Epigenetic Metalloenzymes

Christophe        Blanquart; Camille        Linot; Pierre-François        Cartron; Daniela        Tomaselli; Antonello        Mai; Philippe        Bertrand
doi:10.2174/0929867325666180706105903
Abstract

Epigenetics controls the expression of genes and is responsible for cellular phenotypes. The fundamental basis of these mechanisms involves in part the post-translational modifications (PTMs) of DNA and proteins, in particular, the nuclear histones. DNA can be methylated or demethylated on cytosine. Histones are marked by several modifications including acetylation and/or methylation, and of particular importance are the covalent modifications of lysine. There exists a balance between addition and removal of these PTMs, leading to three groups of enzymes involved in these processes: the writers adding marks, the erasers removing them, and the readers able to detect these marks and participating in the recruitment of transcription factors. The stimulation or the repression in the expression of genes is thus the result of a subtle equilibrium between all the possibilities coming from the combinations of these PTMs. Indeed, these mechanisms can be deregulated and then participate in the appearance, development and maintenance of various human diseases, including cancers, neurological and metabolic disorders. Some of the key players in epigenetics are metalloenzymes, belonging mostly to the group of erasers: the zinc-dependent histone deacetylases (HDACs), the iron-dependent lysine demethylases of the Jumonji family (JMJ or KDM) and for DNA the iron-dependent ten-eleven-translocation enzymes (TET) responsible for the oxidation of methylcytosine prior to the demethylation of DNA. This review presents these metalloenzymes, their importance in human disease and their inhibitors.
Keywords: DNMT, epigenetic, HDAC, TET, metalloenzymes, PTM.
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[1] 
Arrowsmith, C.H.; Bountra, C.; Fish, P.V.; Lee, K.; Schapira, M. Epigenetic protein families: a new frontier for drug discovery. Nat. Rev. Drug Discov.,  2012, 11(5), 384-400.
[http://dx.doi.org/10.1038/nrd3674] [PMID:  22498752] 
[2] 
Chang, B.; Chen, Y.; Zhao, Y.; Bruick, R.K. JMJD6 is a histone arginine demethylase. Science,  2007, 318(5849), 444-447.
[http://dx.doi.org/10.1126/science.1145801] [PMID:  17947579] 
[3] 
Frye, R.A. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem. Biophys. Res. Commun.,  2000, 273(2), 793-798.
[http://dx.doi.org/10.1006/bbrc.2000.3000] [PMID:  10873683] 
[4] 
Yang, X-J.; Grégoire, S.; Class, I.I. Class II histone deacetylases: from sequence to function, regulation, and clinical implication. Mol. Cell. Biol.,  2005, 25(8), 2873-2884.
[http://dx.doi.org/10.1128/MCB.25.8.2873-2884.2005] [PMID:  15798178] 
[5] 
Gaughan, L.; Logan, I.R.; Cook, S.; Neal, D.E.; Robson, C.N. Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor. J. Biol. Chem.,  2002, 277(29), 25904-25913.
[http://dx.doi.org/10.1074/jbc.M203423200] [PMID:  11994312] 
[6] 
Gu, W.; Roeder, R.G. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell,  1997, 90(4), 595-606.
[http://dx.doi.org/10.1016/S0092-8674(00)80521-8] [PMID:  9288740] 
[7] 
Jeong, J-W.; Bae, M-K.; Ahn, M-Y.; Kim, S-H.; Sohn, T-K.; Bae, M-H.; Yoo, M-A.; Song, E.J.; Lee, K-J.; Kim, K-W. Regulation and destabilization of HIF-1α by ARD1-mediated acetylation. Cell,  2002, 111(5), 709-720.
[http://dx.doi.org/10.1016/S0092-8674(02)01085-1] [PMID:  12464182] 
[8] 
Wang, C.; Fu, M.; Angeletti, R.H.; Siconolfi-Baez, L.; Reutens, A.T.; Albanese, C.; Lisanti, M.P.; Katzenellenbogen, B.S.; Kato, S.; Hopp, T.; Fuqua, S.A.W.; Lopez, G.N.; Kushner, P.J.; Pestell, R.G. Direct acetylation of the estrogen receptor α hinge region by p300 regulates transactivation and hormone sensitivity. J. Biol. Chem.,  2001, 276(21), 18375-18383.
[http://dx.doi.org/10.1074/jbc.M100800200] [PMID:  11279135] 
[9] 
Kovacs, J.J.; Murphy, P.J.M.; Gaillard, S.; Zhao, X.; Wu, J-T.; Nicchitta, C.V.; Yoshida, M.; Toft, D.O.; Pratt, W.B.; Yao, T-P. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol. Cell,  2005, 18(5), 601-607.
[http://dx.doi.org/10.1016/j.molcel.2005.04.021] [PMID:  15916966] 
[10] 
Yuan, Z.L.; Guan, Y.J.; Chatterjee, D.; Chin, Y.E. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science,  2005, 307(5707), 269-273.
[http://dx.doi.org/10.1126/science.1105166] [PMID:  15653507] 
[11] 
Hubbert, C.; Guardiola, A.; Shao, R.; Kawaguchi, Y.; Ito, A.; Nixon, A.; Yoshida, M.; Wang, X-F.; Yao, T-P. HDAC6 is a microtubule-associated deacetylase. Nature,  2002, 417(6887), 455-458.
[http://dx.doi.org/10.1038/417455a] [PMID:  12024216] 
[12] 
Morris, M.J.; Karra, A.S.; Monteggia, L.M. Histone deacetylases govern cellular mechanisms underlying behavioral and synaptic plasticity in the developing and adult brain. Behav. Pharmacol.,  2010, 21(5-6), 409-419.
[http://dx.doi.org/10.1097/FBP.0b013e32833c20c0] [PMID:  20555253] 
[13] 
Witt, O.; Deubzer, H.E.; Milde, T.; Oehme, I. HDAC family: What are the cancer relevant targets? Cancer Lett.,  2009, 277(1), 8-21.
[http://dx.doi.org/10.1016/j.canlet.2008.08.016] [PMID:  18824292] 
[14] 
Bhaskara, S.; Chyla, B.J.; Amann, J.M.; Knutson, S.K.; Cortez, D.; Sun, Z.W.; Hiebert, S.W. Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control. Mol. Cell,  2008, 30(1), 61-72.
[http://dx.doi.org/10.1016/j.molcel.2008.02.030] [PMID:  18406327] 
[15] 
Chang, S.; Young, B.D.; Li, S.; Qi, X.; Richardson, J.A.; Olson, E.N. Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Cell,  2006, 126(2), 321-334.
[http://dx.doi.org/10.1016/j.cell.2006.05.040] [PMID:  16873063] 
[16] 
Kasler, H.G.; Verdin, E. Histone deacetylase 7 functions as a key regulator of genes involved in both positive and negative selection of thymocytes. Mol. Cell. Biol.,  2007, 27(14), 5184-5200.
[http://dx.doi.org/10.1128/MCB.02091-06] [PMID:  17470548] 
[17] 
Pham, L.; Kaiser, B.; Romsa, A.; Schwarz, T.; Gopalakrishnan, R.; Jensen, E.D.; Mansky, K.C. HDAC3 and HDAC7 have opposite effects on osteoclast differentiation. J. Biol. Chem.,  2011, 286(14), 12056-12065.
[http://dx.doi.org/10.1074/jbc.M110.216853] [PMID:  21324898] 
[18] 
Fraga, M.F.; Ballestar, E.; Villar-Garea, A.; Boix-Chornet, M.; Espada, J.; Schotta, G.; Bonaldi, T.; Haydon, C.; Ropero, S.; Petrie, K.; Iyer, N.G.; Pérez-Rosado, A.; Calvo, E.; Lopez, J.A.; Cano, A.; Calasanz, M.J.; Colomer, D.; Piris, M.A.; Ahn, N.; Imhof, A.; Caldas, C.; Jenuwein, T.; Esteller, M. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat. Genet.,  2005, 37(4), 391-400.
[http://dx.doi.org/10.1038/ng1531] [PMID:  15765097] 
[19] 
Wilmott, J.S.; Colebatch, A.J.; Kakavand, H.; Shang, P.; Carlino, M.S.; Thompson, J.F.; Long, G.V.; Scolyer, R.A.; Hersey, P. Expression of the class 1 histone deacetylases HDAC8 and 3 are associated with improved survival of patients with metastatic melanoma. Mod. Pathol.,  2015, 28(7), 884-894.
[http://dx.doi.org/10.1038/modpathol.2015.34] [PMID:  25836739] 
[20] 
Parbin, S.; Kar, S.; Shilpi, A.; Sengupta, D.; Deb, M.; Rath, S.K.; Patra, S.K. Histone deacetylases: a saga of perturbed acetylation homeostasis in cancer. J. Histochem. Cytochem.,  2014, 62(1), 11-33.
[http://dx.doi.org/10.1369/0022155413506582] [PMID:  24051359] 
[21] 
Hahnen, E.; Hauke, J.; Tränkle, C.; Eyüpoglu, I.Y.; Wirth, B.; Blümcke, I. Histone deacetylase inhibitors: possible implications for neurodegenerative disorders. Expert Opin. Investig. Drugs,  2008, 17(2), 169-184.
[http://dx.doi.org/10.1517/13543784.17.2.169] [PMID:  18230051] 
[22] 
Lockett, G.A.; Wilkes, F.; Maleszka, R. Brain plasticity, memory and neurological disorders: an epigenetic perspective. Neuroreport,  2010, 21(14), 909-913.
[http://dx.doi.org/10.1097/WNR.0b013e32833e9288] [PMID:  20717061] 
[23] 
Vepsäläinen, S.; Helisalmi, S.; Mannermaa, A.; Pirttilä, T.; Soininen, H.; Hiltunen, M. Combined risk effects of IDE and NEP gene variants on Alzheimer disease. J. Neurol. Neurosurg. Psychiatry,  2009, 80(11), 1268-1270.
[http://dx.doi.org/10.1136/jnnp.2008.160002] [PMID:  19864659] 
[24] 
Hu, X-T.; Zhu, B-L.; Zhao, L-G.; Wang, J-W.; Liu, L.; Lai, Y-J.; He, L.; Deng, X-J.; Chen, G-J. Histone deacetylase inhibitor apicidin increases expression of the α-secretase ADAM10 through transcription factor USF1-mediated mechanisms. FASEB J.,  2017, 31(4), 1482-1493.
[http://dx.doi.org/10.1096/fj.201600961RR] [PMID:  28003340] 
[25] 
Qiu, X.; Xiao, X.; Li, N.; Li, Y. Histone deacetylases inhibitors (HDACis) as novel therapeutic application in various clinical diseases. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2017, 72, 60-72.
[http://dx.doi.org/10.1016/j.pnpbp.2016.09.002] [PMID:  27614213] 
[26] 
Cook, C.; Carlomagno, Y.; Gendron, T.F.; Dunmore, J.; Scheffel, K.; Stetler, C.; Davis, M.; Dickson, D.; Jarpe, M.; DeTure, M.; Petrucelli, L. Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Hum. Mol. Genet.,  2014, 23(1), 104-116.
[http://dx.doi.org/10.1093/hmg/ddt402] [PMID:  23962722] 
[27] 
Zhu, X.; Wang, S.; Yu, L.; Jin, J.; Ye, X.; Liu, Y.; Xu, Y. HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer’s disease. Aging Cell,  2017, 16(5), 1073-1082.
[http://dx.doi.org/10.1111/acel.12642] [PMID:  28771976] 
[28] 
Kee, H.J.; Kook, H. Roles and targets of class I and IIa histone deacetylases in cardiac hypertrophy. J. Biomed. Biotechnol.,  2011, 2011928326
[http://dx.doi.org/10.1155/2011/928326] [PMID:  21151616] 
[29] 
Lee, T-I.; Kao, Y-H.; Tsai, W-C.; Chung, C-C.; Chen, Y-C.; Chen, Y-J. HDAC inhibition modulates cardiac ppars and fatty acid metabolism in diabetic cardiomyopathy. PPAR Res.,  2016, 20165938740
[http://dx.doi.org/10.1155/2016/5938740] [PMID:  27446205] 
[30] 
Chen, Y.; Du, J.; Zhao, Y.T.; Zhang, L.; Lv, G.; Zhuang, S.; Qin, G.; Zhao, T.C. Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice. Cardiovasc. Diabetol.,  2015, 14, 99-99.
[http://dx.doi.org/10.1186/s12933-015-0262-8] [PMID:  26245924] 
[31] 
Cardinale, J.P.; Sriramula, S.; Pariaut, R.; Guggilam, A.; Mariappan, N.; Elks, C.M.; Francis, J. HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats. Hypertension,  2010, 56(3), 437-444.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.154567] [PMID:  20679181] 
[32] 
Kao, Y-H.; Liou, J-P.; Chung, C-C.; Lien, G-S.; Kuo, C-C.; Chen, S-A.; Chen, Y-J. Histone deacetylase inhibition improved cardiac functions with direct antifibrotic activity in heart failure. Int. J. Cardiol.,  2013, 168, 4178-4183.
[http://dx.doi.org/10.1016/j.ijcard.2013.07.111] [PMID:  23931972] 
[33] 
Zhang, L.; Chen, B.; Zhao, Y.; Dubielecka, P.M.; Wei, L.; Qin, G.J.; Chin, Y.E.; Wang, Y.; Zhao, T.C. Inhibition of histone deacetylase-induced myocardial repair is mediated by c-kit in infarcted hearts. J. Biol. Chem.,  2012, 287(47), 39338-39348.
[http://dx.doi.org/10.1074/jbc.M112.379115] [PMID:  23024362] 
[34] 
Tao, H.; Shi, K-H.; Yang, J-J.; Huang, C.; Zhan, H-Y.; Li, J. Histone deacetylases in cardiac fibrosis: current perspectives for therapy. Cell. Signal.,  2014, 26(3), 521-527.
[http://dx.doi.org/10.1016/j.cellsig.2013.11.037] [PMID:  24321371] 
[35] 
Zampetaki, A.; Zeng, L.; Margariti, A.; Xiao, Q.; Li, H.; Zhang, Z.; Pepe, A.E.; Wang, G.; Habi, O.; deFalco, E.; Cockerill, G.; Mason, J.C.; Hu, Y.; Xu, Q. Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow. Circulation,  2010, 121(1), 132-142.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.890491] [PMID:  20026773] 
[36] 
Licciardi, P.V.; Ververis, K.; Tang, M.L.; El-Osta, A.; Karagiannis, T.C. Immunomodulatory effects of histone deacetylase inhibitors. Curr. Mol. Med.,  2013, 13(4), 640-647.
[http://dx.doi.org/10.2174/1566524011313040013] [PMID:  23061676] 
[37] 
Buckland, J. Rheumatoid arthritis: HDAC and HDACi: pathogenetic and mechanistic insights. Nat. Rev. Rheumatol.,  2011, 7(12), 682.
[http://dx.doi.org/10.1038/nrrheum.2011.162] [PMID:  22009328] 
[38] 
Saouaf, S.J.; Li, B.; Zhang, G.; Shen, Y.; Furuuchi, N.; Hancock, W.W.; Greene, M.I. Deacetylase inhibition increases regulatory T cell function and decreases incidence and severity of collagen-induced arthritis. Exp. Mol. Pathol.,  2009, 87(2), 99-104.
[http://dx.doi.org/10.1016/j.yexmp.2009.06.003] [PMID:  19577564] 
[39] 
Choo, Q-Y.; Ho, P.C.; Tanaka, Y.; Lin, H-S. Histone deacetylase inhibitors MS-275 and SAHA induced growth arrest and suppressed lipopolysaccharide-stimulated NF-kappaB p65 nuclear accumulation in human rheumatoid arthritis synovial fibroblastic E11 cells. Rheumatology (Oxford),  2010, 49(8), 1447-1460.
[http://dx.doi.org/10.1093/rheumatology/keq108] [PMID:  20421217] 
[40] 
Vojinovic, J.; Damjanov, N. HDAC inhibition in rheumatoid arthritis and juvenile idiopathic arthritis. Mol. Med.,  2011, 17(5-6), 397-403.
[http://dx.doi.org/10.2119/molmed.2011.00030] [PMID:  21308151] 
[41] 
Oh, B.R.; Suh, D.H.; Bae, D.; Ha, N.; Choi, Y.I.; Yoo, H.J.; Park, J.K.; Lee, E.Y.; Lee, E.B.; Song, Y.W. Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitro. Arthritis Res. Ther.,  2017, 19(1), 154.
[http://dx.doi.org/10.1186/s13075-017-1357-2] [PMID:  28673326] 
[42] 
Angiolilli, C.; Kabala, P.A.; Grabiec, A.M.; Van Baarsen, I.M.; Ferguson, B.S.; García, S.; Malvar Fernandez, B.; McKinsey, T.A.; Tak, P.P.; Fossati, G.; Mascagni, P.; Baeten, D.L.; Reedquist, K.A. Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes. Ann. Rheum. Dis.,  2017, 76(1), 277-285.
[http://dx.doi.org/10.1136/annrheumdis-2015-209064] [PMID:  27457515] 
[43] 
Chomont, N.; El-Far, M.; Ancuta, P.; Trautmann, L.; Procopio, F.A.; Yassine-Diab, B.; Boucher, G.; Boulassel, M-R.; Ghattas, G.; Brenchley, J.M.; Schacker, T.W.; Hill, B.J.; Douek, D.C.; Routy, J-P.; Haddad, E.K.; Sékaly, R-P. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med.,  2009, 15(8), 893-900.
[http://dx.doi.org/10.1038/nm.1972] [PMID:  19543283] 
[44] 
Archin, N.M.; Espeseth, A.; Parker, D.; Cheema, M.; Hazuda, D.; Margolis, D.M. Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid. AIDS Res. Hum. Retroviruses,  2009, 25(2), 207-212.
[http://dx.doi.org/10.1089/aid.2008.0191] [PMID:  19239360] 
[45] 
Coull, J.J.; Romerio, F.; Sun, J-M.; Volker, J.L.; Galvin, K.M.; Davie, J.R.; Shi, Y.; Hansen, U.; Margolis, D.M. The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1. J. Virol.,  2000, 74(15), 6790-6799.
[http://dx.doi.org/10.1128/JVI.74.15.6790-6799.2000] [PMID:  10888618] 
[46] 
McManamy, M.E.M.; Hakre, S.; Verdin, E.M.; Margolis, D.M. Therapy for latent human immunodeficiency virus type 1 infection: the role of histone deacetylase inhibitors. Antivir. Chem. Chemother.,  2014, 23, 145-149.
[http://dx.doi.org/10.3851/IMP2551] [PMID:  24318952] 
[47] 
Archin, N.M.; Keedy, K.S.; Espeseth, A.; Dang, H.; Hazuda, D.J.; Margolis, D.M. Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS,  2009, 23(14), 1799-1806.
[http://dx.doi.org/10.1097/QAD.0b013e32832ec1dc] [PMID:  19590405] 
[48] 
Huber, K.; Doyon, G.; Plaks, J.; Fyne, E.; Mellors, J.W.; Sluis-Cremer, N. Inhibitors of histone deacetylases: correlation between isoform specificity and reactivation of HIV type 1 (HIV-1) from latently infected cells. J. Biol. Chem.,  2011, 286(25), 22211-22218.
[http://dx.doi.org/10.1074/jbc.M110.180224] [PMID:  21531716] 
[49] 
Archin, N.M.; Liberty, A.L.; Kashuba, A.D.; Choudhary, S.K.; Kuruc, J.D.; Crooks, A.M.; Parker, D.C.; Anderson, E.M.; Kearney, M.F.; Strain, M.C.; Richman, D.D.; Hudgens, M.G.; Bosch, R.J.; Coffin, J.M.; Eron, J.J.; Hazuda, D.J.; Margolis, D.M. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature,  2012, 487(7408), 482-485.
[http://dx.doi.org/10.1038/nature11286] [PMID:  22837004] 
[50] 
Lehrman, G.; Hogue, I.B.; Palmer, S.; Jennings, C.; Spina, C.A.; Wiegand, A.; Landay, A.L.; Coombs, R.W.; Richman, D.D.; Mellors, J.W.; Coffin, J.M.; Bosch, R.J.; Margolis, D.M. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet,  2005, 366(9485), 549-555.
[http://dx.doi.org/10.1016/S0140-6736(05)67098-5] [PMID:  16099290] 
[51] 
Wei, D.G.; Chiang, V.; Fyne, E.; Balakrishnan, M.; Barnes, T.; Graupe, M.; Hesselgesser, J.; Irrinki, A.; Murry, J.P.; Stepan, G.; Stray, K.M.; Tsai, A.; Yu, H.; Spindler, J.; Kearney, M.; Spina, C.A.; McMahon, D.; Lalezari, J.; Sloan, D.; Mellors, J.; Geleziunas, R.; Cihlar, T. Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing. PLoS Pathog.,  2014, 10(4)e1004071
[http://dx.doi.org/10.1371/journal.ppat.1004071] [PMID:  24722454] 
[52] 
Roche, J.; Bertrand, P. Inside HDACs with more selective HDAC inhibitors. Eur. J. Med. Chem.,  2016, 121, 451-483.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.047] [PMID:  27318122] 
[53] 
Bertrand, P. Inside HDAC with HDAC inhibitors. Eur. J. Med. Chem.,  2010, 45(6), 2095-2116.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.030] [PMID:  20223566] 
[54] 
Marks, P.A. Discovery and development of SAHA as an anticancer agent. Oncogene,  2007, 26(9), 1351-1356.
[http://dx.doi.org/10.1038/sj.onc.1210204] [PMID:  17322921] 
[55] 
Poole, R.M. Belinostat: first global approval. Drugs,  2014, 74(13), 1543-1554.
[http://dx.doi.org/10.1007/s40265-014-0275-8] [PMID:  25134672] 
[56] 
Richardson, P.G.; Laubach, J.P.; Lonial, S.; Moreau, P.; Yoon, S-S.; Hungria, V.T.; Dimopoulos, M.A.; Beksac, M.; Alsina, M.; San-Miguel, J.F. Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma. Expert Rev. Anticancer Ther.,  2015, 15(7), 737-748.
[http://dx.doi.org/10.1586/14737140.2015.1047770] [PMID:  26051506] 
[57] 
Tamara Vanhaecke, Peggy Papeleu, Greetje Elaut and Vera Rogiers, Trichostatin A - like Hydroxamate Histone Deacetylase Inhibitors as Therapeutic Agents: Toxicological Point of View. Curr. Med. Chem.,  2004, 11, 1629-1643.
[http://dx.doi.org/10.2174/0929867043365099] 
[58] 
Mottamal, M.; Zheng, S.; Huang, T.L.; Wang, G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules,  2015, 3898-4183.
[59] 
Grant, C.; Rahman, F.; Piekarz, R.; Peer, C.; Frye, R.; Robey, R.W.; Gardner, E.R.; Figg, W.D.; Bates, S.E. Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors. Expert Rev. Anticancer Ther.,  2010, 10(7), 997-1008.
[http://dx.doi.org/10.1586/era.10.88] [PMID:  20645688] 
[60] 
Kelly, W.K.; O’Connor, O.A.; Krug, L.M.; Chiao, J.H.; Heaney, M.; Curley, T.; MacGregore-Cortelli, B.; Tong, W.; Secrist, J.P.; Schwartz, L.; Richardson, S.; Chu, E.; Olgac, S.; Marks, P.A.; Scher, H.; Richon, V.M. Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J. Clin. Oncol.,  2005, 23(17), 3923-3931.
[http://dx.doi.org/10.1200/JCO.2005.14.167] [PMID:  15897550] 
[61] 
Rubin, E.H.; Agrawal, N.G.; Friedman, E.J.; Scott, P.; Mazina, K.E.; Sun, L.; Du, L.; Ricker, J.L.; Frankel, S.R.; Gottesdiener, K.M.; Wagner, J.A.; Iwamoto, M. A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer. Clin. Cancer Res.,  2006, 12(23), 7039-7045.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1802] [PMID:  17145826] 
[62] 
Mann, B.S.; Johnson, J.R.; Cohen, M.H.; Justice, R.; Pazdur, R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist,  2007, 12(10), 1247-1252.
[http://dx.doi.org/10.1634/theoncologist.12-10-1247] [PMID:  17962618] 
[63] 
Krug, L.M.; Kindler, H.L.; Calvert, H.; Manegold, C.; Tsao, A.S.; Fennell, D.; Öhman, R.; Plummer, R.; Eberhardt, W.E.; Fukuoka, K.; Gaafar, R.M.; Lafitte, J.J.; Hillerdal, G.; Chu, Q.; Buikhuisen, W.A.; Lubiniecki, G.M.; Sun, X.; Smith, M.; Baas, P. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol.,  2015, 16(4), 447-456.
[http://dx.doi.org/10.1016/S1470-2045(15)70056-2] [PMID:  25800891] 
[64] 
Nakajima, H.; Kim, Y.B.; Terano, H.; Yoshida, M.; Horinouchi, S. FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor. Exp. Cell Res.,  1998, 241(1), 126-133.
[http://dx.doi.org/10.1006/excr.1998.4027] [PMID:  9633520] 
[65] 
Sandor, V.; Bakke, S.; Robey, R.W.; Kang, M.H.; Blagosklonny, M.V.; Bender, J.; Brooks, R.; Piekarz, R.L.; Tucker, E.; Figg, W.D.; Chan, K.K.; Goldspiel, B.; Fojo, A.T.; Balcerzak, S.P.; Bates, S.E. Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms. Clin. Cancer Res.,  2002, 8(3), 718-728.
[PMID:  11895901] 
[66] 
Schrump, D.S.; Fischette, M.R.; Nguyen, D.M.; Zhao, M.; Li, X.; Kunst, T.F.; Hancox, A.; Hong, J.A.; Chen, G.A.; Kruchin, E.; Wright, J.J.; Rosing, D.R.; Sparreboom, A.; Figg, W.D.; Steinberg, S.M. Clinical and molecular responses in lung cancer patients receiving Romidepsin. Clin. Cancer Res.,  2008, 14(1), 188-198.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-0135] [PMID:  18172270] 
[67] 
Piekarz, R.L.; Frye, R.; Turner, M.; Wright, J.J.; Allen, S.L.; Kirschbaum, M.H.; Zain, J.; Prince, H.M.; Leonard, J.P.; Geskin, L.J.; Reeder, C.; Joske, D.; Figg, W.D.; Gardner, E.R.; Steinberg, S.M.; Jaffe, E.S.; Stetler-Stevenson, M.; Lade, S.; Fojo, A.T.; Bates, S.E. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J. Clin. Oncol.,  2009, 27(32), 5410-5417.
[http://dx.doi.org/10.1200/JCO.2008.21.6150] [PMID:  19826128] 
[68] 
Coiffier, B.; Pro, B.; Prince, H.M.; Foss, F.; Sokol, L.; Greenwood, M.; Caballero, D.; Borchmann, P.; Morschhauser, F.; Wilhelm, M.; Pinter-Brown, L.; Padmanabhan, S.; Shustov, A.; Nichols, J.; Carroll, S.; Balser, J.; Balser, B.; Horwitz, S. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J. Clin. Oncol.,  2012, 30(6), 631-636.
[http://dx.doi.org/10.1200/JCO.2011.37.4223] [PMID:  22271479] 
[69] 
Grant, C.; Rahman, F.; Piekarz, R.; Peer, C.; Frye, R.; Robey, R.W.; Gardner, E.R.; Figg, W.D.; Bates, S.E. Romidepsin: a new therapy for cutaneous T-cell lymphoma and a potential therapy for solid tumors. Expert Rev. Anticancer Ther.,  2010, 10(7), 997-1008.
[http://dx.doi.org/10.1586/era.10.88] [PMID:  20645688] 
[70] 
Lassen, U.; Molife, L.R.; Sorensen, M.; Engelholm, S.A.; Vidal, L.; Sinha, R.; Penson, R.T.; Buhl-Jensen, P.; Crowley, E.; Tjornelund, J.; Knoblauch, P.; de Bono, J.S. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours. Br. J. Cancer,  2010, 103(1), 12-17.
[http://dx.doi.org/10.1038/sj.bjc.6605726] [PMID:  20588278] 
[71] 
Steele, N.L.; Plumb, J.A.; Vidal, L.; Tjørnelund, J.; Knoblauch, P.; Buhl-Jensen, P.; Molife, R.; Brown, R.; de Bono, J.S.; Evans, T.R. Pharmacokinetic and pharmacodynamic properties of an oral formulation of the histone deacetylase inhibitor Belinostat (PXD101). Cancer Chemother. Pharmacol.,  2011, 67(6), 1273-1279.
[http://dx.doi.org/10.1007/s00280-010-1419-5] [PMID:  20706839] 
[72] 
Yeo, W.; Chung, H.C.; Chan, S.L.; Wang, L.Z.; Lim, R.; Picus, J.; Boyer, M.; Mo, F.K.; Koh, J.; Rha, S.Y.; Hui, E.P.; Jeung, H.C.; Roh, J.K.; Yu, S.C.; To, K.F.; Tao, Q.; Ma, B.B.; Chan, A.W.; Tong, J.H.; Erlichman, C.; Chan, A.T.; Goh, B.C. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group. J. Clin. Oncol.,  2012, 30(27), 3361-3367.
[http://dx.doi.org/10.1200/JCO.2011.41.2395] [PMID:  22915658] 
[73] 
O’Connor, O.A.; Horwitz, S.; Masszi, T.; Van Hoof, A.; Brown, P.; Doorduijn, J.; Hess, G.; Jurczak, W.; Knoblauch, P.; Chawla, S.; Bhat, G.; Choi, M.R.; Walewski, J.; Savage, K.; Foss, F.; Allen, L.F.; Shustov, A. belinostat in patients with relapsed or refractory peripheral T-Cell lymphoma: results of the Pivotal Phase II BELIEF (CLN-19) Study. J. Clin. Oncol.,  2015, 33(23), 2492-2499.
[http://dx.doi.org/10.1200/JCO.2014.59.2782] [PMID:  26101246] 
[74] 
Foss, F.; Advani, R.; Duvic, M.; Hymes, K.B.; Intragumtornchai, T.; Lekhakula, A.; Shpilberg, O.; Lerner, A.; Belt, R.J.; Jacobsen, E.D.; Laurent, G.; Ben-Yehuda, D.; Beylot-Barry, M.; Hillen, U.; Knoblauch, P.; Bhat, G.; Chawla, S.; Allen, L.F.; Pohlman, B. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br. J. Haematol.,  2015, 168(6), 811-819.
[http://dx.doi.org/10.1111/bjh.13222] [PMID:  25404094] 
[75] 
Steele, N.L.; Plumb, J.A.; Vidal, L.; Tjørnelund, J.; Knoblauch, P.; Rasmussen, A.; Ooi, C.E.; Buhl-Jensen, P.; Brown, R.; Evans, T.R.; DeBono, J.S. A phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor belinostat in patients with advanced solid tumors. Clin. Cancer Res.,  2008, 14(3), 804-810.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1786] [PMID:  18245542] 
[76] 
Ramalingam, S.S.; Belani, C.P.; Ruel, C.; Frankel, P.; Gitlitz, B.; Koczywas, M.; Espinoza-Delgado, I.; Gandara, D. Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma. J. Thorac. Oncol.,  2009, 4(1), 97-101.
[http://dx.doi.org/10.1097/JTO.0b013e318191520c] [PMID:  19096314] 
[77] 
Giles, F.; Fischer, T.; Cortes, J.; Garcia-Manero, G.; Beck, J.; Ravandi, F.; Masson, E.; Rae, P.; Laird, G.; Sharma, S.; Kantarjian, H.; Dugan, M.; Albitar, M.; Bhalla, K. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin. Cancer Res.,  2006, 12(15), 4628-4635.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-0511] [PMID:  16899611] 
[78] 
Morita, S.; Oizumi, S.; Minami, H.; Kitagawa, K.; Komatsu, Y.; Fujiwara, Y.; Inada, M.; Yuki, S.; Kiyota, N.; Mitsuma, A.; Sawaki, M.; Tanii, H.; Kimura, J.; Ando, Y. Phase I dose-escalating study of panobinostat (LBH589) administered intravenously to Japanese patients with advanced solid tumors. Invest. New Drugs,  2012, 30(5), 1950-1957.
[http://dx.doi.org/10.1007/s10637-011-9751-0] [PMID:  21964801] 
[79] 
Sharma, S.; Witteveen, P.O.; Lolkema, M.P.; Hess, D.; Gelderblom, H.; Hussain, S.A.; Porro, M.G.; Waldron, E.; Valera, S.Z.; Mu, S. A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of renal function. Cancer Chemother. Pharmacol.,  2015, 75(1), 87-95.
[http://dx.doi.org/10.1007/s00280-014-2612-8] [PMID:  25377157] 
[80] 
Younes, A.; Sureda, A.; Ben-Yehuda, D.; Zinzani, P.L.; Ong, T.C.; Prince, H.M.; Harrison, S.J.; Kirschbaum, M.; Johnston, P.; Gallagher, J.; Le Corre, C.; Shen, A.; Engert, A. Panobinostat in patients with relapsed/refractory Hodgkin’s lymphoma after autologous stem-cell transplantation: results of a phase II study. J. Clin. Oncol.,  2012, 30(18), 2197-2203.
[http://dx.doi.org/10.1200/JCO.2011.38.1350] [PMID:  22547596] 
[81] 
San-Miguel, J.F.; Hungria, V.T.; Yoon, S.S.; Beksac, M.; Dimopoulos, M.A.; Elghandour, A.; Jedrzejczak, W.W.; Günther, A.; Nakorn, T.N.; Siritanaratkul, N.; Corradini, P.; Chuncharunee, S.; Lee, J.J.; Schlossman, R.L.; Shelekhova, T.; Yong, K.; Tan, D.; Numbenjapon, T.; Cavenagh, J.D.; Hou, J.; LeBlanc, R.; Nahi, H.; Qiu, L.; Salwender, H.; Pulini, S.; Moreau, P.; Warzocha, K.; White, D.; Bladé, J.; Chen, W.; de la Rubia, J.; Gimsing, P.; Lonial, S.; Kaufman, J.L.; Ocio, E.M.; Veskovski, L.; Sohn, S.K.; Wang, M.C.; Lee, J.H.; Einsele, H.; Sopala, M.; Corrado, C.; Bengoudifa, B.R.; Binlich, F.; Richardson, P.G. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol.,  2014, 15(11), 1195-1206.
[http://dx.doi.org/10.1016/S1470-2045(14)70440-1] [PMID:  25242045] 
[82] 
Qiao, Z.; Ren, S.; Li, W.; Wang, X.; He, M.; Guo, Y.; Sun, L.; He, Y.; Ge, Y.; Yu, Q. Chidamide, a novel histone deacetylase inhibitor, synergistically enhances gemcitabine cytotoxicity in pancreatic cancer cells. Biochem. Biophys. Res. Commun.,  2013, 434(1), 95-101.
[http://dx.doi.org/10.1016/j.bbrc.2013.03.059] [PMID:  23541946] 
[83] 
Saito, A.; Yamashita, T.; Mariko, Y.; Nosaka, Y.; Tsuchiya, K.; Ando, T.; Suzuki, T.; Tsuruo, T.; Nakanishi, O. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc. Natl. Acad. Sci. USA,  1999, 96(8), 4592-4597.
[http://dx.doi.org/10.1073/pnas.96.8.4592] [PMID:  10200307] 
[84] 
Ryan, Q.C.; Headlee, D.; Acharya, M.; Sparreboom, A.; Trepel, J.B.; Ye, J.; Figg, W.D.; Hwang, K.; Chung, E.J.; Murgo, A.; Melillo, G.; Elsayed, Y.; Monga, M.; Kalnitskiy, M.; Zwiebel, J.; Sausville, E.A. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J. Clin. Oncol.,  2005, 23(17), 3912-3922.
[http://dx.doi.org/10.1200/JCO.2005.02.188] [PMID:  15851766] 
[85] 
Batlevi, C.L.; Kasamon, Y.; Bociek, R.G.; Lee, P.; Gore, L.; Copeland, A.; Sorensen, R.; Ordentlich, P.; Cruickshank, S.; Kunkel, L.; Buglio, D.; Hernandez-Ilizaliturri, F.; Younes, A. ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma. Haematologica,  2016, 101(8), 968-975.
[http://dx.doi.org/10.3324/haematol.2016.142406] [PMID:  27151994] 
[86] 
Lobera, M.; Madauss, K.P.; Pohlhaus, D.T.; Wright, Q.G.; Trocha, M.; Schmidt, D.R.; Baloglu, E.; Trump, R.P.; Head, M.S.; Hofmann, G.A.; Murray-Thompson, M.; Schwartz, B.; Chakravorty, S.; Wu, Z.; Mander, P.K.; Kruidenier, L.; Reid, R.A.; Burkhart, W.; Turunen, B.J.; Rong, J.X.; Wagner, C.; Moyer, M.B.; Wells, C.; Hong, X.; Moore, J.T.; Williams, J.D.; Soler, D.; Ghosh, S.; Nolan, M.A. Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat. Chem. Biol.,  2013, 9(5), 319-325.
[http://dx.doi.org/10.1038/nchembio.1223] [PMID:  23524983] 
[87] 
Evens, A.M.; Balasubramanian, S.; Vose, J.M.; Harb, W.; Gordon, L.I.; Langdon, R.; Sprague, J.; Sirisawad, M.; Mani, C.; Yue, J.; Luan, Y.; Horton, S.; Graef, T.; Bartlett, N.L. A Phase I/II Multicenter, open-label study of the oral histone deacetylase inhibitor abexinostat in relapsed/refractory lymphoma. Clin. Cancer Res.,  2016, 22(5), 1059-1066.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0624] [PMID:  26482040] 
[88] 
Rivera-Del Valle, N.; Gao, S.; Miller, C.P.; Fulbright, J.; Gonzales, C.; Sirisawad, M.; Steggerda, S.; Wheler, J.; Balasubramanian, S.; Chandra, J. A Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells. Int. J. Cell Biol.,  2010, 2010207420
[89] 
Buggy, J.J.; Cao, Z.A.; Bass, K.E.; Verner, E.; Balasubramanian, S.; Liu, L.; Schultz, B.E.; Young, P.R.; Dalrymple, S.A. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol. Cancer Ther.,  2006, 5(5), 1309-1317.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0442] [PMID:  16731764] 
[90] 
Novotny-Diermayr, V.; Sangthongpitag, K.; Hu, C.Y.; Wu, X.; Sausgruber, N.; Yeo, P.; Greicius, G.; Pettersson, S.; Liang, A.L.; Loh, Y.K.; Bonday, Z.; Goh, K.C.; Hentze, H.; Hart, S.; Wang, H.; Ethirajulu, K.; Wood, J.M. SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol. Cancer Ther.,  2010, 9(3), 642-652.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0689] [PMID:  20197387] 
[91] 
Novotny-Diermayr, V.; Sausgruber, N.; Loh, Y.K.; Pasha, M.K.; Jayaraman, R.; Hentze, H.; Yong, W-P.; Goh, B-C.; Toh, H-C.; Ethirajulu, K.; Zhu, J.; Wood, J.M. Pharmacodynamic evaluation of the target efficacy of SB939, an oral HDAC inhibitor with selectivity for tumor tissue. Mol. Cancer Ther.,  2011, 10(7), 1207-1217.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0044] [PMID:  21586629] 
[92] 
Tong, W-G.; Wei, Y.; Stevenson, W.; Kuang, S-Q.; Fang, Z.; Zhang, M.; Arts, J.; Garcia-Manero, G. Preclinical antileukemia activity of JNJ-26481585, a potent second-generation histone deacetylase inhibitor. Leuk. Res.,  2010, 34(2), 221-228.
[http://dx.doi.org/10.1016/j.leukres.2009.07.024] [PMID:  19682743] 
[93] 
Child, F.; Ortiz-Romero, P.L.; Alvarez, R.; Bagot, M.; Stadler, R.; Weichenthal, M.; Alves, R.; Quaglino, P.; Beylot-Barry, M.; Cowan, R.; Geskin, L.J.; Pérez-Ferriols, A.; Hellemans, P.; Elsayed, Y.; Phelps, C.; Forslund, A.; Kamida, M.; Zinzani, P.L. Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sézary syndrome. Br. J. Dermatol.,  2016, 175(1), 80-88.
[http://dx.doi.org/10.1111/bjd.14427] [PMID:  26836950] 
[94] 
Bao, L.; Diao, H.; Dong, N.; Su, X.; Wang, B.; Mo, Q.; Yu, H.; Wang, X.; Chen, C. Histone deacetylase inhibitor induces cell apoptosis and cycle arrest in lung cancer cells via mitochondrial injury and p53 up-acetylation. Cell Biol. Toxicol.,  2016, 32(6), 469-482.
[http://dx.doi.org/10.1007/s10565-016-9347-8] [PMID:  27423454] 
[95] 
Arts, J.; King, P.; Mariën, A.; Floren, W.; Beliën, A.; Janssen, L.; Pilatte, I.; Roux, B.; Decrane, L.; Gilissen, R.; Hickson, I.; Vreys, V.; Cox, E.; Bol, K.; Talloen, W.; Goris, I.; Andries, L.; Du Jardin, M.; Janicot, M.; Page, M.; van Emelen, K.; Angibaud, P. JNJ-26481585, a novel “second-generation” oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin. Cancer Res.,  2009, 15(22), 6841-6851.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0547] [PMID:  19861438] 
[96] 
Yee, A.J.; Bensinger, W.I.; Supko, J.G.; Voorhees, P.M.; Berdeja, J.G.; Richardson, P.G.; Libby, E.N.; Wallace, E.E.; Birrer, N.E.; Burke, J.N.; Tamang, D.L.; Yang, M.; Jones, S.S.; Wheeler, C.A.; Markelewicz, R.J.; Raje, N.S. Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial. Lancet Oncol.,  2016, 17(11), 1569-1578.
[http://dx.doi.org/10.1016/S1470-2045(16)30375-8] [PMID:  27646843] 
[97] 
Santo, L.; Hideshima, T.; Kung, A.L.; Tseng, J-C.; Tamang, D.; Yang, M.; Jarpe, M.; van Duzer, J.H.; Mazitschek, R.; Ogier, W.C.; Cirstea, D.; Rodig, S.; Eda, H.; Scullen, T.; Canavese, M.; Bradner, J.; Anderson, K.C.; Jones, S.S.; Raje, N. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood,  2012, 119(11), 2579-2589.
[http://dx.doi.org/10.1182/blood-2011-10-387365] [PMID:  22262760] 
[98] 
Nawrocki, S.T.; Carew, J.S.; Maclean, K.H.; Courage, J.F.; Huang, P.; Houghton, J.A.; Cleveland, J.L.; Giles, F.J.; McConkey, D.J. Myc regulates aggresome formation, the induction of Noxa, and apoptosis in response to the combination of bortezomib and SAHA. Blood,  2008, 112(7), 2917-2926.
[http://dx.doi.org/10.1182/blood-2007-12-130823] [PMID:  18641367] 
[99] 
Naymagon, L.; Abdul-Hay, M. Novel agents in the treatment of multiple myeloma: a review about the future. J. Hematol. Oncol.,  2016, 9(1), 52.
[http://dx.doi.org/10.1186/s13045-016-0282-1] [PMID:  27363832] 
[100] 
Chhabra, S. Novel Proteasome Inhibitors and Histone Deacetylase Inhibitors: Progress in Myeloma Therapeutics. Pharmaceuticals (Basel),  2017, 10(2)E40
[http://dx.doi.org/10.3390/ph10020040] [PMID:  28398261] 
[101] 
Lin, E.Y.; Jones, J.G.; Li, P.; Zhu, L.; Whitney, K.D.; Muller, W.J.; Pollard, J.W. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am. J. Pathol.,  2003, 163(5), 2113-2126.
[http://dx.doi.org/10.1016/S0002-9440(10)63568-7] [PMID:  14578209] 
[102] 
Guerriero, J.L.; Sotayo, A.; Ponichtera, H.E.; Castrillon, J.A.; Pourzia, A.L.; Schad, S.; Johnson, S.F.; Carrasco, R.D.; Lazo, S.; Bronson, R.T.; Davis, S.P.; Lobera, M.; Nolan, M.A.; Letai, A. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature,  2017, 543(7645), 428-432.
[http://dx.doi.org/10.1038/nature21409] [PMID:  28273064] 
[103] 
Huang, P.; Almeciga-Pinto, I.; Jarpe, M.; van Duzer, J.H.; Mazitschek, R.; Yang, M.; Jones, S.S.; Quayle, S.N. Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models. Oncotarget,  2017, 8(2), 2694-2707.
[http://dx.doi.org/10.18632/oncotarget.13738] [PMID:  27926524] 
[104] 
Eickhoff, B.; Rüller, S.; Laue, T.; Köhler, G.; Stahl, C.; Schlaak, M.; van der Bosch, J. Trichostatin A modulates expression of p21waf1/cip1, Bcl-xL, ID1, ID2, ID3, CRAB2, GATA-2, hsp86 and TFIID/TAFII31 mRNA in human lung adenocarcinoma cells. Biol. Chem.,  2000, 381(2), 107-112.
[http://dx.doi.org/10.1515/BC.2000.015] [PMID:  10746741] 
[105] 
Shin, J.Y.; Kim, H.S.; Park, J.; Park, J.B.; Lee, J.Y. Mechanism for inactivation of the KIP family cyclin-dependent kinase inhibitor genes in gastric cancer cells. Cancer Res.,  2000, 60(2), 262-265.
[PMID:  10667572] 
[106] 
Vrana, J.A.; Decker, R.H.; Johnson, C.R.; Wang, Z.; Jarvis, W.D.; Richon, V.M.; Ehinger, M.; Fisher, P.B.; Grant, S. Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53. Oncogene,  1999, 18(50), 7016-7025.
[http://dx.doi.org/10.1038/sj.onc.1203176] [PMID:  10597302] 
[107] 
Archer, S.Y.; Meng, S.; Shei, A.; Hodin, R.A. p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells. Proc. Natl. Acad. Sci. USA,  1998, 95(12), 6791-6796.
[http://dx.doi.org/10.1073/pnas.95.12.6791] [PMID:  9618491] 
[108] 
el-Deiry, W.S.; Tokino, T.; Velculescu, V.E.; Levy, D.B.; Parsons, R.; Trent, J.M.; Lin, D.; Mercer, W.E.; Kinzler, K.W.; Vogelstein, B. WAF1, a potential mediator of p53 tumor suppression. Cell,  1993, 75(4), 817-825.
[http://dx.doi.org/10.1016/0092-8674(93)90500-P] [PMID:  8242752] 
[109] 
Condorelli, F.; Gnemmi, I.; Vallario, A.; Genazzani, A.A.; Canonico, P.L. Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells. Br. J. Pharmacol.,  2008, 153(4), 657-668.
[http://dx.doi.org/10.1038/sj.bjp.0707608] [PMID:  18059320] 
[110] 
Zhao, Y.; Lu, S.; Wu, L.; Chai, G.; Wang, H.; Chen, Y.; Sun, J.; Yu, Y.; Zhou, W.; Zheng, Q.; Wu, M.; Otterson, G.A.; Zhu, W.G. Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1). Mol. Cell. Biol.,  2006, 26(7), 2782-2790.
[http://dx.doi.org/10.1128/MCB.26.7.2782-2790.2006] [PMID:  16537920] 
[111] 
Gui, C.Y.; Ngo, L.; Xu, W.S.; Richon, V.M.; Marks, P.A. Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc. Natl. Acad. Sci. USA,  2004, 101(5), 1241-1246.
[http://dx.doi.org/10.1073/pnas.0307708100] [PMID:  14734806] 
[112] 
Sowa, Y.; Orita, T.; Minamikawa-Hiranabe, S.; Mizuno, T.; Nomura, H.; Sakai, T. Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor. Cancer Res.,  1999, 59(17), 4266-4270.
[PMID:  10485470] 
[113] 
Strait, K.A.; Dabbas, B.; Hammond, E.H.; Warnick, C.T.; Iistrup, S.J.; Ford, C.D. Cell cycle blockade and differentiation of ovarian cancer cells by the histone deacetylase inhibitor trichostatin A are associated with changes in p21, Rb, and Id proteins. Mol. Cancer Ther.,  2002, 1(13), 1181-1190.
[PMID:  12479699] 
[114] 
Greenberg, V.L.; Williams, J.M.; Cogswell, J.P.; Mendenhall, M.; Zimmer, S.G. Histone deacetylase inhibitors promote apoptosis and differential cell cycle arrest in anaplastic thyroid cancer cells. Thyroid,  2001, 11(4), 315-325.
[http://dx.doi.org/10.1089/10507250152039046] [PMID:  11349829] 
[115] 
Flørenes, V.A.; Skrede, M.; Jørgensen, K.; Nesland, J.M. Deacetylase inhibition in malignant melanomas: impact on cell cycle regulation and survival. Melanoma Res.,  2004, 14(3), 173-181.
[http://dx.doi.org/10.1097/01.cmr.0000129576.49313.26] [PMID:  15179185] 
[116] 
Fandy, T.E.; Shankar, S.; Ross, D.D.; Sausville, E.; Srivastava, R.K. Interactive effects of HDAC inhibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma. Neoplasia,  2005, 7(7), 646-657.
[http://dx.doi.org/10.1593/neo.04655] [PMID:  16026644] 
[117] 
Guo, F.; Sigua, C.; Tao, J.; Bali, P.; George, P.; Li, Y.; Wittmann, S.; Moscinski, L.; Atadja, P.; Bhalla, K. Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo-2L/tumor necrosis factor-related apoptosis inducing ligand-induced death inducing signaling complex activity and apoptosis of human acute leukemia cells. Cancer Res.,  2004, 64(7), 2580-2589.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-2629] [PMID:  15059915] 
[118] 
Singh, T.R.; Shankar, S.; Srivastava, R.K. HDAC inhibitors enhance the apoptosis-inducing potential of TRAIL in breast carcinoma. Oncogene,  2005, 24(29), 4609-4623.
[http://dx.doi.org/10.1038/sj.onc.1208585] [PMID:  15897906] 
[119] 
Shankar, S.; Singh, T.R.; Fandy, T.E.; Luetrakul, T.; Ross, D.D.; Srivastava, R.K. Interactive effects of histone deacetylase inhibitors and TRAIL on apoptosis in human leukemia cells: involvement of both death receptor and mitochondrial pathways. Int. J. Mol. Med.,  2005, 16(6), 1125-1138.
[http://dx.doi.org/10.3892/ijmm.16.6.1125] [PMID:  16273296] 
[120] 
Iacomino, G.; Medici, M.C.; Russo, G.L. Valproic acid sensitizes K562 erythroleukemia cells to TRAIL/Apo2L-induced apoptosis. Anticancer Res.,  2008, 28(2A), 855-864.
[PMID:  18507029] 
[121] 
Inoue, S.; Harper, N.; Walewska, R.; Dyer, M.J.; Cohen, G.M. Enhanced Fas-associated death domain recruitment by histone deacetylase inhibitors is critical for the sensitization of chronic lymphocytic leukemia cells to TRAIL-induced apoptosis. Mol. Cancer Ther.,  2009, 8(11), 3088-3097.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0451] [PMID:  19887558] 
[122] 
Matthews, G.M.; Newbold, A.; Johnstone, R.W. Intrinsic and extrinsic apoptotic pathway signaling as determinants of histone deacetylase inhibitor antitumor activity. Adv. Cancer Res.,  2012, 116, 165-197.
[http://dx.doi.org/10.1016/B978-0-12-394387-3.00005-7] [PMID:  23088871] 
[123] 
Mie Lee, Y.; Kim, S.H.; Kim, H.S.; Jin Son, M.; Nakajima, H.; Jeong Kwon, H.; Kim, K.W. Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1alpha activity. Biochem. Biophys. Res. Commun.,  2003, 300(1), 241-246.
[http://dx.doi.org/10.1016/S0006-291X(02)02787-0] [PMID:  12480550] 
[124] 
Sawa, H.; Murakami, H.; Ohshima, Y.; Murakami, M.; Yamazaki, I.; Tamura, Y.; Mima, T.; Satone, A.; Ide, W.; Hashimoto, I.; Kamada, H. Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells. Brain Tumor Pathol.,  2002, 19(2), 77-81.
[http://dx.doi.org/10.1007/BF02478931] [PMID:  12622137] 
[125] 
Sasakawa, Y.; Naoe, Y.; Noto, T.; Inoue, T.; Sasakawa, T.; Matsuo, M.; Manda, T.; Mutoh, S. Antitumor efficacy of FK228, a novel histone deacetylase inhibitor, depends on the effect on expression of angiogenesis factors. Biochem. Pharmacol.,  2003, 66(6), 897-906.
[http://dx.doi.org/10.1016/S0006-2952(03)00411-8] [PMID:  12963476] 
[126] 
Zgouras, D.; Becker, U.; Loitsch, S.; Stein, J. Modulation of angiogenesis-related protein synthesis by valproic acid. Biochem. Biophys. Res. Commun.,  2004, 316(3), 693-697.
[http://dx.doi.org/10.1016/j.bbrc.2004.02.105] [PMID:  15033455] 
[127] 
Heider, U.; Kaiser, M.; Sterz, J.; Zavrski, I.; Jakob, C.; Fleissner, C.; Eucker, J.; Possinger, K.; Sezer, O. Histone deacetylase inhibitors reduce VEGF production and induce growth suppression and apoptosis in human mantle cell lymphoma. Eur. J. Haematol.,  2006, 76(1), 42-50.
[http://dx.doi.org/10.1111/j.1600-0609.2005.00546.x] [PMID:  16343270] 
[128] 
Kim, M.S.; Kwon, H.J.; Lee, Y.M.; Baek, J.H.; Jang, J.E.; Lee, S.W.; Moon, E.J.; Kim, H.S.; Lee, S.K.; Chung, H.Y.; Kim, C.W.; Kim, K.W. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat. Med.,  2001, 7(4), 437-443.
[http://dx.doi.org/10.1038/86507] [PMID:  11283670] 
[129] 
Qian, D.Z.; Kachhap, S.K.; Collis, S.J.; Verheul, H.M.; Carducci, M.A.; Atadja, P.; Pili, R. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res.,  2006, 66(17), 8814-8821.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4598] [PMID:  16951198] 
[130] 
Cheng, H.T.; Hung, W.C. Inhibition of proliferation, sprouting, tube formation and Tie2 signaling of lymphatic endothelial cells by the histone deacetylase inhibitor SAHA. Oncol. Rep.,  2013, 30(2), 961-967.
[http://dx.doi.org/10.3892/or.2013.2523] [PMID:  23754070] 
[131] 
Srivastava, R.K.; Kurzrock, R.; Shankar, S. MS-275 sensitizes TRAIL-resistant breast cancer cells, inhibits angiogenesis and metastasis, and reverses epithelial-mesenchymal transition in vivo. Mol. Cancer Ther.,  2010, 9(12), 3254-3266.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0582] [PMID:  21041383] 
[132] 
Munshi, A.; Kurland, J.F.; Nishikawa, T.; Tanaka, T.; Hobbs, M.L.; Tucker, S.L.; Ismail, S.; Stevens, C.; Meyn, R.E. Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity. Clin. Cancer Res.,  2005, 11(13), 4912-4922.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2088] [PMID:  16000590] 
[133] 
Chen, C.S.; Wang, Y.C.; Yang, H.C.; Huang, P.H.; Kulp, S.K.; Yang, C.C.; Lu, Y.S.; Matsuyama, S.; Chen, C.Y.; Chen, C.S. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation. Cancer Res.,  2007, 67(11), 5318-5327.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3996] [PMID:  17545612] 
[134] 
Zhang, Y.; Carr, T.; Dimtchev, A.; Zaer, N.; Dritschilo, A.; Jung, M. Attenuated DNA damage repair by trichostatin A through BRCA1 suppression. Radiat. Res.,  2007, 168(1), 115-124.
[http://dx.doi.org/10.1667/RR0811.1] [PMID:  17722998] 
[135] 
Adimoolam, S.; Sirisawad, M.; Chen, J.; Thiemann, P.; Ford, J.M.; Buggy, J.J. HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proc. Natl. Acad. Sci. USA,  2007, 104(49), 19482-19487.
[http://dx.doi.org/10.1073/pnas.0707828104] [PMID:  18042714] 
[136] 
Kachhap, S.K.; Rosmus, N.; Collis, S.J.; Kortenhorst, M.S.; Wissing, M.D.; Hedayati, M.; Shabbeer, S.; Mendonca, J.; Deangelis, J.; Marchionni, L.; Lin, J.; Höti, N.; Nortier, J.W.; DeWeese, T.L.; Hammers, H.; Carducci, M.A. Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor. PLoS One,  2010, 5(6)e11208
[http://dx.doi.org/10.1371/journal.pone.0011208] [PMID:  20585447] 
[137] 
Koprinarova, M.; Botev, P.; Russev, G. Histone deacetylase inhibitor sodium butyrate enhances cellular radiosensitivity by inhibiting both DNA nonhomologous end joining and homologous recombination. DNA Repair (Amst.),  2011, 10(9), 970-977.
[http://dx.doi.org/10.1016/j.dnarep.2011.07.003] [PMID:  21824827] 
[138] 
Lee, J.H.; Choy, M.L.; Ngo, L.; Foster, S.S.; Marks, P.A. Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proc. Natl. Acad. Sci. USA,  2010, 107(33), 14639-14644.
[http://dx.doi.org/10.1073/pnas.1008522107] [PMID:  20679231] 
[139] 
Rosato, R.R.; Almenara, J.A.; Grant, S. The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1. Cancer Res.,  2003, 63(13), 3637-3645.
[PMID:  12839953] 
[140] 
Yu, C.; Subler, M.; Rahmani, M.; Reese, E.; Krystal, G.; Conrad, D.; Dent, P.; Grant, S. Induction of apoptosis in BCR/ABL+ cells by histone deacetylase inhibitors involves reciprocal effects on the RAF/MEK/ERK and JNK pathways. Cancer Biol. Ther.,  2003, 2(5), 544-551.
[http://dx.doi.org/10.4161/cbt.2.5.454] [PMID:  14614324] 
[141] 
Butler, L.M.; Zhou, X.; Xu, W.S.; Scher, H.I.; Rifkind, R.A.; Marks, P.A.; Richon, V.M. The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc. Natl. Acad. Sci. USA,  2002, 99(18), 11700-11705.
[http://dx.doi.org/10.1073/pnas.182372299] [PMID:  12189205] 
[142] 
Ungerstedt, J.; Du, Y.; Zhang, H.; Nair, D.; Holmgren, A. In vivo redox state of human thioredoxin and redox shift by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Free Radic. Biol. Med.,  2012, 53(11), 2002-2007.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.09.019] [PMID:  23010496] 
[143] 
Mitra, A.; Mishra, L.; Li, S. EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget,  2015, 6(13), 10697-10711.
[http://dx.doi.org/10.18632/oncotarget.4037] [PMID:  25986923] 
[144] 
Tam, W.L.; Weinberg, R.A. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med.,  2013, 19(11), 1438-1449.
[http://dx.doi.org/10.1038/nm.3336] [PMID:  24202396] 
[145] 
Bruzzese, F.; Leone, A.; Rocco, M.; Carbone, C.; Piro, G.; Caraglia, M.; Di Gennaro, E.; Budillon, A. HDAC inhibitor vorinostat enhances the antitumor effect of gefitinib in squamous cell carcinoma of head and neck by modulating ErbB receptor expression and reverting EMT. J. Cell. Physiol.,  2011, 226(9), 2378-2390.
[http://dx.doi.org/10.1002/jcp.22574] [PMID:  21660961] 
[146] 
Mateen, S.; Raina, K.; Agarwal, C.; Chan, D.; Agarwal, R. Silibinin synergizes with histone deacetylase and DNA methyltransferase inhibitors in upregulating E-cadherin expression together with inhibition of migration and invasion of human non-small cell lung cancer cells. J. Pharmacol. Exp. Ther.,  2013, 345(2), 206-214.
[http://dx.doi.org/10.1124/jpet.113.203471] [PMID:  23461975] 
[147] 
Meng, F.; Sun, G.; Zhong, M.; Yu, Y.; Brewer, M.A. Anticancer efficacy of cisplatin and trichostatin A or 5-aza-2′-deoxycytidine on ovarian cancer. Br. J. Cancer,  2013, 108(3), 579-586.
[http://dx.doi.org/10.1038/bjc.2013.10] [PMID:  23370212] 
[148] 
Nalls, D.; Tang, S.N.; Rodova, M.; Srivastava, R.K.; Shankar, S. Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells. PLoS One,  2011, 6(8)e24099
[http://dx.doi.org/10.1371/journal.pone.0024099] [PMID:  21909380] 
[149] 
Rhodes, L.V.; Tate, C.R.; Segar, H.C.; Burks, H.E.; Phamduy, T.B.; Hoang, V.; Elliott, S.; Gilliam, D.; Pounder, F.N.; Anbalagan, M.; Chrisey, D.B.; Rowan, B.G.; Burow, M.E.; Collins-Burow, B.M. Suppression of triple-negative breast cancer metastasis by pan-DAC inhibitor panobinostat via inhibition of ZEB family of EMT master regulators. Breast Cancer Res. Treat.,  2014, 145(3), 593-604.
[http://dx.doi.org/10.1007/s10549-014-2979-6] [PMID:  24810497] 
[150] 
Wang, X.; Xu, J.; Wang, H.; Wu, L.; Yuan, W.; Du, J.; Cai, S.; Trichostatin, A. Trichostatin A, a histone deacetylase inhibitor, reverses epithelial-mesenchymal transition in colorectal cancer SW480 and prostate cancer PC3 cells. Biochem. Biophys. Res. Commun.,  2015, 456(1), 320-326.
[http://dx.doi.org/10.1016/j.bbrc.2014.11.079] [PMID:  25434997] 
[151] 
Kouzarides, T. Chromatin modifications and their function. Cell,  2007, 128, 693-705.
[152] 
Fortschegger, K.; Shiekhattar, R. Plant homeodomain fingers form a helping hand for transcription. Epigenetics,  2011, 6(1), 4-8.
[http://dx.doi.org/10.4161/epi.6.1.13297] [PMID:  20818169] 
[153] 
Krishnan, S.; Horowitz, S.; Trievel, R.C. Structure and function of histone H3 lysine 9 methyltransferases and demethylases. ChemBioChem,  2011, 12(2), 254-263.
[http://dx.doi.org/10.1002/cbic.201000545] [PMID:  21243713] 
[154] 
Walport, L.J.; Hopkinson, R.J.; Schofield, C.J. Mechanisms of human histone and nucleic acid demethylases. Curr. Opin. Chem. Biol.,  2012, 16(5-6), 525-534.
[http://dx.doi.org/10.1016/j.cbpa.2012.09.015] [PMID:  23063108] 
[155] 
Klose, R.J.; Kallin, E.M.; Zhang, Y. JmjC-domain-containing proteins and histone demethylation. Nat. Rev. Genet.,  2006, 7(9), 715-727.
[http://dx.doi.org/10.1038/nrg1945] [PMID:  16983801] 
[156] 
Tsukada, Y.; Fang, J.; Erdjument-Bromage, H.; Warren, M.E.; Borchers, C.H.; Tempst, P.; Zhang, Y. Histone demethylation by a family of JmjC domain-containing proteins. Nature,  2006, 439(7078), 811-816.
[http://dx.doi.org/10.1038/nature04433] [PMID:  16362057] 
[157] 
Shi, Y. Histone lysine demethylases: emerging roles in development, physiology and disease. Nat. Rev. Genet.,  2007, 8(11), 829-833.
[http://dx.doi.org/10.1038/nrg2218] [PMID:  17909537] 
[158] 
Hoffmann, I.; Roatsch, M.; Schmitt, M.L.; Carlino, L.; Pippel, M.; Sippl, W.; Jung, M. The role of histone demethylases in cancer therapy. Mol. Oncol.,  2012, 6(6), 683-703.
[http://dx.doi.org/10.1016/j.molonc.2012.07.004] [PMID:  22902149] 
[159] 
Højfeldt, J.W.; Agger, K.; Helin, K. Histone lysine demethylases as targets for anticancer therapy. Nat. Rev. Drug Discov.,  2013, 12(12), 917-930.
[http://dx.doi.org/10.1038/nrd4154] [PMID:  24232376] 
[160] 
Crea, F.; Sun, L.; Mai, A.; Chiang, Y.T.; Farrar, W.L.; Danesi, R.; Helgason, C.D. The emerging role of histone lysine demethylases in prostate cancer. Mol. Cancer,  2012, 11, 52-52.
[http://dx.doi.org/10.1186/1476-4598-11-52] [PMID:  22867098] 
[161] 
Shmakova, A.; Batie, M.; Druker, J.; Rocha, S. Chromatin and oxygen sensing in the context of JmjC histone demethylases. Biochem. J.,  2014, 462(3), 385-395.
[http://dx.doi.org/10.1042/BJ20140754] [PMID:  25145438] 
[162] 
Wagner, K.W.; Alam, H.; Dhar, S.S.; Giri, U.; Li, N.; Wei, Y.; Giri, D.; Cascone, T.; Kim, J-H.; Ye, Y.; Multani, A.S.; Chan, C-H.; Erez, B.; Saigal, B.; Chung, J.; Lin, H-K.; Wu, X.; Hung, M-C.; Heymach, J.V.; Lee, M.G. KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling. J. Clin. Invest.,  2013, 123(12), 5231-5246.
[http://dx.doi.org/10.1172/JCI68642] [PMID:  24200691] 
[163] 
Liu, H.; Liu, L.; Holowatyj, A.; Jiang, Y.; Yang, Z-Q. Integrated genomic and functional analyses of histone demethylases identify oncogenic KDM2A isoform in breast cancer. Mol. Carcinog.,  2016, 55(5), 977-990.
[http://dx.doi.org/10.1002/mc.22341] [PMID:  26207617] 
[164] 
Huang, Y.; Liu, Y.; Yu, L.; Chen, J.; Hou, J.; Cui, L.; Ma, D.; Lu, W. Histone demethylase KDM2A promotes tumor cell growth and migration in gastric cancer. Tumour Biol.,  2015, 36(1), 271-278.
[http://dx.doi.org/10.1007/s13277-014-2630-5] [PMID:  25245333] 
[165] 
Frescas, D.; Guardavaccaro, D.; Bassermann, F.; Koyama-Nasu, R.; Pagano, M. JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes. Nature,  2007, 450(7167), 309-313.
[http://dx.doi.org/10.1038/nature06255] [PMID:  17994099] 
[166] 
He, J.; Nguyen, A.T.; Zhang, Y. KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia. Blood,  2011, 117(14), 3869-3880.
[http://dx.doi.org/10.1182/blood-2010-10-312736] [PMID:  21310926] 
[167] 
Tzatsos, A.; Paskaleva, P.; Ferrari, F.; Deshpande, V.; Stoykova, S.; Contino, G.; Wong, K-K.; Lan, F.; Trojer, P.; Park, P.J.; Bardeesy, N. KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs. J. Clin. Invest.,  2013, 123(2), 727-739.
[http://dx.doi.org/10.1172/JCI64535] [PMID:  23321669] 
[168] 
Kottakis, F.; Polytarchou, C.; Foltopoulou, P.; Sanidas, I.; Kampranis, S.C.; Tsichlis, P.N. FGF-2 regulates cell proliferation, migration, and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway. Mol. Cell,  2011, 43(2), 285-298.
[http://dx.doi.org/10.1016/j.molcel.2011.06.020] [PMID:  21777817] 
[169] 
Wade, M.A.; Jones, D.; Wilson, L.; Stockley, J.; Coffey, K.; Robson, C.N.; Gaughan, L. The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer. Nucleic Acids Res.,  2015, 43(1), 196-207.
[http://dx.doi.org/10.1093/nar/gku1298] [PMID:  25488809] 
[170] 
Qi, J.; Nakayama, K.; Cardiff, R.D.; Borowsky, A.D.; Kaul, K.; Williams, R.; Krajewski, S.; Mercola, D.; Carpenter, P.M.; Bowtell, D.; Ronai, Z.A. Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine phenotype and neuroendocrine prostate tumors. Cancer Cell,  2010, 18(1), 23-38.
[http://dx.doi.org/10.1016/j.ccr.2010.05.024] [PMID:  20609350] 
[171] 
Uemura, M.; Yamamoto, H.; Takemasa, I.; Mimori, K.; Hemmi, H.; Mizushima, T.; Ikeda, M.; Sekimoto, M.; Matsuura, N.; Doki, Y.; Mori, M. Jumonji domain containing 1A is a novel prognostic marker for colorectal cancer: in vivo identification from hypoxic tumor cells. Clin. Cancer Res.,  2010, 16(18), 4636-4646.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0407] [PMID:  20823141] 
[172] 
Guo, X.; Shi, M.; Sun, L.; Wang, Y.; Gui, Y.; Cai, Z.; Duan, X. The expression of histone demethylase JMJD1A in renal cell carcinoma. Neoplasma,  2011, 58(2), 153-157.
[http://dx.doi.org/10.4149/neo_2011_02_153] [PMID:  21275466] 
[173] 
Yamada, D.; Kobayashi, S.; Yamamoto, H.; Tomimaru, Y.; Noda, T.; Uemura, M.; Wada, H.; Marubashi, S.; Eguchi, H.; Tanemura, M.; Doki, Y.; Mori, M.; Nagano, H. Role of the hypoxia-related gene, JMJD1A, in hepatocellular carcinoma: clinical impact on recurrence after hepatic resection. Ann. Surg. Oncol.,  2012, 19(Suppl. 3), S355-S364.
[http://dx.doi.org/10.1245/s10434-011-1797-x] [PMID:  21607773] 
[174] 
Kauffman, E.C.; Robinson, B.D.; Downes, M.J.; Powell, L.G.; Lee, M.M.; Scherr, D.S.; Gudas, L.J.; Mongan, N.P. Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer. Mol. Carcinog.,  2011, 50(12), 931-944.
[http://dx.doi.org/10.1002/mc.20758] [PMID:  21400613] 
[175] 
Ye, Q.; Holowatyj, A.; Wu, J.; Liu, H.; Zhang, L.; Suzuki, T.; Yang, Z-Q. Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer. Am. J. Cancer Res.,  2015, 5(4), 1519-1530.
[PMID:  26101715] 
[176] 
Pryor, J.G.; Brown-Kipphut, B.A.; Iqbal, A.; Scott, G.A. Microarray comparative genomic hybridization detection of copy number changes in desmoplastic melanoma and malignant peripheral nerve sheath tumor. Am. J. Dermatopathol.,  2011, 33(8), 780-785.
[http://dx.doi.org/10.1097/DAD.0b013e31820dfcbf] [PMID:  21785329] 
[177] 
Liu, G.; Bollig-Fischer, A.; Kreike, B.; van de Vijver, M.J.; Abrams, J.; Ethier, S.P.; Yang, Z-Q. Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer. Oncogene,  2009, 28(50), 4491-4500.
[http://dx.doi.org/10.1038/onc.2009.297] [PMID:  19784073] 
[178] 
Uimonen, K.; Merikallio, H.; Pääkkö, P.; Harju, T.; Mannermaa, A.; Palvimo, J.; Kosma, V.M.; Soini, Y. GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma. Histol. Histopathol.,  2014, 29(6), 797-804.
[http://dx.doi.org/10.14670/HH-29.797] [PMID:  24371038] 
[179] 
Yang, Z-Q.; Imoto, I.; Fukuda, Y.; Pimkhaokham, A.; Shimada, Y.; Imamura, M.; Sugano, S.; Nakamura, Y.; Inazawa, J. Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines. Cancer Res.,  2000, 60(17), 4735-4739.
[PMID:  10987278] 
[180] 
Sun, L-L.; Wu, J-Y.; Wu, Z-Y.; Shen, J-H.; Xu, X-E.; Chen, B.; Wang, S-H.; Li, E-M.; Xu, L-Y. A three-gene signature and clinical outcome in esophageal squamous cell carcinoma. Int. J. Cancer,  2015, 136(6), E569-E577.
[http://dx.doi.org/10.1002/ijc.29211] [PMID:  25220908] 
[181] 
Ozaki, Y.; Fujiwara, K.; Ikeda, M.; Ozaki, T.; Terui, T.; Soma, M.; Inazawa, J.; Nagase, H. The oncogenic role of GASC1 in chemically induced mouse skin cancer. Mamm. Genome,  2015, 26(11-12), 591-597.
[http://dx.doi.org/10.1007/s00335-015-9592-9] [PMID:  26248577] 
[182] 
Suikki, H.E.; Kujala, P.M.; Tammela, T.L.J.; van Weerden, W.M.; Vessella, R.L.; Visakorpi, T. Genetic alterations and changes in expression of histone demethylases in prostate cancer. Prostate,  2010, 70(8), 889-898.
[http://dx.doi.org/10.1002/pros.21123] [PMID:  20127736] 
[183] 
Vinatzer, U.; Gollinger, M.; Müllauer, L.; Raderer, M.; Chott, A.; Streubel, B. Mucosa-associated lymphoid tissue lymphoma: novel translocations including rearrangements of ODZ2, JMJD2C, and CNN3. Clin. Cancer Res.,  2008, 14(20), 6426-6431.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0702] [PMID:  18927281] 
[184] 
Ehrbrecht, A.; Müller, U.; Wolter, M.; Hoischen, A.; Koch, A.; Radlwimmer, B.; Actor, B.; Mincheva, A.; Pietsch, T.; Lichter, P.; Reifenberger, G.; Weber, R.G. Comprehensive genomic analysis of desmoplastic medulloblastomas: identification of novel amplified genes and separate evaluation of the different histological components. J. Pathol.,  2006, 208(4), 554-563.
[http://dx.doi.org/10.1002/path.1925] [PMID:  16400626] 
[185] 
Teng, Y-C.; Lee, C-F.; Li, Y-S.; Chen, Y-R.; Hsiao, P-W.; Chan, M-Y.; Lin, F-M.; Huang, H-D.; Chen, Y-T.; Jeng, Y-M.; Hsu, C-H.; Yan, Q.; Tsai, M-D.; Juan, L-J. Histone demethylase RBP2 promotes lung tumorigenesis and cancer metastasis. Cancer Res.,  2013, 73(15), 4711-4721.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3165] [PMID:  23722541] 
[186] 
Wang, G.G.; Song, J.; Wang, Z.; Dormann, H.L.; Casadio, F.; Li, H.; Luo, J-L.; Patel, D.J.; Allis, C.D. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger. Nature,  2009, 459(7248), 847-851.
[http://dx.doi.org/10.1038/nature08036] [PMID:  19430464] 
[187] 
Vogt, T.; Kroiss, M.; McClelland, M.; Gruss, C.; Becker, B.; Bosserhoff, A.K.; Rumpler, G.; Bogenrieder, T.; Landthaler, M.; Stolz, W. Deficiency of a novel retinoblastoma binding protein 2-homolog is a consistent feature of sporadic human melanoma skin cancer. Lab. Invest.,  1999, 79(12), 1615-1627.
[PMID:  10616211] 
[188] 
Roesch, A.; Becker, B.; Meyer, S.; Wild, P.; Hafner, C.; Landthaler, M.; Vogt, T. Retinoblastoma-binding protein 2-homolog 1: a retinoblastoma-binding protein downregulated in malignant melanomas. Mod. Pathol.,  2005, 18(9), 1249-1257.
[http://dx.doi.org/10.1038/modpathol.3800413] [PMID:  15803180] 
[189] 
Yamamoto, S.; Wu, Z.; Russnes, H.G.; Takagi, S.; Peluffo, G.; Vaske, C.; Zhao, X.; Moen Vollan, H.K.; Maruyama, R.; Ekram, M.B.; Sun, H.; Kim, J.H.; Carver, K.; Zucca, M.; Feng, J.; Almendro, V.; Bessarabova, M.; Rueda, O.M.; Nikolsky, Y.; Caldas, C.; Liu, X.S.; Polyak, K. JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer Cell,  2014, 25(6), 762-777.
[http://dx.doi.org/10.1016/j.ccr.2014.04.024] [PMID:  24937458] 
[190] 
Xiang, Y.; Zhu, Z.; Han, G.; Ye, X.; Xu, B.; Peng, Z.; Ma, Y.; Yu, Y.; Lin, H.; Chen, A.P.; Chen, C.D. JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer. Proc. Natl. Acad. Sci. USA,  2007, 104(49), 19226-19231.
[http://dx.doi.org/10.1073/pnas.0700735104] [PMID:  18048344] 
[191] 
Hayami, S.; Kelly, J.D.; Cho, H-S.; Yoshimatsu, M.; Unoki, M.; Tsunoda, T.; Field, H.I.; Neal, D.E.; Yamaue, H.; Ponder, B.A.J.; Nakamura, Y.; Hamamoto, R. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int. J. Cancer,  2011, 128(3), 574-586.
[http://dx.doi.org/10.1002/ijc.25349] [PMID:  20333681] 
[192] 
Jangravi, Z.; Tabar, M.S.; Mirzaei, M.; Parsamatin, P.; Vakilian, H.; Alikhani, M.; Shabani, M.; Haynes, P.A.; Goodchild, A.K.; Gourabi, H.; Baharvand, H.; Salekdeh, G.H. Two splice variants of Y chromosome-Located lysine-specific demethylase 5D have distinct function in prostate cancer Cell line (DU-145). J. Proteome Res.,  2015, 14(9), 3492-3502.
[http://dx.doi.org/10.1021/acs.jproteome.5b00333] [PMID:  26215926] 
[193] 
Stein, J.; Majores, M.; Rohde, M.; Lim, S.; Schneider, S.; Krappe, E.; Ellinger, J.; Dietel, M.; Stephan, C.; Jung, K.; Perner, S.; Kristiansen, G.; Kirfel, J. KDM5C is overexpressed in prostate cancer and is a prognostic marker for prostate-specific antigen-relapse following radical prostatectomy. Am. J. Pathol.,  2014, 184(9), 2430-2437.
[http://dx.doi.org/10.1016/j.ajpath.2014.05.022] [PMID:  25016185] 
[194] 
Dalgliesh, G.L.; Furge, K.; Greenman, C.; Chen, L.; Bignell, G.; Butler, A.; Davies, H.; Edkins, S.; Hardy, C.; Latimer, C.; Teague, J.; Andrews, J.; Barthorpe, S.; Beare, D.; Buck, G.; Campbell, P.J.; Forbes, S.; Jia, M.; Jones, D.; Knott, H.; Kok, C.Y.; Lau, K.W.; Leroy, C.; Lin, M-L.; McBride, D.J.; Maddison, M.; Maguire, S.; McLay, K.; Menzies, A.; Mironenko, T.; Mulderrig, L.; Mudie, L.; O’Meara, S.; Pleasance, E.; Rajasingham, A.; Shepherd, R.; Smith, R.; Stebbings, L.; Stephens, P.; Tang, G.; Tarpey, P.S.; Turrell, K.; Dykema, K.J.; Khoo, S.K.; Petillo, D.; Wondergem, B.; Anema, J.; Kahnoski, R.J.; Teh, B.T.; Stratton, M.R.; Futreal, P.A. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature,  2010, 463(7279), 360-363.
[http://dx.doi.org/10.1038/nature08672] [PMID:  20054297] 
[195] 
Liu, J.; Lee, W.; Jiang, Z.; Chen, Z.; Jhunjhunwala, S.; Haverty, P.M.; Gnad, F.; Guan, Y.; Gilbert, H.N.; Stinson, J.; Klijn, C.; Guillory, J.; Bhatt, D.; Vartanian, S.; Walter, K.; Chan, J.; Holcomb, T.; Dijkgraaf, P.; Johnson, S.; Koeman, J.; Minna, J.D.; Gazdar, A.F.; Stern, H.M.; Hoeflich, K.P.; Wu, T.D.; Settleman, J.; de Sauvage, F.J.; Gentleman, R.C.; Neve, R.M.; Stokoe, D.; Modrusan, Z.; Seshagiri, S.; Shames, D.S.; Zhang, Z. Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events. Genome Res.,  2012, 22(12), 2315-2327.
[http://dx.doi.org/10.1101/gr.140988.112] [PMID:  23033341] 
[196] 
Nakata, E.; Yukimachi, Y.; Kariyazono, H.; Im, S.; Abe, C.; Uto, Y.; Maezawa, H.; Hashimoto, T.; Okamoto, Y.; Hori, H. Design of a bioreductively-activated fluorescent pH probe for tumor hypoxia imaging. Bioorg. Med. Chem.,  2009, 17(19), 6952-6958.
[http://dx.doi.org/10.1016/j.bmc.2009.08.037] [PMID:  19736018] 
[197] 
van Haaften, G.; Dalgliesh, G.L.; Davies, H.; Chen, L.; Bignell, G.; Greenman, C.; Edkins, S.; Hardy, C.; O’Meara, S.; Teague, J.; Butler, A.; Hinton, J.; Latimer, C.; Andrews, J.; Barthorpe, S.; Beare, D.; Buck, G.; Campbell, P.J.; Cole, J.; Forbes, S.; Jia, M.; Jones, D.; Kok, C.Y.; Leroy, C.; Lin, M-L.; McBride, D.J.; Maddison, M.; Maquire, S.; McLay, K.; Menzies, A.; Mironenko, T.; Mulderrig, L.; Mudie, L.; Pleasance, E.; Shepherd, R.; Smith, R.; Stebbings, L.; Stephens, P.; Tang, G.; Tarpey, P.S.; Turner, R.; Turrell, K.; Varian, J.; West, S.; Widaa, S.; Wray, P.; Collins, V.P.; Ichimura, K.; Law, S.; Wong, J.; Yuen, S.T.; Leung, S.Y.; Tonon, G.; DePinho, R.A.; Tai, Y-T.; Anderson, K.C.; Kahnoski, R.J.; Massie, A.; Khoo, S.K.; Teh, B.T.; Stratton, M.R.; Futreal, P.A. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat. Genet.,  2009, 41(5), 521-523.
[http://dx.doi.org/10.1038/ng.349] [PMID:  19330029] 
[198] 
Ibragimova, I.; Maradeo, M.E.; Dulaimi, E.; Cairns, P. Aberrant promoter hypermethylation of PBRM1, BAP1, SETD2, KDM6A and other chromatin-modifying genes is absent or rare in clear cell RCC. Epigenetics,  2013, 8(5), 486-493.
[http://dx.doi.org/10.4161/epi.24552] [PMID:  23644518] 
[199] 
Smith, E.M.; Boyd, K.; Davies, F.E. The potential role of epigenetic therapy in multiple myeloma. Br. J. Haematol.,  2010, 148(5), 702-713.
[http://dx.doi.org/10.1111/j.1365-2141.2009.07976.x] [PMID:  19912222] 
[200] 
Gui, Y.; Guo, G.; Huang, Y.; Hu, X.; Tang, A.; Gao, S.; Wu, R.; Chen, C.; Li, X.; Zhou, L.; He, M.; Li, Z.; Sun, X.; Jia, W.; Chen, J.; Yang, S.; Zhou, F.; Zhao, X.; Wan, S.; Ye, R.; Liang, C.; Liu, Z.; Huang, P.; Liu, C.; Jiang, H.; Wang, Y.; Zheng, H.; Sun, L.; Liu, X.; Jiang, Z.; Feng, D.; Chen, J.; Wu, S.; Zou, J.; Zhang, Z.; Yang, R.; Zhao, J.; Xu, C.; Yin, W.; Guan, Z.; Ye, J.; Zhang, H.; Li, J.; Kristiansen, K.; Nickerson, M.L.; Theodorescu, D.; Li, Y.; Zhang, X.; Li, S.; Wang, J.; Yang, H.; Wang, J.; Cai, Z. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat. Genet.,  2011, 43(9), 875-878.
[http://dx.doi.org/10.1038/ng.907] [PMID:  21822268] 
[201] 
Ntziachristos, P.; Tsirigos, A.; Welstead, G.G.; Trimarchi, T.; Bakogianni, S.; Xu, L.; Loizou, E.; Holmfeldt, L.; Strikoudis, A.; King, B.; Mullenders, J.; Becksfort, J.; Nedjic, J.; Paietta, E.; Tallman, M.S.; Rowe, J.M.; Tonon, G.; Satoh, T.; Kruidenier, L.; Prinjha, R.; Akira, S.; Van Vlierberghe, P.; Ferrando, A.A.; Jaenisch, R.; Mullighan, C.G.; Aifantis, I.  Contrasting roles of histone 3 lysine 27 demethylases
in acute lymphoblastic leukaemia. Nat. Lond. U K
514, 2014, 513-517.
[PMID: 25132549] [10.1038/nature13605]
[202] 
Kim, J-H.; Sharma, A.; Dhar, S.S.; Lee, S-H.; Gu, B.; Chan, C-H.; Lin, H-K.; Lee, M.G. UTX and MLL4 coordinately regulate transcriptional programs for cell proliferation and invasiveness in breast cancer cells. Cancer Res.,  2014, 74(6), 1705-1717.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-1896] [PMID:  24491801] 
[203] 
Ma, J.; Wang, N.; Zhang, Y.; Wang, C.; Ge, T.; Jin, H.; Deng, X.; Huo, X.; Gu, D.; Ge, Z.; Chu, W.; Jiang, L.; Qin, W. KDM6B elicits cell apoptosis by promoting nuclear translocation of FOXO1 in Non-Small Cell Lung Cancer. Cell. Physiol. Biochem.,  2015, 37(1), 201-213.
[http://dx.doi.org/10.1159/000430345] [PMID:  26303949] 
[204] 
Zhang, P-P.; Wang, X.L.; Zhao, W.; Qi, B.; Yang, Q.; Wan, H-Y.; Shuang, Z.Y.; Liu, M.; Li, X.; Li, S.; Tang, H. DNA methylation-mediated repression of miR-941 enhances lysine (K)-specific demethylase 6B expression in hepatoma cells. J. Biol. Chem.,  2014, 289(35), 24724-24735.
[http://dx.doi.org/10.1074/jbc.M114.567818] [PMID:  25049231] 
[205] 
Lin, T.Y.; Cheng, Y.C.; Yang, H.C.; Lin, W.C.; Wang, C.C.; Lai, P.L.; Shieh, S.Y. Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERK-JMJD3-p16(INK4a) signaling axis. Oncogene,  2012, 31(27), 3287-3297.
[http://dx.doi.org/10.1038/onc.2011.491] [PMID:  22020331] 
[206] 
Komiya, K.; Sueoka-Aragane, N.; Sato, A.; Hisatomi, T.; Sakuragi, T.; Mitsuoka, M.; Sato, T.; Hayashi, S.; Izumi, H.; Tsuneoka, M.; Sueoka, E. Expression of Mina53, a novel c-Myc target gene, is a favorable prognostic marker in early stage lung cancer. Lung Cancer,  2010, 69(2), 232-238.
[http://dx.doi.org/10.1016/j.lungcan.2009.10.010] [PMID:  19914733] 
[207] 
Suzuki, C.; Takahashi, K.; Hayama, S.; Ishikawa, N.; Kato, T.; Ito, T.; Tsuchiya, E.; Nakamura, Y.; Daigo, Y. Identification of Myc-associated protein with JmjC domain as a novel therapeutic target oncogene for lung cancer. Mol. Cancer Ther.,  2007, 6(2), 542-551.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0659] [PMID:  17308053] 
[208] 
Wagner, E.K.; Nath, N.; Flemming, R.; Feltenberger, J.B.; Denu, J.M. Identification and characterization of small molecule inhibitors of a plant homeodomain finger. Biochemistry,  2012, 51(41), 8293-8306.
[http://dx.doi.org/10.1021/bi3009278] [PMID:  22994852] 
[209] 
McDonough, M.A.; Loenarz, C.; Chowdhury, R.; Clifton, I.J.; Schofield, C.J. Structural studies on human 2-oxoglutarate dependent oxygenases. Curr. Opin. Struct. Biol.,  2010, 20(6), 659-672.
[http://dx.doi.org/10.1016/j.sbi.2010.08.006] [PMID:  20888218] 
[210] 
Aik, W.; McDonough, M.A.; Thalhammer, A.; Chowdhury, R.; Schofield, C.J. Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases. Curr. Opin. Struct. Biol.,  2012, 22(6), 691-700.
[http://dx.doi.org/10.1016/j.sbi.2012.10.001] [PMID:  23142576] 
[211] 
Schofield, C.J.; Ratcliffe, P.J. Oxygen sensing by HIF hydroxylases. Nat. Rev. Mol. Cell Biol.,  2004, 5(5), 343-354.
[http://dx.doi.org/10.1038/nrm1366] [PMID:  15122348] 
[212] 
Rose, N.R.; McDonough, M.A.; King, O.N.F.; Kawamura, A.; Schofield, C.J. Inhibition of 2-oxoglutarate dependent oxygenases. Chem. Soc. Rev.,  2011, 40(8), 4364-4397.
[http://dx.doi.org/10.1039/c0cs00203h] [PMID:  21390379] 
[213] 
Cunliffe, C.J.; Franklin, T.J.; Hales, N.J.; Hill, G.B. Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analogue N-oxaloglycine and its derivatives. J. Med. Chem.,  1992, 35(14), 2652-2658.
[http://dx.doi.org/10.1021/jm00092a016] [PMID:  1321909] 
[214] 
Opocher, G.; Schiavi, F. Functional consequences of succinate dehydrogenase mutations. Endocr. Pract.,  2011, 17(Suppl. 3), 64-71.
[http://dx.doi.org/10.4158/EP11070.RA] [PMID:  21742608] 
[215] 
Dang, L.; White, D.W.; Gross, S.; Bennett, B.D.; Bittinger, M.A.; Driggers, E.M.; Fantin, V.R.; Jang, H-G.; Jin, S.; Keenan, M.C.; Marks, K.M.; Prins, R.M.; Ward, P.S.; Yen, K.E.; Liau, L.M.; Rabinowitz, J.D.; Cantley, L.C.; Thompson, C.B.; Vander Heiden, M.G.; Su, S.M. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature,  2009, 462(7274), 739-744.
[216] 
Losman, J-A.; Looper, R.E.; Koivunen, S.; Lee, S.; Schneider, R.K.; McMahon, C.; Cowley, G.S.; Root, D.E.; Ebert, B.L.; Kaelin, W.G., Jr R)-2-Hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science,  2013, 1621-1625.
[http://dx.doi.org/10.1126/science.1231677] [PMID: 23393090] 
[217] 
Puistola, U.; Turpeenniemi-Hujanen, T.M.; Myllylä, R.; Kivirikko, K.I. Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. Biochim. Biophys. Acta,  1980, 611(1), 40-50.
[http://dx.doi.org/10.1016/0005-2744(80)90040-6] [PMID:  6766066] 
[218] 
Myllylä, R.; Tuderman, L.; Kivirikko, K.I. Mechanism of the prolyl hydroxylase reaction. 2. Kinetic analysis of the reaction sequence. Eur. J. Biochem.,  1977, 80(2), 349-357.
[http://dx.doi.org/10.1111/j.1432-1033.1977.tb11889.x] [PMID:  200425] 
[219] 
Xiao, M.; Yang, H.; Xu, W.; Ma, S.; Lin, H.; Zhu, H.; Liu, L.; Liu, Y.; Yang, C.; Xu, Y.; Zhao, S.; Ye, D.; Xiong, Y.; Guan, K-L. Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev.,  2012, 26(12), 1326-1338.
[http://dx.doi.org/10.1101/gad.191056.112] [PMID:  22677546] 
[220] 
Rose, N.R.; Ng, S.S.; Mecinović, J.; Liénard, B.M.R.; Bello, S.H.; Sun, Z.; McDonough, M.A.; Oppermann, U.; Schofield, C.J. Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases. J. Med. Chem.,  2008, 51(22), 7053-7056.
[http://dx.doi.org/10.1021/jm800936s] [PMID:  18942826] 
[221] 
Couture, J-F.; Collazo, E.; Ortiz-Tello, P.A.; Brunzelle, J.S.; Trievel, R.C. Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase. Nat. Struct. Mol. Biol.,  2007, 14(8), 689-695.
[http://dx.doi.org/10.1038/nsmb1273] [PMID:  17589523] 
[222] 
MacKenzie, E.D.; Selak, M.A.; Tennant, D.A.; Payne, L.J.; Crosby, S.; Frederiksen, C.M.; Watson, D.G.; Gottlieb, E. Cell-permeating α-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol. Cell. Biol.,  2007, 27(9), 3282-3289.
[http://dx.doi.org/10.1128/MCB.01927-06] [PMID:  17325041] 
[223] 
Hamada, S.; Suzuki, T.; Mino, K.; Koseki, K.; Oehme, F.; Flamme, I.; Ozasa, H.; Itoh, Y.; Ogasawara, D.; Komaarashi, H.; Kato, A.; Tsumoto, H.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Miyata, N. Design, synthesis, enzyme-inhibitory activity, and effect on human cancer cells of a novel series of jumonji domain-containing protein 2 histone demethylase inhibitors. J. Med. Chem.,  2010, 53(15), 5629-5638.
[http://dx.doi.org/10.1021/jm1003655] [PMID:  20684604] 
[224] 
Suzuki, T.; Ozasa, H.; Itoh, Y.; Zhan, P.; Sawada, H.; Mino, K.; Walport, L.; Ohkubo, R.; Kawamura, A.; Yonezawa, M.; Tsukada, Y.; Tumber, A.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Schofield, C.J.; Miyata, N. Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity. J. Med. Chem.,  2013, 56(18), 7222-7231.
[http://dx.doi.org/10.1021/jm400624b] [PMID:  23964788] 
[225] 
Rose, N.R.; Woon, E.C.Y.; Tumber, A.; Walport, L.J.; Chowdhury, R.; Li, X.S.; King, O.N.F.; Lejeune, C.; Ng, S.S.; Krojer, T.; Chan, M.C.; Rydzik, A.M.; Hopkinson, R.J.; Che, K.H.; Daniel, M.; Strain-Damerell, C.; Gileadi, C.; Kochan, G.; Leung, I.K.H.; Dunford, J.; Yeoh, K.K.; Ratcliffe, P.J.; Burgess-Brown, N.; von Delft, F.; Muller, S.; Marsden, B.; Brennan, P.E.; McDonough, M.A.; Oppermann, U.; Klose, R.J.; Schofield, C.J.; Kawamura, A. Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases. J. Med. Chem.,  2012, 55(14), 6639-6643.
[http://dx.doi.org/10.1021/jm300677j] [PMID:  22724510] 
[226] 
Luo, X.; Liu, Y.; Kubicek, S.; Myllyharju, J.; Tumber, A.; Ng, S.; Che, K-H.; Podoll, J.; Heightman, T.D.; Oppermann, U.; Schreiber, S.L.; Wang, X. A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases. J. Am. Chem. Soc.,  2011, 133(24), 9451-9456.
[http://dx.doi.org/10.1021/ja201597b] [PMID:  21585201] 
[227] 
Itoh, Y.; Sawada, H.; Suzuki, M.; Tojo, T.; Sasaki, R.; Hasegawa, M.; Mizukami, T.; Suzuki, T. Identification of Jumonji AT-Rich Interactive Domain 1A inhibitors and their effect on cancer cells. ACS Med. Chem. Lett.,  2015, 6(6), 665-670.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00083] [PMID:  26101571] 
[228] 
King, O.N.F.; Li, X.S.; Sakurai, M.; Kawamura, A.; Rose, N.R.; Ng, S.S.S.; Quinn, A.M.; Rai, G.; Mott, B.T.; Beswick, P.; Klose, R.J.; Oppermann, U.; Jadhav, A.; Heightman, T.D.; Maloney, D.J.; Schofield, C.J.; Simeonov, A. Simeonov, Quantitative high-throughput screening identifies 8-hydroxyquinolines as cell-active histone demethylase inhibitors. PLoS One, 2010.
[http://dx.doi.org/10.1371/journal.pone.0015535] [PMID:  21124847] 
[229] 
Hopkinson, R.J.; Tumber, A.; Yapp, C.; Chowdhury, R.; Aik, W.; Che, K.H.; Li, X.S.; Kristensen, J.B.L.; King, O.N.F.; Chan, M.C.; Yeoh, K.K.; Choi, H.; Walport, L.J.; Thinnes, C.C.; Bush, J.T.; Lejeune, C.; Rydzik, A.M.; Rose, N.R.; Bagg, E.A.; McDonough, M.A.; Krojer, T.; Yue, W.W.; Ng, S.S.; Olsen, L.; Brennan, P.E.; Oppermann, U.; Muller-Knapp, S.; Klose, R.J.; Ratcliffe, P.J.; Schofield, C.J.; Kawamura, A. 5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation. Chem. Sci. (Camb.),  2013, 4(8), 3110-3117.
[http://dx.doi.org/10.1039/c3sc51122g] [PMID:  26682036] 
[230] 
Thinnes, C.C.; England, K.S.; Kawamura, A.; Chowdhury, R.; Schofield, C.J.; Hopkinson, R.J. Targeting histone lysine demethylases - progress, challenges, and the future. Biochim. Biophys. Acta,  2014, 1839(12), 1416-1432.
[http://dx.doi.org/10.1016/j.bbagrm.2014.05.009] [PMID:  24859458] 
[231] 
Mackeen, M.M.; Kramer, H.B.; Chang, K-H.; Coleman, M.L.; Hopkinson, R.J.; Schofield, C.J.; Kessler, B.M. Small-molecule-based inhibition of histone demethylation in cells assessed by quantitative mass spectrometry. J. Proteome Res.,  2010, 9(8), 4082-4092.
[http://dx.doi.org/10.1021/pr100269b] [PMID:  20583823] 
[232] 
Thalhammer, A.; Mecinović, J.; Loenarz, C.; Tumber, A.; Rose, N.R.; Heightman, T.D.; Schofield, C.J. Inhibition of the histone demethylase JMJD2E by 3-substituted pyridine 2,4-dicarboxylates. Org. Biomol. Chem.,  2011, 9(1), 127-135.
[http://dx.doi.org/10.1039/C0OB00592D] [PMID:  21076780] 
[233] 
Wang, L.; Chang, J.; Varghese, D.; Dellinger, M.; Kumar, S.; Best, A.M.; Ruiz, J.; Bruick, R.; Peña-Llopis, S.; Xu, J.; Babinski, D.J.; Frantz, D.E.; Brekken, R.A.; Quinn, A.M.; Simeonov, A.; Easmon, J.; Martinez, E.D. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat. Commun.,  2013, 4, 2035.
[http://dx.doi.org/10.1038/ncomms3035] [PMID:  23792809] 
[234] 
McAllister, T.E.; England, K.S.; Hopkinson, R.J.; Brennan, P.E.; Kawamura, A.; Schofield, C.J. Recent Progress in Histone Demethylase Inhibitors. J. Med. Chem.,  2016, 59(4), 1308-1329.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01758] [PMID:  26710088] 
[235] 
Chang, K-H.; King, O.N.F.; Tumber, A.; Woon, E.C.Y.; Heightman, T.D.; McDonough, M.A.; Schofield, C.J.; Rose, N.R. Inhibition of histone demethylases by 4-carboxy-2,2′-bipyridyl compounds. ChemMedChem,  2011, 6(5), 759-764.
[http://dx.doi.org/10.1002/cmdc.201100026] [PMID:  21412984] 
[236] 
Welford, R.W.D.; Schlemminger, I.; McNeill, L.A.; Hewitson, K.S.; Schofield, C.J. The selectivity and inhibition of AlkB. J. Biol. Chem.,  2003, 278(12), 10157-10161.
[http://dx.doi.org/10.1074/jbc.M211058200] [PMID:  12517755] 
[237] 
Murray, J.C.; Cassell, R.H.; Pinnell, S.R. Inhibition of lysyl hydroxylase by catechol analogs. Biochim. Biophys. Acta,  1977, 481(1), 63-70.
[http://dx.doi.org/10.1016/0005-2744(77)90137-1] [PMID:  402945] 
[238] 
Wilson, W.J.; Poellinger, L. The dietary flavonoid quercetin modulates HIF-1 α activity in endothelial cells. Biochem. Biophys. Res. Commun.,  2002, 293(1), 446-450.
[http://dx.doi.org/10.1016/S0006-291X(02)00244-9] [PMID:  12054621] 
[239] 
Zhou, Y-D.; Kim, Y-P.; Li, X-C.; Baerson, S.R.; Agarwal, A.K.; Hodges, T.W.; Ferreira, D.; Nagle, D.G. Hypoxia-inducible factor-1 activation by (-)-epicatechin gallate: potential adverse effects of cancer chemoprevention with high-dose green tea extracts. J. Nat. Prod.,  2004, 67(12), 2063-2069.
[http://dx.doi.org/10.1021/np040140c] [PMID:  15620252] 
[240] 
Sakurai, M.; Rose, N.R.; Schultz, L.; Quinn, A.M.; Jadhav, A.; Ng, S.S.; Oppermann, U.; Schofield, C.J.; Simeonov, A. A miniaturized screen for inhibitors of Jumonji histone demethylases. Mol. Biosyst.,  2010, 6(2), 357-364.
[http://dx.doi.org/10.1039/B912993F] [PMID:  20094655] 
[241] 
Nielsen, A.L.; Kristensen, L.H.; Stephansen, K.B.; Kristensen, J.B.L.; Helgstrand, C.; Lees, M.; Cloos, P.; Helin, K.; Gajhede, M.; Olsen, L. Identification of catechols as histone-lysine demethylase inhibitors. FEBS Lett.,  2012, 586(8), 1190-1194.
[http://dx.doi.org/10.1016/j.febslet.2012.03.001] [PMID:  22575654] 
[242] 
Kruidenier, L.; Chung, C.; Cheng, Z.; Liddle, J.; Che, K.H.; Joberty, G.; Bantscheff, M.; Bountra, C.; Bridges, A.; Diallo, H.; Eberhard, D.; Hutchinson, S.; Jones, E.; Katso, R.; Leveridge, M.; Mander, P.K.; Mosley, J.; Ramirez-Molina, C.; Rowland, P.; Schofield, C.J.; Sheppard, R.J.; Smith, J.E.; Swales, C.; Tanner, R.; Thomas, P.; Tumber, A.; Drewes, G.; Oppermann, U.; Patel, D.J.; Lee, K.; Wilson, D.M. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nat. Lond. UK.,  2012, 488(4711), 404-408.
[http://dx.doi.org/10.1038/nature11262] [PMID:  2284901] 
[243] 
Wissmann, M.; Yin, N.; Müller, J.M.; Greschik, H.; Fodor, B.D.; Jenuwein, T.; Vogler, C.; Schneider, R.; Günther, T.; Buettner, R.; Metzger, E.; Schüle, R. Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat. Cell Biol.,  2007, 9(3), 347-353.
[http://dx.doi.org/10.1038/ncb1546] [PMID:  17277772] 
[244] 
Rotili, D.; Tomassi, S.; Conte, M.; Benedetti, R.; Tortorici, M.; Ciossani, G.; Valente, S.; Marrocco, B.; Labella, D.; Novellino, E.; Mattevi, A.; Altucci, L.; Tumber, A.; Yapp, C.; King, O.N.F.; Hopkinson, R.J.; Kawamura, A.; Schofield, C.J.; Mai, A. Pan-histone demethylase inhibitors simultaneously targeting jumonji, c. pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities. J. Med. Chem.,  2014, 57(1), 42-55.
[http://dx.doi.org/10.1021/jm4012802] [PMID:  24325601] 
[245] 
Zhao, H.; Chen, T. Tet family of 5-methylcytosine dioxygenases in mammalian development. J. Hum. Genet.,  2013, 58(7), 421-427.
[http://dx.doi.org/10.1038/jhg.2013.63] [PMID:  23719188] 
[246] 
Pastor, W.A.; Aravind, L.; Rao, A. TETonic shift: biological roles of TET proteins in DNA demethylation and transcription. Nat. Rev. Mol. Cell Biol.,  2013, 14(6), 341-356.
[http://dx.doi.org/10.1038/nrm3589] [PMID:  23698584] 
[247] 
Branco, M.R.; Ficz, G.; Reik, W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat. Rev. Genet.,  2011, 13(1), 7-13.
[http://dx.doi.org/10.1038/nrg3080] [PMID:  22083101] 
[248] 
Williams, K.; Christensen, J.; Helin, K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep.,  2011, 13(1), 28-35.
[http://dx.doi.org/10.1038/embor.2011.233] [PMID:  22157888] 
[249] 
Ma, J-Y.; Zhang, T.; Shen, W.; Schatten, H.; Sun, Q.Y. Molecules and mechanisms controlling the active DNA demethylation of the mammalian zygotic genome. Protein Cell,  2014, 5(11), 827-836.
[http://dx.doi.org/10.1007/s13238-014-0095-3] [PMID:  25152302] 
[250] 
Scourzic, L.; Mouly, E.; Bernard, O.A. TET proteins and the control of cytosine demethylation in cancer. Genome Med.,  2015, 7(1), 9.
[http://dx.doi.org/10.1186/s13073-015-0134-6] [PMID:  25632305] 
[251] 
Kinney, S.R.M.; Pradhan, S. Ten eleven translocation enzymes and 5-hydroxymethylation in mammalian development and cancer. Adv. Exp. Med. Biol.,  2013, 754, 57-79.
[http://dx.doi.org/10.1007/978-1-4419-9967-2_3] [PMID:  22956496] 
[252] 
Guibert, S.; Weber, M. Functions of DNA methylation and hydroxymethylation in mammalian development. Curr. Top. Dev. Biol.,  2013, 104, 47-83.
[http://dx.doi.org/10.1016/B978-0-12-416027-9.00002-4] [PMID:  23587238] 
[253] 
Rasmussen, K.D.; Helin, K. Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev.,  2016, 30(7), 733-750.
[http://dx.doi.org/10.1101/gad.276568.115] [PMID:  27036965] 
[254] 
Dawlaty, M.M.; Breiling, A.; Le, T.; Barrasa, M.I.; Raddatz, G.; Gao, Q.; Powell, B.E.; Cheng, A.W.; Faull, K.F.; Lyko, F.; Jaenisch, R. Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev. Cell,  2014, 29(1), 102-111.
[http://dx.doi.org/10.1016/j.devcel.2014.03.003] [PMID:  24735881] 
[255] 
Gao, Y.; Chen, J.; Li, K.; Wu, T.; Huang, B.; Liu, W.; Kou, X.; Zhang, Y.; Huang, H.; Jiang, Y.; Yao, C.; Liu, X.; Lu, Z.; Xu, Z.; Kang, L.; Chen, J.; Wang, H.; Cai, T.; Gao, S. Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming. Cell Stem Cell,  2013, 12(4), 453-469.
[http://dx.doi.org/10.1016/j.stem.2013.02.005] [PMID:  23499384] 
[256] 
Kraus, T.F.J.; Greiner, A.; Steinmaurer, M.; Dietinger, V.; Guibourt, V.; Kretzschmar, H.A. Genetic characterization of ten-eleven-translocation methylcytosine dioxygenase alterations in human glioma. J. Cancer,  2015, 6(9), 832-842.
[http://dx.doi.org/10.7150/jca.12010] [PMID:  26284134] 
[257] 
Bassi, S.; Tripathi, T.; Monziani, A.; Di Leva, F.; Biagioli, M. Epigenetics of Huntington’s Disease. Adv. Exp. Med. Biol.,  2017, 978, 277-299.
[http://dx.doi.org/10.1007/978-3-319-53889-1_15] [PMID:  28523552] 
[258] 
Lardenoije, R.; Iatrou, A.; Kenis, G.; Kompotis, K.; Steinbusch, H.W.M.; Mastroeni, D.; Coleman, P.; Lemere, C.A.; Hof, P.R.; van den Hove, D.L.A.; Rutten, B.P.F. The epigenetics of aging and neurodegeneration. Prog. Neurobiol.,  2015, 131, 21-64.
[http://dx.doi.org/10.1016/j.pneurobio.2015.05.002] [PMID:  26072273] 
[259] 
Al-Mahdawi, S.; Virmouni, S.A.; Pook, M.A. The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases. Front. Neurosci.,  2014, 8, 397.
[http://dx.doi.org/10.3389/fnins.2014.00397] [PMID:  25538551] 
[260] 
Bradley-Whitman, M.A.; Lovell, M.A. Epigenetic changes in the progression of Alzheimer’s disease. Mech. Ageing Dev.,  2013, 134(10), 486-495.
[http://dx.doi.org/10.1016/j.mad.2013.08.005] [PMID:  24012631] 
[261] 
Coppieters, N.; Dieriks, B.V.; Lill, C.; Faull, R.L.M.; Curtis, M.A.; Dragunow, M. Global changes in DNA methylation and hydroxymethylation in Alzheimer’s disease human brain. Neurobiol. Aging,  2014, 35(6), 1334-1344.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.11.031] [PMID:  24387984] 
[262] 
Wang, F.; Yang, Y.; Lin, X.; Wang, J-Q.; Wu, Y-S.; Xie, W.; Wang, D.; Zhu, S.; Liao, Y-Q.; Sun, Q.; Yang, Y-G.; Luo, H-R.; Guo, C.; Han, C.; Tang, T-S. Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntington’s disease. Hum. Mol. Genet.,  2013, 22(18), 3641-3653.
[http://dx.doi.org/10.1093/hmg/ddt214] [PMID:  23669348] 
[263] 
Xu, X.; Tan, X.; Tampe, B.; Nyamsuren, G.; Liu, X.; Maier, L.S.; Sossalla, S.; Kalluri, R.; Zeisberg, M.; Hasenfuss, G.; Zeisberg, E.M. Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiac fibrosis. Cardiovasc. Res.,  2015, 105(3), 279-291.
[http://dx.doi.org/10.1093/cvr/cvv015] [PMID:  25616414] 
[264] 
Cull, A.H.; Snetsinger, B.; Buckstein, R.; Wells, R.A.; Rauh, M.J. Tet2 restrains inflammatory gene expression in macrophages. Exp. Hematol.,  2017, 55, 56-70.e13.
[http://dx.doi.org/10.1016/j.exphem.2017.08.001] [PMID:  28826859] 
[265] 
Peng, J.; Tang, Z-H.; Ren, Z.; He, B.; Zeng, Y.; Liu, L-S.; Wang, Z.; Wei, D-H.; Zheng, X-L.; Jiang, Z-S. TET2 Protects against oxLDL-Induced HUVEC Dysfunction by Upregulating the CSE/H2S System. Front. Pharmacol.,  2017, 8, 486.
[http://dx.doi.org/10.3389/fphar.2017.00486] [PMID:  28798687] 
[266] 
Bird, L. Inflammation: TET2: the terminator. Nat. Rev. Immunol.,  2015, 15(10), 598.
[http://dx.doi.org/10.1038/nri3912] [PMID:  26358395] 
[267] 
Fagone, P.; Mangano, K.; Di Marco, R.; Touil-Boukoffa, C.; Chikovan, T.; Signorelli, S.; Lombardo, G.A.G.; Patti, F.; Mammana, S.; Nicoletti, F. Expression of DNA methylation genes in secondary progressive multiple sclerosis. J. Neuroimmunol.,  2016, 290, 66-69.
[http://dx.doi.org/10.1016/j.jneuroim.2015.11.018] [PMID:  26711572] 
[268] 
Abdel-Hameed, E.A.; Ji, H.; Shata, M.T. HIV-induced epigenetic alterations in host cells. Adv. Exp. Med. Biol.,  2016, 879, 27-38.
[http://dx.doi.org/10.1007/978-3-319-24738-0_2] [PMID:  26659262] 
[269] 
Delatte, B.; Deplus, R.; Fuks, F. Playing TETris with DNA modifications. EMBO J.,  2014, 33(11), 1198-1211.
[http://dx.doi.org/10.15252/embj.201488290] [PMID:  24825349] 
[270] 
Hu, L.; Lu, J.; Cheng, J.; Rao, Q.; Li, Z.; Hou, H.; Lou, Z.; Zhang, L.; Li, W.; Gong, W.; Liu, M.; Sun, C.; Yin, X.; Li, J.; Tan, X.; Wang, P.; Wang, Y.; Fang, D.; Cui, Q.; Yang, P.; He, C.; Jiang, H.; Luo, C.; Xu, Y. Structural insight into substrate preference for TET-mediated oxidation. Nature,  2015, 527(7576), 118-122.
[http://dx.doi.org/10.1038/nature15713] [PMID:  26524525] 
[271] 
Bassan, A.; Blomberg, M.R.A.; Borowski, T.; Siegbahn, P.E.M. Theoretical studies of enzyme mechanisms involving high-valent iron intermediates. J. Inorg. Biochem.,  2006, 100(4), 727-743.
[http://dx.doi.org/10.1016/j.jinorgbio.2006.01.015] [PMID:  16513176] 
[272] 
Price, J.C.; Barr, E.W.; Hoffart, L.M.; Krebs, C.; Bollinger, J.M., Jr Kinetic dissection of the catalytic mechanism of taurine:α-ketoglutarate dioxygenase (TauD) from Escherichia coli. Biochemistry,  2005, 44(22), 8138-8147.
[http://dx.doi.org/10.1021/bi050227c] [PMID:  15924433] 
[273] 
Grzyska, P.K.; Appelman, E.H.; Hausinger, R.P.; Proshlyakov, D.A. Insight into the mechanism of an iron dioxygenase by resolution of steps following the FeIV=HO species. Proc. Natl. Acad. Sci. USA,  2010, 107(9), 3982-3987.
[http://dx.doi.org/10.1073/pnas.0911565107] [PMID:  20147623] 
[274] 
Liu, S.; Jiang, J.; Li, L.; Amato, N.J.; Wang, Z.; Wang, Y. Arsenite targets the zinc finger domains of tet proteins and inhibits tet-mediated oxidation of 5-Methylcytosine. Environ. Sci. Technol.,  2015, 49(19), 11923-11931.
[http://dx.doi.org/10.1021/acs.est.5b03386] [PMID:  26355596] 
[275] 
Alves, L.E.; Rose, E.P.; Cahill, T.B., Jr Intravenous amiodarone in the treatment of refractory arrhythmias. Crit. Care Med.,  1985, 13(9), 750-752.
[http://dx.doi.org/10.1097/00003246-198509000-00012] [PMID:  4028770] 
[276] 
Costa, Y.; Ding, J.; Theunissen, T.W.; Faiola, F.; Hore, T.A.; Shliaha, P.V.; Fidalgo, M.; Saunders, A.; Lawrence, M.; Dietmann, S.; Das, S.; Levasseur, D.N.; Li, Z.; Xu, M.; Reik, W.; Silva, J.C.R.; Wang, J. NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature,  2013, 495(7441), 370-374.
[http://dx.doi.org/10.1038/nature11925] [PMID:  23395962] 
[277] 
Wang, Y.; Xiao, M.; Chen, X.; Chen, L.; Xu, Y.; Lv, L.; Wang, P.; Yang, H.; Ma, S.; Lin, H.; Jiao, B.; Ren, R.; Ye, D.; Guan, K-L.; Xiong, Y. WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol. Cell,  2015, 57(4), 662-673.
[http://dx.doi.org/10.1016/j.molcel.2014.12.023] [PMID:  25601757] 
[278] 
Cartron, P-F.; Nadaradjane, A.; Lepape, F.; Lalier, L.; Gardie, B.; Vallette, F.M. Identification of TET1 partners that control its DNA-Demethylating function. Genes Cancer,  2013, 4(5-6), 235-241.
[http://dx.doi.org/10.1177/1947601913489020] [PMID:  24069510] 
[279] 
Cheray, M.; Pacaud, R.; Nadaradjane, A.; Oliver, L.; Vallette, F.M.; Cartron, P-F. Specific inhibition of dnmt3a/isgf3γ interaction increases the temozolomide efficiency to reduce tumor growth. Theranostics,  2016, 6(11), 1988-1999.
[http://dx.doi.org/10.7150/thno.9150] [PMID:  27698935] 
[280] 
Cheray, M.; Pacaud, R.; Nadaradjane, A.; Vallette, F.M.; Cartron, P-F. Specific inhibition of one DNMT1-including complex influences tumor initiation and progression. Clin. Epigenetics,  2013, 5(1), 9.
[http://dx.doi.org/10.1186/1868-7083-5-9] [PMID:  23809695] 
[281] 
Cheray, M.; Nadaradjane, A.; Bonnet, P.; Routier, S.; Vallette, F.M.; Cartron, P-F. Specific inhibition of DNMT1/CFP1 reduces cancer phenotypes and enhances chemotherapy effectiveness. Epigenomics,  2014, 6(3), 267-275.
[http://dx.doi.org/10.2217/epi.14.18] [PMID:  25111481] 
[282] 
Ferrari-Amorotti, G.; Fragliasso, V.; Esteki, R.; Prudente, Z.; Soliera, A.R.; Cattelani, S.; Manzotti, G.; Grisendi, G.; Dominici, M.; Pieraccioli, M.; Raschellà, G.; Chiodoni, C.; Colombo, M.P.; Calabretta, B. Inhibiting interactions of lysine demethylase LSD1 with snail/slug blocks cancer cell invasion. Cancer Res.,  2013, 73(1), 235-245.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-1739] [PMID:  23054398] 
[283] 
Plummer, R.; Vidal, L.; Griffin, M.; Lesley, M.; de Bono, J.; Coulthard, S.; Sludden, J.; Siu, L.L.; Chen, E.X.; Oza, A.M.; Reid, G.K.; McLeod, A.R.; Besterman, J.M.; Lee, C.; Judson, I.; Calvert, H.; Boddy, A.V. Phase I study of MG98, an oligonucleotide antisense inhibitor of human DNA methyltransferase 1, given as a 7-day infusion in patients with advanced solid tumors. Clin. Cancer Res.,  2009, 15(9), 3177-3183.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2859] [PMID:  19383817] 
[284] 
Yamamoto, H.A.; Mohanan, P.V. Effect of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA damage and seizures induced by kainic acid in mice. Toxicol. Lett.,  2003, 143(2), 115-122.
[http://dx.doi.org/10.1016/S0378-4274(03)00114-0] [PMID:  12749815] 
[285] 
Xu, W.; Yang, H.; Liu, Y.; Yang, Y.; Wang, P.; Kim, S-H.; Ito, S.; Yang, C.; Wang, P.; Xiao, M-T.; Liu, L.X.; Jiang, W.Q.; Liu, J.; Zhang, J.Y.; Wang, B.; Frye, S.; Zhang, Y.; Xu, Y.H.; Lei, Q.Y.; Guan, K-L.; Zhao, S.M.; Xiong, Y. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell,  2011, 19(1), 17-30.
[http://dx.doi.org/10.1016/j.ccr.2010.12.014] [PMID:  21251613] 
[286] 
Ko, M.; An, J.; Bandukwala, H.S.; Chavez, L.; Aijö, T.; Pastor, W.A.; Segal, M.F.; Li, H.; Koh, K.P.; Lähdesmäki, H.; Hogan, P.G.; Aravind, L.; Rao, A. Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX. Nature,  2013, 497(7447), 122-126.
[http://dx.doi.org/10.1038/nature12052] [PMID:  23563267] 
[287] 
Cimmino, L.; Dolgalev, I.; Wang, Y.; Yoshimi, A.; Martin, G.H.; Wang, J.; Ng, V.; Xia, B.; Witkowski, M.T.; Mitchell-Flack, M.; Grillo, I.; Bakogianni, S.; Ndiaye-Lobry, D.; Martín, M.T.; Guillamot, M.; Banh, R.S.; Xu, M.; Figueroa, M.E.; Dickins, R.A.; Abdel-Wahab, O.; Park, C.Y.; Tsirigos, A.; Neel, B.G.; Aifantis, I. Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression. Cell,  2017, 170(6), 1079-1095.e20.
[http://dx.doi.org/10.1016/j.cell.2017.07.032] [PMID:  28823558] 
[288] 
Martinet, N.; Bertrand, P. Interpreting clinical assays for histone deacetylase inhibitors. Cancer Manag. Res.,  2011, 3, 117-141.
[http://dx.doi.org/10.2147/CMR.S9661] [PMID:  21625397] 
[289] 
Maeda, H. Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity. Adv. Drug Deliv. Rev.,  2015, 91, 3-6.
[http://dx.doi.org/10.1016/j.addr.2015.01.002] [PMID:  25579058] 
[290] 
Allen, T.M.; Martin, F.J. Advantages of liposomal delivery systems for anthracyclines. Semin. Oncol.,  2004, 31(6)(Suppl. 13), 5-15.
[http://dx.doi.org/10.1053/j.seminoncol.2004.08.001] [PMID:  15717735] 
[291] 
Gabizon, A.; Shmeeda, H.; Barenholz, Y. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin. Pharmacokinet.,  2003, 42(5), 419-436.
[http://dx.doi.org/10.2165/00003088-200342050-00002] [PMID:  12739982] 
[292] 
el Bahhaj, F.; Dekker, F.J.; Martinet, N.; Bertrand, P. Delivery of epidrugs. Drug Discov. Today,  2014, 19(9), 1337-1352.
[http://dx.doi.org/10.1016/j.drudis.2014.03.017] [PMID:  24680930] 
[293] 
Delatouche, R.; Denis, I.; Grinda, M.; El Bahhaj, F.; Baucher, E.; Collette, F.; Héroguez, V.; Grégoire, M.; Blanquart, C.; Bertrand, P. Design of pH responsive clickable prodrugs applied to histone deacetylase inhibitors: a new strategy for anticancer therapy. Eur. J. Pharm. Biopharm.,  2013, 85(3 Pt B), 862-872.
[http://dx.doi.org/10.1016/j.ejpb.2013.03.006] [PMID:  23537575] 
[294] 
Gueugnon, F.; Denis, I.; Pouliquen, D.; Collette, F.; Delatouche, R.; Héroguez, V.; Grégoire, M.; Bertrand, P.; Blanquart, C. Nanoparticles produced by ring-opening metathesis polymerization using norbornenyl-poly (ethylene oxide) as a ligand-free generic platform for highly selective in vivo tumor targeting. Biomacromolecules,  2013, 14(7), 2396-2402.
[http://dx.doi.org/10.1021/bm400516b] [PMID:  23731363] 
[295] 
Charrier, C.; Clarhaut, J.; Gesson, J-P.; Estiu, G.; Wiest, O.; Roche, J.; Bertrand, P. Synthesis and modeling of new benzofuranone histone deacetylase inhibitors that stimulate tumor suppressor gene expression. J. Med. Chem.,  2009, 52(9), 3112-3115.
[http://dx.doi.org/10.1021/jm9002439] [PMID:  19385600] 
[296] 
El Bahhaj, F.; Denis, I.; Pichavant, L.; Delatouche, R.; Collette, F.; Linot, C.; Pouliquen, D.; Grégoire, M.; Héroguez, V.; Blanquart, C.; Bertrand, P. Histone Deacetylase Inhibitors Delivery using Nanoparticles with Intrinsic Passive Tumor Targeting Properties for Tumor Therapy. Theranostics,  2016, 6(6), 795-807.
[http://dx.doi.org/10.7150/thno.13725] [PMID:  27162550] 
[297] 
Baylin, S.B.; Jones, P.A. A decade of exploring the cancer epigenome - biological and translational implications. Nat. Rev. Cancer,  2011, 11(10), 726-734.
[http://dx.doi.org/10.1038/nrc3130] [PMID:  21941284] 
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DOI https://dx.doi.org/10.2174/0929867325666180706105903	Print ISSN 0929-8673
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Current Medicinal Chemistry

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