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Pre-clinical

Novel HDAC inhibitors exhibit pre-clinical efficacy in lymphoma models and point to the importance of CDKN1A expression levels in mediating their anti-tumor response.
Authors:Mensah AA, Kwee I, Gaudio E, Rinaldi A, Ponzoni M, Cascione L, Fossati G, Stathis A, Zucca E, Caprini G, Bertoni F.
Source:Oncotarget. 2015 Mar 10;6(7):5059-71.
Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo.
Authors:Li S, Fossati G, Marchetti C, Modena D, Pozzi P, Reznikov LL, Moras ML, Azam T, Abbate A, Mascagni P, Dinarello CA.
Source:J Biol Chem. 2015 Jan 23;290(4):2368-78. doi: 10.1074/jbc.M114.618454. Epub 2014 Dec 1.
Modulation of gamma globin genes expression by histone deacetylase inhibitors: an in vitro study.
Authors:Ronzoni L, Sonzogni L, Fossati G, Modena D, Trombetta E, Porretti L, Cappellini MD.
Source:Br J Haematol. 2014 Jun;165(5):714-21. doi: 10.1111/bjh.12814. Epub 2014 Mar 7.
Histone deacetylase inhibitors modulate interleukin 6-dependent CD4+ T cell polarization in vitro and in vivo.
Authors:Glauben R, Sonnenberg E, Wetzel M, Mascagni P, Siegmund B.
Source:J Biol Chem. 2014 Feb 28;289(9):6142-51. doi: 10.1074/jbc.M113.517599. Epub 2014 Jan 13.
Lysine deacetylase inhibition prevents diabetes by chromatin-independent immunoregulation and ß-cell protection.
Authors:Christensen DP, Gysemans C, Lundh M, Dahllöf MS, Noesgaard D, Schmidt SF, Mandrup S, Birkbak N, Workman CT, Piemonti L, Blaabjerg L, Monzani V, Fossati G, Mascagni P, Paraskevas S, Aikin RA, Billestrup N, Grunnet LG, Dinarello CA, Mathieu C, Mandrup-Poulsen T.
Source:Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1055-9. doi: 10.1073/pnas.1320850111. Epub 2014 Jan 6.
Preclinical studies in the mdx mouse model of duchenne muscular dystrophy with the histone deacetylase inhibitor givinostat.
Authors:Consalvi S, Mozzetta C, Bettica P, Germani M, Fiorentini F, Del Bene F, Rocchetti M, Leoni F, Monzani V, Mascagni P, Puri PL, Saccone V.
Source:Mol Med. 2013 May 20;19:79-87. doi: 10.2119/molmed.2013.00011.
Givinostat and hydroxyurea synergize in vitro to induce apoptosis of cells from JAK2(V617F) myeloproliferative neoplasm patients.
Authors:Amaru Calzada A, Pedrini O, Finazzi G, Leoni F, Mascagni P, Introna M, Rambaldi A, Golay J; Associazione Italiana per la Ricerca sul Cancro-Gruppo Italiano Malattie Mieloproliferative Investigators.
Source:Exp Hematol. 2013 Mar;41(3):253-60.e2. doi: 10.1016/j.exphem.2012.10.013. Epub 2012 Oct 27.
The lysine deacetylase inhibitor Givinostat inhibits ß-cell IL-1ß induced IL-1ß transcription and processing.
Authors:Dahllöf MS, Christensen DP, Lundh M, Dinarello CA, Mascagni P, Grunnet LG, Mandrup-Poulse.
Source:T. Islets. 2012 Nov-Dec;4(6):417-22. doi: 10.4161/isl.23541.
Histone deacetylases 1 and 3 but not 2 mediate cytokine-induced beta cell apoptosis in INS-1 cells and dispersed primary islets from rats and are differentially regulated in the islets of type 1 diabetic children.
Authors:Lundh M, Christensen DP, Damgaard Nielsen M, Richardson SJ, Dahllöf MS, Skovgaard T, Berthelsen J, Dinarello CA, Stevenazzi A, Mascagni P, Grunnet LG, Morgan NG, Mandrup-Poulsen T.
Source:Diabetologia. 2012 Sep;55(9):2421-31. doi: 10.1007/s00125-012-2615-0. Epub 2012 Jul 7.
Functional consequences of inhibiting exocytosis of Weibel-Palade bodies in acute renal ischemia.
Authors:Yasuda K, Vasko R, Hayek P, Ratliff B, Bicer H, Mares J, Maruyama S, Bertuglia S, Mascagni P, Goligorsky MS.
Source:Am J Physiol Renal Physiol. 2012 Mar 15;302(6):F713-21. doi: 10.1152/ajprenal.00541.2011. Epub 2011 Dec 7.
Histone deacetylase inhibitors for treating a spectrum of diseases not related to cancer.
Authors:Dinarello CA, Fossati G, Mascagni P.
Source:Mol Med. 2011 May-Jun;17(5-6):333-52. doi: 10.2119/molmed.2011.00116. Epub 2011 May 5.
The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo.
Authors:Leoni F, Fossati G, Lewis EC, Lee JK, Porro G, Pagani P, Modena D, Moras ML, Pozzi P, Reznikov LL, Siegmund B, Fantuzzi G, Dinarello CA, Mascagni P.
Source:Mol Med. 2005 Jan-Dec;11(1-12):1-15.
Inhibition of HDAC activity by ITF2357 ameliorates joint inflammation and prevents cartilage and bone destruction in experimental arthritis.
Authors:Joosten LA, Leoni F, Meghji S, Mascagni P.
Source:Mol Med. 2011 May-Jun;17(5-6):391-6. doi: 10.2119/molmed.2011.00058. Epub 2011 Feb 11.
The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines.
Authors:Leoni F, Zaliani A, Bertolini G, Porro G, Pagani P, Pozzi P, Donà G, Fossati G, Sozzani S, Azam T, Bufler P, Fantuzzi G, Goncharov I, Kim SH, Pomerantz BJ, Reznikov LL, Siegmund B, Dinarello CA, Mascagni P.
Source:Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2995-3000. Epub 2002 Feb 26.
ITF1697, a stable Lys-Pro-containing peptide, inhibits weibel-palade body exocytosis induced by ischemia/reperfusion and pressure elevation.
Authors:Bertuglia S, Ichimura H, Fossati G, Parthasarathi K, Leoni F, Modena D, Cremonesi P, Bhattacharya J, Mascagni P.
Source:Mol Med. 2007 Nov-Dec;13(11-12):615-24.
Histone deacetylase inhibitors: a potential epigenetic treatment for Duchenne muscular dystrophy.
Authors:Consalvi S, Saccone V, Mozzetta C.
Source:Epigenomics. 2014;6(5):547-60. doi: 10.2217/epi.14.36
Pleiotropic antitumor effects of the pan-HDAC inhibitor ITF2357 against c-Myc-overexpressing human B-cell non-Hodgkin lymphomas.
Authors:Zappasodi R, Cavanè A, Iorio MV, Tortoreto M, Guarnotta C, Ruggiero G, Piovan C, Magni M, Zaffaroni N, Tagliabue E, Croce CM, Zunino F, Gianni AM, Di Nicola M.
Source:Int J Cancer. 2014 Nov 1;135(9):2034-45. doi: 10.1002/ijc.28852. Epub 2014 Mar 26.
BIM upregulation and ROS-dependent necroptosis mediate the antitumor effects of the HDACi Givinostat and Sorafenib in Hodgkin lymphoma cell line xenografts.
Authors:Locatelli SL, Cleris L, Stirparo GG, Tartari S, Saba E, Pierdominici M, Malorni W, Carbone A, Anichini A, Carlo-Stella C.
Source:Leukemia. 2014 Sep;28(9):1861-71. doi: 10.1038/leu.2014.81. Epub 2014 Feb 24.
The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F).
Authors:Guerini V, Barbui V, Spinelli O, Salvi A, Dellacasa C, Carobbio A, Introna M, Barbui T, Golay J, Rambaldi A.
Source:Leukemia. 2008 Apr;22(4):740-7. Epub 2007 Dec 13.
The HDAC inhibitor Givinostat modulates the hematopoietic transcription factors NFE2 and C-MYB in JAK2(V617F) myeloproliferative neoplasm cells.
Authors:Amaru Calzada A, Todoerti K, Donadoni L, Pellicioli A, Tuana G, Gatta R, Neri A, Finazzi G, Mantovani R, Rambaldi A, Introna M, Lombardi L, Golay J; AGIMM Investigators.
Source:Exp Hematol. 2012 Aug;40(8):634-45.e10. doi: 10.1016/j.exphem.2012.04.007. Epub 2012 May 8.
ITF2357 interferes with apoptosis and inflammatory pathways in the HL-60 model: a gene expression study.
Authors:Galimberti S, Canestraro M, Savli H, Palumbo GA, Tibullo D, Nagy B, Piaggi S, Guerrini F, Cine N, Metelli MR, Petrini M.
Source:Anticancer Res. 2010 Nov;30(11):4525-35.
Inhibition of HDAC activity by ITF2357 ameliorates joint inflammation and prevents cartilage and bone destruction in experimental arthritis.
Authors:Joosten LA, Leoni F, Meghji S, Mascagni P.
Source:Mol Med. 2011 May-Jun;17(5-6):391-6. doi: 10.2119/molmed.2011.00058. Epub 2011 Feb 11.
Histone deacetylase inhibitor ITF2357 is neuroprotective, improves functional recovery, and induces glial apoptosis following experimental traumatic brain injury.
Authors:Shein NA, Grigoriadis N, Alexandrovich AG, Simeonidou C, Lourbopoulos A, Polyzoidou E, Trembovler V, Mascagni P, Dinarello CA, Shohami E.
Source:FASEB J. 2009 Dec;23(12):4266-75. doi: 10.1096/fj.09-134700. Epub 2009 Sep 1.
Pleiotropic anti-myeloma activity of ITF2357: inhibition of interleukin-6 receptor signaling and repression of miR-19a and miR-19b.
Authors:Todoerti K, Barbui V, Pedrini O, Lionetti M, Fossati G, Mascagni P, Rambaldi A, Neri A, Introna M, Lombardi L, Golay J.
Source:Haematologica. 2010 Feb;95(2):260-9. doi: 10.3324/haematol.2009.012088. Epub 2009 Aug 27.
Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice.
Authors:Reddy P, Sun Y, Toubai T, Duran-Struuck R, Clouthier SG, Weisiger E, Maeda Y, Tawara I, Krijanovski O, Gatza E, Liu C, Malter C, Mascagni P, Dinarello CA, Ferrara JL.
Source:J Clin Invest. 2008 Jul;118(7):2562-73. doi: 10.1172/JCI34712.
The histone deacetylase inhibitor ITF2357 has anti-leukemic activity in vitro and in vivo and inhibits IL-6 and VEGF production by stromal cells.
Authors:Golay J, Cuppini L, Leoni F, Micò C, Barbui V, Domenghini M, Lombardi L, Neri A, Barbui AM, Salvi A, Pozzi P, Porro G, Pagani P, Fossati G, Mascagni P, Introna M, Rambaldi A.
Source:Leukemia. 2007 Sep;21(9):1892-900. Epub 2007 Jul 19.