., Kissel, J. S., Klimenko, S., Kline, J., Koehlenbeck, S., Kokeyama, K., Kondrashov, V., Koranda, S., Korth, W. Z., Kowalska, I., Kozak, D. B., Kremin, A., Kringel, V., Krishnan, B., Krlak, A., Kuehn, G., Kumar, A., Nanda Kumar, D., Kumar, P., Kumar, R., Kuo, L., Kutynia, A., Kwee, P., Landry, M., Lantz, B., Larson, S., Lasky, P. D., Lawrie, C., Lazzarini, A., Lazzaro, C., Leaci, P., Leavey, S., Lebigot, E. O., Lee, C. H., Lee, H. K., Lee, H. M., Lee, J., Leonardi, M., Leong, J. R., Le Roux, A., Leroy, N., Letendre, N., Levin, Y., Levine, B., Lewis, J., T. G. F., Li, Libbrecht, K., Libson, A., Lin, A. C., Littenberg, T. B., Litvine, V., Lockerbie, N. A., Lockett, V., Lodhia, D., Loew, K., Logue, J., Lombardi, A. L., Lorenzini, M., Loriette, V., Lormand, M., Losurdo, G., Lough, J., Lubinski, M. J., Lck, H., Luijten, E., Lundgren, A. P., Lynch, R., Ma, Y., Macarthur, J., Macdonald, E. P., Macdonald, T., Machenschalk, B., Macinnis, M., Macleod, D. M., Magana Sandoval, F., Mageswaran, M., Maglione, C., Mailand, K., Majorana, E., Maksimovic, I., Malvezzi, V., Man, N., Manca, G. M., Mandel, I., Mandic, V., Mangano, V., Mangini, N., Mantovani, M., Marchesoni, F., Marion, F., Mrka, S., Mrka, Z., Markosyan, A., Maros, E., Marque, J., Martelli, F., Martin, I. W., Martin, R. M., Martinelli, L., Martynov, D., Marx, J. N., Mason, K., Masserot, A., Massinger, T. J., Matichard, F., Matone, L., Matzner, R. A., Mavalvala, N., Mazumder, N., Mazzolo, G., Mccarthy, R., Mcclelland, D. E., Mcguire, S. C., Mcintyre, G., Mciver, J., Mclin, K., Meacher, D., Meadors, G. 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G., Romano, R., Romanov, G., Romie, J. H., Rosiska, D., Rowan, S., Rdiger, A., Ruggi, P., Ryan, K., Salemi, F., Sammut, L., Sandberg, V., Sanders, J. R., Sannibale, V., Santiago Prieto, I., Saracco, E., Sassolas, B., Sathyaprakash, B. S., Saulson, P. R., Savage, R., Scheuer, J., Schilling, R., Schnabel, R., Schofield, R. M. S., Schreiber, E., Schuette, D., Schutz, B. F., Scott, J., Scott, S. M., Sellers, D., Sengupta, A. S., Sentenac, D., Sequino, V., Sergeev, A., Shaddock, D., Shah, S., Shahriar, M. S., Shaltev, M., Shapiro, B., Shawhan, P., Shoemaker, D. H., Sidery, T. L., Siellez, K., Siemens, X., Sigg, D., Simakov, D., Singer, A., Singer, L., Singh, R., Sintes, A. M., Slagmolen, B. J. J., Slutsky, J., Smith, J. R., Smith, M., Smith, R. J. E., Smith Lefebvre, N. D., Son, E. J., Sorazu, B., Souradeep, T., Staley, A., Stebbins, J., Steinlechner, J., Steinlechner, S., Stephens, B. C., Steplewski, S., Stevenson, S., Stone, R., Stops, D., Strain, K. A., Straniero, N., Strigin, S., Sturani, R., Stuver, A. L., Summerscales, T. Z., Susmithan, S., Sutton, P. J., Swinkels, B., Tacca, M., Talukder, D., Tanner, D. B., Tarabrin, S. P., Taylor, R., Thirugnanasambandam, M. P., Thomas, M., Thomas, P., Thorne, K. A., Thorne, K. S., Thrane, E., Tiwari, V., Tokmakov, K. V., Tomlinson, C., Tonelli, M., Torres, C. V., Torrie, C. I., Travasso, F., Traylor, G., Tse, M., Ugolini, D., Unnikrishnan, C. S., Urban, A. L., Urbanek, K., Vahlbruch, H., Vajente, G., Valdes, G., Vallisneri, M., van Beuzekom, M., van den Brand, J. F. J., Van Den Broeck, C., van der Sluys, M. V., van Heijningen, J., van Veggel, A. A., Vass, S., Vasth, M., Vaulin, R., Vecchio, A., Vedovato, G., Veitch, J., Veitch, P. J., Venkateswara, K., Verkindt, D., Verma, S. S., Vetrano, F., Vicer, A., Vincent Finley, R., Vinet, J. Y., Vitale, S., Vo, T., Vocca, H., Vorvick, C., Vousden, W. D., Vyachanin, S. P., Wade, A., Wade, L., Wade, M., Walker, M., Wallace, L., Wang, M., Wang, X., Ward, R. L., Was, M., Weaver, B., Wei, L. W., Weinert, M., Weinstein, A. J., Weiss, R., Welborn, T., Wen, L., Wessels, P., West, M., Westphal, T., Wette, K., Whelan, J. T., Whitcomb, S. E., White, D. J., Whiting, B. F., Wiesner, K., Wilkinson, C., Williams, K., Williams, L., Williams, R., Williams, T., Williamson, A. R., Willis, J. L., Willke, B., Wimmer, M., Winkler, W., Wipf, C. C., Wiseman, A. G., Wittel, H., Woan, G., Worden, J., Yablon, J., Yakushin, I., Yamamoto, H., Yancey, C. C., Yang, H., Yang, Z., Yoshida, S., Yvert, M., Zadrony, A., Zanolin, M., Zendri, J. P., Fan, Zhang, Zhang, L., Zhao, C., Zhu, X. J., Zucker, M. E., Zuraw, S., Zweizig, J., Pinto, Innocenzo, Physique Corpusculaire et Cosmologie - Collège de France (PCC), Collège de France (CdF)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-AstroParticule et Cosmologie (APC (UMR_7164)), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Annecy de Physique des Particules (LAPP/Laboratoire d'Annecy-le-Vieux de Physique des Particules), PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Max-Planck-Institut für Gravitationsphysik ( Albert-Einstein-Institut ) (AEI), (Astro)-Particles Physics, The LIGO Scientific Collaboration, The Virgo Collaboration, LIGO, California Institute of Technology, Louisiana State University, INFN, Sezione di Napoli, Complesso Universitario di Monte S. 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- Subjects
SPACE-TELESCOPE EVIDENCE ,Physics and Astronomy (miscellaneous) ,Astronomy ,Pacs number: 04.70.-s ,Astrophysics ,01 natural sciences ,Pacs number: 04.80.Nn ,General Relativity and Quantum Cosmology ,Gravitation ,GLOBULAR-CLUSTER M15 ,Gravitational waves ,black holes ,interferometer ,CORE ,Quantum Cosmology ,gravitational wave ,010303 astronomy & astrophysics ,EQUATIONS ,QC ,QB ,Physics ,Pacs number: 07.05.Kf ,Oscillation ,Settore FIS/01 - Fisica Sperimentale ,CANDIDATE ,Nuclear and High Energy Physics ,PERTURBATIONS ,Pacs number: 95.85.Sz ,[PHYS.GRQC]Physics [physics]/General Relativity and Quantum Cosmology [gr-qc] ,Gravitational wave ,General Relativity ,Stellar mass ,General relativity ,MERGERS ,Astrophysics::High Energy Astrophysical Phenomena ,FOS: Physical sciences ,General Relativity and Quantum Cosmology (gr-qc) ,Astrophysics::Cosmology and Extragalactic Astrophysics ,[ PHYS.GRQC ] Physics [physics]/General Relativity and Quantum Cosmology [gr-qc] ,Settore FIS/05 - Astronomia e Astrofisica ,0103 physical sciences ,FIELD ,COLLAPSE ,Astrophysics::Galaxy Astrophysics ,010308 nuclear & particles physics ,BINARY ,Mass ratio ,LIGO ,13. Climate action ,Globular cluster ,[PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph] - Abstract
We report results from a search for gravitational waves produced by perturbed intermediate mass black holes (IMBH) in data collected by LIGO and Virgo between 2005 and 2010. The search was sensitive to astrophysical sources that produced damped sinusoid gravitational wave signals, also known as ringdowns, with frequency $50\le f_{0}/\mathrm{Hz} \le 2000$ and decay timescale $0.0001\lesssim \tau/\mathrm{s} \lesssim 0.1$ characteristic of those produced in mergers of IMBH pairs. No significant gravitational wave candidate was detected. We report upper limits on the astrophysical coalescence rates of IMBHs with total binary mass $50 \le M/\mathrm{M}_\odot \le 450$ and component mass ratios of either 1:1 or 4:1. For systems with total mass $100 \le M/\mathrm{M}_\odot \le 150$, we report a 90%-confidence upper limit on the rate of binary IMBH mergers with non-spinning and equal mass components of $6.9\times10^{-8}\,$Mpc$^{-3}$yr$^{-1}$. We also report a rate upper limit for ringdown waveforms from perturbed IMBHs, radiating 1% of their mass as gravitational waves in the fundamental, $\ell=m=2$, oscillation mode, that is nearly three orders of magnitude more stringent than previous results., Comment: for the science summary, see http://www.ligo.org/science/Publication-S5S6RD/index.php
- Published
- 2014
47. Discovery of PTPRJ Agonist Peptides That Effectively Inhibit in Vitro Cancer Cell Proliferation and Tube Formation
- Author
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Francesco Ortuso, Rodolfo Iuliano, Francesco Trapasso, Alfonso Carotenuto, Anna Artese, Isabel Gomez-Monterrey, Ermelinda Vernieri, Nicola Perrotti, Alessia Bertamino, Francesco Paduano, Pietro Campiglia, Ettore Novellino, Carlo M. Croce, Alfredo Fusco, Stefano Alcaro, Diego Brancaccio, Eugenio Gaudio, Anna Bilotta, Paolo Grieco, Vincenzo Dattilo, Marina Sala, Simona Musella, F., Ortuso, F., Paduano, Carotenuto, Alfonso, GOMEZ MONTERREY, ISABEL MARIA, A., Bilotta, E., Gaudio, M., Sala, A., Artese, E., Vernieri, V., Dattilo, R., Iuliano, Brancaccio, Diego, A., Bertamino, S., Musella, S., Alcaro, Grieco, Paolo, N., Perrotti, C. M., Croce, Novellino, Ettore, Fusco, Alfredo, P., Campiglia, and F., Trapasso
- Subjects
Models, Molecular ,Protein Folding ,Magnetic Resonance Spectroscopy ,Antineoplastic Agents ,Apoptosis ,Breast Neoplasms ,Biology ,Biochemistry ,Cell Line ,HeLa ,PTPRJ agonist peptide ,Humans ,Amino Acid Sequence ,Cell Proliferation ,Tube formation ,Matrigel ,Cell growth ,Receptor-Like Protein Tyrosine Phosphatases, Class 3 ,General Medicine ,cancer cell proliferation ,biology.organism_classification ,Molecular biology ,In vitro ,Cell biology ,SKBR3 ,Cell culture ,Molecular Medicine ,Female ,Peptides ,Monte Carlo Method ,Oligopeptides ,HeLa Cells - Abstract
PTPRJ is a receptor protein tyrosine phospha- tase involved in both physiological and oncogenic pathways. We previously reported that its expression is strongly reduced in the majority of explored cancer cell lines and tumor samples; moreover, its restoration blocks in vitro cancer cell proliferation and in vivo tumor formation. By means of a phage display library screening, we recently identified two peptides able to bind and activate PTPRJ, resulting in cell growth inhibition and apoptosis of both cancer and endothelial cells. Here, on a previously discovered PTPRJ agonist peptide, PTPRJ-pep19, we synthe- sized and assayed a panel of nonapeptide analogues with the aim to identify specific amino acid residues responsible for peptide activity. These second-generation nonapeptides were tested on both cancer and primary endothelial cells (HeLa and HUVEC, respectively); interestingly, one of them (PTPRJ-19.4) was able to both dramatically reduce cell proliferation and effectively trigger apoptosis of both HeLa and HUVECs compared to its first-generation counterpart. Moreover, PTPRJ-pep19.4 significantly inhibited in vitro tube formation on Matrigel. Intriguingly, while ERK1/2 phosphorylation and cell proliferation were both inhibited by PTPRJ-pep19.4 in breast cancer cells (MCF-7 and SKBr3), no effects were observed on primary normal human mammary endothelial cells (HMEC). We further characterized these peptides by molecular modeling and NMR experiments reporting, for the most active peptide, the possibility of self-aggregation states and highlighting new hints of structure−activity relationship. Thus, our results indicate that this nonapeptide might represent a great potential lead for the development of novel targeted anticancer drugs.
- Published
- 2013
48. Retraction Statement. Paper by Li J, Yu J, Zhang H, Wang B, GuoH, Bai J, Wang J, Dong Y, Zhao Y., Wang Y., entitled ‘Exosomes-Derived MiR-302b Suppresses Lung Cancer Cell Proliferation and Migration via TGFβRII Inhibition‘ Cell Physiol Biochem 2016;38(5):1715-1726. doi:10.1159/000443111
- Author
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Ping Lin, Na Cui, Chao-Peng Li, Huanhai Liu, Emi Kurosawa, Yaping Xu, Di Wu, Yin Cheng, Xiaohui Xu, Qingwei Wen, Fandong Meng, Baoxi Zhang, Richard D. Magie, Yueqing Jiang, Luo Xu, Bo Zhai, Sarah J. Matches, Xiaolong Kong, Kazuhisa Ouhara, Peng Zhou, Xiaorong Hu, Huixia Wang, Tao Jiang, Shenyi Jiang, Lijun Hao, Xiu-Ming Liu, Chao Liu, Masahiro Tanaka, Salome Asanidze, Jianbo Wu, Xin Tian, Zohreh Hosseinzadeh, Jens Zierle, Lei Cai, Aimin Yang, Rui Liu, Fangxing Ye, Junhui He, Bu-Chun Zhang, Lars Kaestner, Jianxin Ye, Sara Y. Brucker, Qinyi Liu, Xuefei Wang, Lei Yang, Hidemi Kurihara, Yoshiko Onozawa, Yuki Hirota-Takahata, Futian Ma, W. Paul Bowman, Chaonan Li, Guimin Hao, Zhansong Zhou, Ying Li, Renbin Huang, Yu Ding, Thithaihoa Pham, Ting Deng, Wenhao Shen, Tong-Da Xu, Yi Xiong, Nusrath Habiba, Feifei Xuan, Qiong Deng, Peng He, Yuandong Zhu, Huan Du, Xiaodong Li, Jian Jiang, Yaozong Yuan, Yong Shang, Zhuojun Zheng, Yingzhi Liu, Xiaobao Xie, Xue Cao, Dawei Ge, Hongyi Liu, Liyu Chen, Florian Lang, Nagla Mohamed, Jun Que, Katsuhiro Takeda, Lei Jiang, Yogesh Singh, Susan Franks, De-Feng Pan, Zoe Webster, Fabrizio Carta, Gerolf Gros, Zhiwen Chen, Pengyuan Zheng, Boya Zhang, Miranda Menniti, Zuolei Chen, Jan Hegermann, Juntian Lang, Lianjiang Zhang, Yifan Li, Qiang Huang, Yurong Tan, Jun Wen, Wei Zheng, Jie Xu, Jan J. Brosens, Shugang Yang, Zhaoyu Zhong, Lucia D'Antona, Shuang Ding, Jinzhou Wang, Hongli Jiang, Jiayuan Kou, Xu Wang, Xinyu Xu, Haibin Liu, Baohua Cheng, Haibo Wang, Qiuqiao Xie, Meitong Liu, Francesco Ortuso, Xuesong Li, Yehua Wang, Yongjian Huang, Dong-Ye Li, Xuewei Zhang, Dongmei Yu, Jing Sun, Jennifer H. Steel, Jun Chiba, Riyaz Basha, Qianqian Sun, Judy Mutua, Yonglong Zhang, Hongming Guo, Tetsuya Yoshimoto, Shiguo Liu, Jichun Wang, Zhong Yin, Benjamin Hanf, Xueqi Li, Donat R. Spahn, Qiuying Li, Zhongkai Liu, Liye Fu, Changhong Li, Mariela Arias-Hidalgo, Jian Yuan, Jiabao Zhang, Hideki Kobayashi, Yujie Chen, Claudiu T. Supuran, Xiaoli Wu, Duc Bach Nguyen, Chengyu Wang, Aiqin Li, Shundong Dai, Mikihito Kajiya, Mehrdad Ghashghaeinia, Etheresia Pretorius, Stefano Alcaro, Ni Qin, Wei Wang, Yueming Xu, Shijun Zhang, Vincenzo Dattilo, Hu Peng, Cheng Liu, Ruisong Ma, Chunfeng Yi, Xiaojun Tang, Xianfeng Yu, Rosario Amato, Cong-Wei Zhang, Xuefei Li, Yi Ba, Lingfang Li, Junxuan Chang, Chunxia Chen, Lei Chen, Ji Zheng, Hongyuan Xia, Shane Fernando, Bao-ping Yu, Madhuri S. Salker, Yong Liu, Jingping Fan, Guojun Wu, Yating Tang, Bao Nguyen, Weipan Xu, Cheng Wang, Jianchun Liao, Sai Luo, Liming Yang, Yanfeng Liu, Cataldo Bianco, Chenyu Zhang, Yan Gao, Akihiro Tamura, Qi Fan, Wansu Huang, Mauro C. Wesseling, Yan Yang, Xiao Li, Kimberly G. Fulda, Hao Jiang, Yang Wang, Jie Zhang, Juman Li, Shu-Guang Song, Huiyu Liu, Jeanette N. du Plooy, Ban Liu, Zhijun Sun, Le Tao, Silvia Schenone, Deep Shah, Bo Fu, Volker Endeward, Wei Zhang, Xiaojian Cao, Huijie Gao, Hong Jiang, Ingolf Bernhardt, Yi Lu, Xiaozhou Zhou, Georgios Tsiavaliaris, Dan Li, Yingbin Ge, Youhong Jiang, Ning Chen, Bing Wang, Weiyan Yao, Janette Bester, Lisa Wagner-Britz, Chunfeng He, Guangwei Zhu, Jinfu Zhuang, Deyong Zhao, Shinji Matsuda, Cristina Talarico, Zhen-peng Huang, Dongying Xue, Gensheng Lu, Nicola Perrotti, Tsuyoshi Fujita, Jinhong Pan, Chengguang Sui, Yan Li, Jia Su, Toru Hasegawa, Xiaojie Wei, Rosi Bissinger, Zhennan Zhao, Xiaoqing Zhao, Hu Qiu, Haichen Chu, Lingling Wu, Jianchun Huang, Jin Hua, Shuiping Liu, Longbin Zheng, Weiying Gu, Xiangmei Chen, Jaya Nautiyal, Jingting Jiang, Wenting Ma, Xuefeng Sun, Chunni Zhang, Yoko Ishimoto, Yi Zhi, Guoqiang Zhao, Xuefeng Feng, Ye Tian, Ruirui Han, Jian Tang, Yang Lu, Ziyu Dai, Tao Sui, Yuko Iwadate, Haruka Imai, Wen-Qi Wang, Zhongni Liu, Jin Yang, Lili Wang, and Na Liu
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Lung cancer cell ,Physiology ,Chemistry ,030220 oncology & carcinogenesis ,Cell ,medicine ,Molecular biology ,Microvesicles - Published
- 2016
49. Protein tyrosine phosphatase PTPRJ is negatively regulated by microRNA-328
- Author
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Francesco, Paduano, Vincenzo, Dattilo, Domenico, Narciso, Anna, Bilotta, Eugenio, Gaudio, Miranda, Menniti, Valter, Agosti, Camillo, Palmieri, Nicola, Perrotti, Alfredo, Fusco, Francesco, Trapasso, and Rodolfo, Iuliano
- Subjects
Analysis of Variance ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Blotting, Western ,Receptor-Like Protein Tyrosine Phosphatases, Class 3 ,Down-Regulation ,Response Elements ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cell Movement ,Cell Line, Tumor ,Sequence Homology, Nucleic Acid ,Mutagenesis, Site-Directed ,Humans ,RNA Interference ,Luciferases ,3' Untranslated Regions ,Cell Proliferation ,HeLa Cells - Abstract
Expression of PTPRJ, which is a ubiquitous receptor-type protein tyrosine phosphatase, is significantly reduced in a vast majority of human epithelial cancers and cancer cell lines (i.e. colon, lung, thyroid, mammary and pancreatic tumours). A possible role for microRNAs (miRNAs) in the negative regulation of PTPRJ expression has never been investigated. In this study, we show that overexpression of microRNA-328 (miR-328) decreases PTPRJ expression in HeLa and SKBr3 cells. Further investigations demonstrate that miR-328 acts directly on the 3'UTR of PTPRJ, resulting in reduced mRNA levels. Luciferase assay and site-specific mutagenesis were used to identify a functional miRNA response element in the 3'UTR of PTPRJ. Expression of miR-328 significantly enhances cell proliferation in HeLa and SKBr3 cells, similar to the effects of downregulation of PTPRJ with small interfering RNA. Additionally, in HeLa cells, the proliferative effect of miR-328 was not observed when PTPRJ was silenced with small interfering RNA; conversely, restoration of PTPRJ expression in miR-328-overexpressing cells abolished the proliferative activity of miR-328. In conclusion, we report the identification of miR-328 as an important player in the regulation of PTPRJ expression, and we propose that the interaction of miR-328 with PTPRJ is responsible for miR-328-dependent increase of epithelial cell proliferation.
- Published
- 2012
50. The role of microRNAs in cancer susceptibility
- Author
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Francesco Trapasso, Nicola Perrotti, Rodolfo Iuliano, Marco Flavio Michele Vismara, Francesco Baudi, and Vincenzo Dattilo
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Untranslated region ,Genetics and Molecular Biology (all) ,3' Untranslated Regions ,Binding Sites ,Genome, Human ,Humans ,MicroRNAs ,Mutation ,Neoplasms ,Genetic Predisposition to Disease ,Biochemistry, Genetics and Molecular Biology (all) ,Immunology and Microbiology (all) ,lcsh:Medicine ,Single-nucleotide polymorphism ,Review Article ,Biology ,medicine.disease_cause ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,microRNA ,medicine ,Gene ,Genetics ,Genome ,General Immunology and Microbiology ,Three prime untranslated region ,lcsh:R ,Cancer ,General Medicine ,medicine.disease ,Human genome ,Human - Abstract
Single nucleotide polymorphisms (SNPs) are germline variations interspersed in the human genome. These subtle changes of DNA sequence can influence the susceptibility to various pathologies including cancer. The functional meaning of SNPs is not always clear, being, the majority of them, localized in noncoding regions. The discovery of microRNAs, tiny noncoding RNAs able to bind the 3′ untranslated region (UTR) of target genes and to consequently downregulate their expression, has provided a functional explanation of how some SNPs positioned in noncoding regions contribute to cancer susceptibility. In this paper we summarize the current knowledge of the effect on cancer susceptibility of SNPs included in regions related with miRNA-dependent pathways. Hereditary cancer comes up from mutations that occur in high-penetrant predisposing tumor genes. However, a considerable part of inherited cancers arises from multiple low-penetrant predisposing gene variants that influence the behavior of cancer insurgence. Despite the established significance of such polymorphic variants in cancer predisposition, sometimes their functional role remains unknown. The discovery of a new group of genes called microRNAs (miRNAs) opened an avenue for the functional interpretation of polymorphisms involved in cancer predisposition.
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