Histone deacetylase inhibitors as therapeutics for endometriosis

Expert Review of Obstetrics and Gynecology

Volumn 7, Issue 5, 2012, Pages 451-466

  Li, Xin ^a   Liu, Xishi ^a   Guo, Sun Wei ^a  

^a FUDAN UNIVERSITY   (China)

Author keywords

clinical trial; drug research and development; endometriosis; histone deacetylase inhibitor; valproic acid

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ANGIOGENESIS INHIBITOR; ANTIINFLAMMATORY AGENT; APICIDIN; AZACITIDINE; DANAZOL; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; GESTAGEN; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROGESTERONE; ROMIDEPSIN; STEROIDOGENIC FACTOR 1; TRICHOSTATIN A; VALPROIC ACID; VORINOSTAT;

ADENOMYOSIS; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CHROMOSOME ABERRATION; DNA METHYLATION; DNMT1 GENE; DNMT3A GENE; DNMT3B GENE; DRUG COST; DRUG EFFICACY; DRUG RESEARCH; DRUG SAFETY; DYSMENORRHEA; ENDOMETRIOSIS; ENZYME INHIBITION; EPIGENETICS; EPILEPSY; FEMALE INFERTILITY; FINANCIAL MANAGEMENT; GENE; GENE EXPRESSION; GENETIC DISORDER; HISTONE MODIFICATION; HOXA10 GENE; HUMAN; MYELODYSPLASTIC SYNDROME; NEUROPATHIC PAIN; NONHUMAN; PELVIS PAIN SYNDROME; PHARMACOGENETICS; PR B GENE; PROMOTER REGION; REVIEW; STEROIDOGENIC FACTOR 1 GENE; TERATOGENICITY; UTERUS CONTRACTILITY;

EID: 84867552662     PISSN: 17474108     EISSN: 17474116     Source Type: Journal    
DOI: 10.1586/eog.12.52     Document Type: Review

References (145)

1. Giudice LC, Kao LC. Endometriosis. Lancet 364(9447), 1789-1799 (2004).
2. Farquhar CM. Extracts from the 'clinical evidence'. Endometriosis. BMJ 320(7247), 1449-1452 (2000).
3. Boling RO, Abbasi R, Ackerman G, Schipul AH Jr, Chaney SA. Disability from endometriosis in the United States Army. J. Reprod. Med. 33(1), 49-52 (1988).
4. Kjerulff KH, Erickson BA, Langenberg PW. Chronic gynecological conditions reported by US women: Findings from the National Health Interview Survey, 1984 to 1992. Am. J. Public Health 86(2), 195-199 (1996).
5. Waller KG, Shaw RW. Gonadotropinreleasing hormone analogues for the treatment of endometriosis: Long-term follow-up. Fertil. Steril. 59(3), 511-515 (1993).
6. Kiilholma P, Tuimala R, Kivinen S, Korhonen M, Hagman E. Comparison of the gonadotropin-releasing hormone agonist goserelin acetate alone versus goserelin combined with estrogen-progestogen add-back therapy in the treatment of endometriosis. Fertil. Steril. 64(5), 903-908 (1995).
7. Lessey BA. Medical management of endometriosis and infertility. Fertil. Steril. 73(6), 1089-1096 (2000).
8. Bulun SE, Lin Z, Imir G et al. Regulation of aromatase expression in estrogenresponsive breast and uterine disease: From bench to treatment. Pharmacol. Rev. 57(3), 359-383 (2005).
9. Kennedy S, Bergqvist A, Chapron C et al.; ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Development Group. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum. Reprod. 20(10), 2698-2704 (2005).
10. Nothnick WB, D'Hooghe TM. Medical management of endometriosis: novel targets and approaches towards the development of future treatment regimes. Gynecol. Obstet. Invest. 55(4), 189-198 (2003).
11. Fedele L, Berlanda N. Emerging drugs for endometriosis. Expert Opin. Emerg. Drugs 9(1), 167-177 (2004).
12. Guo SW, Hummelshoj L, Olive DL, Bulun SE, D'Hooghe TM, Evers JL. A call for more transparency of registered clinical trials on endometriosis. Hum. Reprod. 24(6), 1247-1254 (2009).
13. Vercellini P, Crosignani P, Somigliana E, Viganó P, Frattaruolo MP, Fedele L.'Waiting for Godot': A commonsense approach to the medical treatment of endometriosis. Hum. Reprod. 26(1), 3-13 (2011).
14. Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW. Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am. J. Obstet. Gynecol. 193(2), 371-380 (2005).
15. Troiano RN, Taylor KJ. Sonographically guided therapeutic aspiration of benignappearing ovarian cysts and endometriomas. AJR. Am. J. Roentgenol. 171(6), 1601-1605 (1998).
16. Taylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J. Clin. Invest. 101(7), 1379-1384 (1998).
17. Taylor HS, Bagot C, Kardana A, Olive D, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum. Reprod. 14(5), 1328-1331 (1999).
18. Gui Y, Zhang J, Yuan L, Lessey BA. Regulation of HOXA-10 and its expression in normal and abnormal endometrium. Mol. Hum. Reprod. 5(9), 866-873 (1999).
19. Szczepanska M, Wirstlein P, Luczak M, Jagodzinski PP, Skrzypczak J. Reduced expression of HOXA10 in the midluteal endometrium from infertile women with minimal endometriosis. Biomed. Pharmacother. 64(10), 697-705 (2010).
20. Kim JJ, Taylor HS, Lu Z et al. Altered expression of HOXA10 in endometriosis: Potential role in decidualization. Mol. Hum. Reprod. 13(5), 323-332 (2007).
21. Lee B, Du H, Taylor HS. Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol. Reprod. 80(1), 79-85 (2009).
22. Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis. Epigenetics 1(2), 106-111 (2006).
23. Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but not B is expressed in endometriosis. J. Clin. Endocrinol. Metab. 85(8), 2897-2902 (2000).
24. Jichan N, Xishi L, Guo SW. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in adenomyosis and its rectification by a histone deacetylase inhibitor and a demethylation agent. Reprod. Sci. 17(11), 995-1005 (2010).
25. Bromer JG, Wu J, Zhou Y, Taylor HS. Hypermethylation of homeobox A10 by in utero diethylstilbestrol exposure: An epigenetic mechanism for altered developmental programming. Endocrinology 150(7), 3376-3382 (2009).
26. Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertil. Steril. 87(1), 24-32 (2007).
27. van Kaam KJ, Delvoux B, Romano A, D'Hooghe T, Dunselman GA, Groothuis PG. Deoxyribonucleic acid methyltransferases and methyl-CpGbinding domain proteins in human endometrium and endometriosis. Fertil. Steril. 95(4), 1421-1427 (2011).
28. Szczepanska M, Wirstlein P, Skrzypczak J, Jagodzinski PP. Expression of HOXA11 in the mid-luteal endometrium from women with endometriosis-associated infertility. Reprod. Biol. Endocrinol. 10, 1 (2012).
29. Sun L, Zhao H, Xu Z et al. Phosphatidylinositol 3-kinase/protein kinase B pathway stabilizes DNA methyltransferase I protein and maintains DNA methylation. Cell. Signal. 19(11), 2255-2263 (2007).
30. Liu XS, Guo SW. Aberrant immunoreactivity of deoxyribonucleic acid methyltransferases (DNMTs) in adenomyosis. Gynecol. Obstet. Invest. doi:10.1159/000337718 (2012) (Epub ahead of print).
31. Xue Q, Lin Z, Yin P et al. Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5′ CpG island in endometriosis. J. Clin. Endocrinol. Metab. 92(8), 3261-3267 (2007).
32. Xue Q, Lin Z, Cheng YH et al. Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol. Reprod. 77(4), 681-687 (2007).
33. Izawa M, Harada T, Taniguchi F, Ohama Y, Takenaka Y, Terakawa N. An epigenetic disorder may cause aberrant expression of aromatase gene in endometriotic stromal cells. Fertil. Steril. 89(Suppl. 5), 1390-1396 (2008).
34. Izawa M, Taniguchi F, Uegaki T et al. Demethylation of a nonpromoter cytosine-phosphate-guanine island in the aromatase gene may cause the aberrant up-regulation in endometriotic tissues. Fertil. Steril. 95(1), 33-39 (2011).
35. Starzinski-Powitz A, Gaetje R, Zeitvogel A et al. Tracing cellular and molecular mechanisms involved in endometriosis. Hum. Reprod. Update 4(5), 724-729 (1998).
36. Starzinski-Powitz A, Zeitvogel A, Schreiner A, Baumann R. In search of pathogenic mechanisms in endometriosis: The challenge for molecular cell biology. Curr. Mol. Med. 1(6), 655-664 (2001).
37. Wu Y, Starzinski-Powitz A, Guo SW. Trichostatin A, a histone deacetylase inhibitor, attenuates invasiveness and reactivates E-cadherin expression in immortalized endometriotic cells. Reprod. Sci. 14(4), 374-382 (2007).
38. Wren JD, Wu Y, Guo SW. A system-wide analysis of differentially expressed genes in ectopic and eutopic endometrium. Hum. Reprod. 22(8), 2093-2102 (2007).
39. Borghese B, Barbaux S, Mondon F et al. Research resource: genome-wide profiling of methylated promoters in endometriosis reveals a subtelomeric location of hypermethylation. Mol. Endocrinol. 24(9), 1872-1885 (2010).
40. Zelenko Z, Aghajanova L, Irwin JC, Giudice LC. Nuclear receptor, coregulator signaling, and chromatin remodeling pathways suggest involvement of the epigenome in the steroid hormone response of endometrium and abnormalities in endometriosis. Reprod. Sci. 19(2), 152-162 (2012).
41. Kawano Y, Nasu K, Li H et al. Application of the histone deacetylase inhibitors for the treatment of endometriosis: Histone modifications as pathogenesis and novel therapeutic target. Hum. Reprod. 26(9), 2486-2498 (2011).
42. Colón-Díaz M., Báez-Vega P., García M et al. HDAC1 and HDAC2 are differentially expressed in endometriosis. Reprod. Sci. 19(5), 483-492 (2012).
43. Liu X, Nie J, Guo SW. Elevated immunoreactivity against class I histone deacetylases (HDACs) in adenomyosis. Gynecol. Obstet. Invest. 74, 50-55 (2012).
44. Guo SW. The endometrial epigenome and its response to steroid hormones. Mol. Cell. Endocrinol. 358(2), 185-196 (2012).
45. Fuks F. DNA methylation and histone modifications: Teaming up to silence genes. Curr. Opin. Genet. Dev. 15(5), 490-495 (2005).
46. Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat. Genet. 24(1), 88-91 (2000).
47. Silverman LR, Demakos EP, Peterson BL et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: A study of the cancer and leukemia group B. J. Clin. Oncol. 20(10), 2429-2440 (2002).
48. Kantarjian H, Issa JP, Rosenfeld CS et al. Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a Phase III randomized study. Cancer 106(8), 1794-1803 (2006).
49. Saiki JH, McCredie KB, Vietti TJ et al. 5-azacytidine in acute leukemia. Cancer 42(5), 2111-2114 (1978).
50. Guo SW. Emerging drugs for endometriosis. Expert Opin. Emerg. Drugs 13(4), 547-571 (2008).
51. Wu Y, Guo SW. Inhibition of proliferation of endometrial stromal cells by trichostatin A, RU486, CDB-2914, N-acetylcysteine, and ICI 182780. Gynecol. Obstet. Invest. 62(4), 193-205 (2006).
52. Wu Y, Guo SW. Histone deacetylase inhibitors trichostatin A and valproic acid induce cell cycle arrest and p21 expression in immortalized human endometrial stromal cells. Eur. J. Obstet. Gynecol. Reprod. Biol. 137(2), 198-203 (2008).
53. Wu Y, Starzinski-Powitz A, Guo SW. Constitutive and tumor necrosis factoralpha-stimulated activation of nuclear factor-kappaB in immortalized endometriotic cells and their suppression by trichostatin A. Gynecol. Obstet. Invest. 70(1), 23-33 (2010).
54. Imesch P, Fink D, Fedier A. Romidepsin reduces histone deacetylase activity, induces acetylation of histones, inhibits proliferation, and activates apoptosis in immortalized epithelial endometriotic cells. Fertil. Steril. 94(7), 2838-2842 (2010).
55. Ota H, Igarashi S, Sasaki M, Tanaka T. Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Hum. Reprod. 16(3), 561-566 (2001).
56. Matsuzaki S, Canis M, Pouly JL, Wattiez A, Okamura K, Mage G. Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium. Fertil. Steril. 82(5), 1309-1315 (2004).
57. Buchweitz O, Staebler A, Wüfing P, Hauzman E, Greb R, Kiesel L. COX-2 overexpression in peritoneal lesions is correlated with nonmenstrual chronic pelvic pain. Eur. J. Obstet. Gynecol. Reprod. Biol. 124(2), 216-221 (2006).
58. Yuan L, Shen F, Lu Y, Liu X, Guo SW. Cyclooxygenase-2 overexpression in ovarian endometriomas is associated with higher risk of recurrence. Fertil. Steril. 91(4 Suppl.), 1303-1306 (2009).
59. Wu Y, Guo SW. Suppression of IL-1®-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells. Eur. J. Obstet. Gynecol. Reprod. Biol. 135(1), 88-93 (2007).
60. Peeters LL, Vigne JL, Tee MK, Zhao D, Waite LL, Taylor RN. PPAR γ represses VEGF expression in human endometrial cells: Implications for uterine angiogenesis. Angiogenesis 8(4), 373-379 (2005).
61. Ohama Y, Harada T, Iwabe T, Taniguchi F, Takenaka Y, Terakawa N. Peroxisome proliferator-activated receptor-γ ligand reduced tumor necrosis factor-α-induced interleukin-8 production and growth in endometriotic stromal cells. Fertil. Steril. 89(2), 311-317 (2008).
62. Aytan H, Caliskan AC, Demirturk F, Aytan P, Koseoglu DR. Peroxisome proliferator-activated receptor-γ agonist rosiglitazone reduces the size of experimental endometriosis in the rat model. Aust. N. Z. J. Obstet. Gynaecol. 47(4), 321-325 (2007).
63. Lebovic DI, Kir M, Casey CL. Peroxisome proliferator-activated receptor-γ induces regression of endometrial explants in a rat model of endometriosis. Fertil. Steril. 82(Suppl. 3), 1008-1013 (2004).
64. Lebovic DI, Mwenda JM, Chai DC et al. PPAR-γ receptor ligand induces regression of endometrial explants in baboons: A prospective, randomized, placebo- and drug-controlled study. Fertil. Steril. 88(Suppl. 4), 1108-1119 (2007).
65. Wu Y, Guo SW. Peroxisome proliferatoractivated receptor-γ and retinoid X receptor agonists synergistically suppress proliferation of immortalized endometrial stromal cells. Fertil. Steril. 91(Suppl. 5), 2142-2147 (2009).
66. Guo SW. Nuclear factor-κb (NF-κB): An unsuspected major culprit in the pathogenesis of endometriosis that is still at large? Gynecol. Obstet. Invest. 63(2), 71-97 (2007).
67. González-Ramos R, Donnez J, Defrère S et al. Nuclear factor-|B is constitutively activated in peritoneal endometriosis. Mol. Hum. Reprod. 13(7), 503-509 (2007).
68. Gonzalez-Ramos R, Van Langendonckt A, Defrere S et al. Involvement of the nuclear factor-|B pathway in the pathogenesis of endometriosis. Fertil. Steril. 94(6), 1985-1994 (2010).
69. Imesch P, Samartzis EP, Schneider M, Fink D, Fedier A. Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin. Fertil. Steril. 95(5), 1579-1583 (2011).
70. Wang B, Xiao Y, Ding BB et al. Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 4(1), 19-29 (2003).
71. Shen F, Liu X, Geng JG, Guo SW. Increased immunoreactivity to SLIT/ROBO1 in ovarian endometriomas: A likely constituent biomarker for recurrence. Am. J. Pathol. 175(2), 479-488 (2009).
72. Guo SW, Zheng Y, Lu Y, Liu XS, Geng JG. Slit2 overexpression results in increased microvessel density and lesion size in mice with induced endometriosis. Reprod. Sci. 19, 1A-70A (2012).
73. Bulletti C, DE Ziegler D, Setti PL, Cicinelli E, Polli V, Flamigni C. The patterns of uterine contractility in normal menstruating women: From physiology to pathology. Ann. N. Y. Acad. Sci. 1034, 64-83 (2004).
74. Kitlas A, Oczeretko E, Swiatecka J, Borowska M, Laudanski T. Uterine contraction signals-application of the linear synchronization measures. Eur. J. Obstet. Gynecol. Reprod. Biol. 144(Suppl. 1), S61-S64 (2009).
75. Moynihan AT, Hehir MP, Sharkey AM, Robson SC, Europe-Finner GN, Morrison JJ. Histone deacetylase inhibitors and a functional potent inhibitory effect on human uterine contractility. Am. J. Obstet. Gynecol. 199(2), 167.e1-167.e7 (2008).
76. Ruddock NK, Shi SQ, Jain S et al. Progesterone, but not 17-α-hydroxyprogesterone caproate, inhibits human myometrial contractions. Am. J. Obstet. Gynecol. 199(4), 391.e1-391.e7 (2008).
77. Johannessen CU, Johannessen SI. Valproate: Past, present, and future. CNS Drug Rev. 9(2), 199-216 (2003).
78. Spina E, Perugi G. Antiepileptic drugs: Indications other than epilepsy. Epileptic Disord. 6(2), 57-75 (2004).
79. Kochar DK, Jain N, Agarwal RP, Srivastava T, Agarwal P, Gupta S. Sodium valproate in the management of painful neuropathy in Type 2 diabetes-a randomized placebo controlled study. Acta Neurol. Scand. 106(5), 248-252 (2002).
80. Kochar DK, Rawat N, Agrawal RP et al. Sodium valproate for painful diabetic neuropathy: A randomized double-blind placebo-controlled study. QJM 97(1), 33-38 (2004).
81. Winkler I, Blotnik S, Shimshoni J, Yagen B, Devor M, Bialer M. Efficacy of antiepileptic isomers of valproic acid and valpromide in a rat model of neuropathic pain. Br. J. Pharmacol. 146(2), 198-208 (2005).
82. Chiechio S, Zammataro M, Morales ME et al. Epigenetic modulation of mGlu2 receptors by histone deacetylase inhibitors in the treatment of inflammatory pain. Mol. Pharmacol. 75(5), 1014-1020 (2009).
83. Zhang Z, Cai YQ, Zou F, Bie B, Pan ZZ. Epigenetic suppression of GAD65 expression mediates persistent pain. Nat. Med. 17(11), 1448-1455 (2011).
84. Basselin M, Chang L, Chen M, Bell JM, Rapoport SI. Chronic administration of valproic acid reduces brain NMDA signaling via arachidonic acid in unanesthetized rats. Neurochem. Res. 33(11), 2229-2240 (2008).
85. Rahnama F, Thompson B, Steiner M, Shafiei F, Lobie PE, Mitchell MD. Epigenetic regulation of E-cadherin controls endometrial receptivity. Endocrinology 150(3), 1466-1472 (2009).
86. Logan PC, Ponnampalam AP, Rahnama F, Lobie PE, Mitchell MD. The effect of DNA methylation inhibitor 5-aza-2′-deoxycytidine on human endometrial stromal cells. Hum. Reprod. 25(11), 2859-2869 (2010).
87. Sakai N, Maruyama T, Sakurai R et al. Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells. J. Biol. Chem. 278(19), 16675-16682 (2003).
88. Uchida H, Maruyama T, Nagashima T, Asada H, Yoshimura Y. Histone deacetylase inhibitors induce differentiation of human endometrial adenocarcinoma cells through up-regulation of glycodelin. Endocrinology 146(12), 5365-5373 (2005).
89. Uchida H, Maruyama T, Ono M et al. Histone deacetylase inhibitors stimulate cell migration in human endometrial adenocarcinoma cells through up-regulation of glycodelin. Endocrinology 148(2), 896-902 (2007).
90. Uchida H, Maruyama T, Ohta K et al. Histone deacetylase inhibitor-induced glycodelin enhances the initial step of implantation. Hum. Reprod. 22(10), 2615-2622 (2007).
91. Lu Y, Nie J, Liu X, Zheng Y, Guo SW. Trichostatin A, a histone deacetylase inhibitor, reduces lesion growth and hyperalgesia in experimentally induced endometriosis in mice. Hum. Reprod. 25(4), 1014-1025 (2010).
92. Liu M, Liu X, Zhang Y, Guo SW. Valproic acid and progestin inhibit lesion growth and reduce hyperalgesia in experimentally induced endometriosis in rats. Reprod. Sci. 19(4), 360-373 (2012).
93. Liu X, Guo SW. A pilot study on the off-label use of valproic acid to treat adenomyosis. Fertil. Steril. 89(1), 246-250 (2008).
94. Liu X, Yuan L, Guo SW. Valproic acid as a therapy for adenomyosis: A comparative case series. Reprod. Sci. 17(10), 904-912 (2010).
95. Mao X, Wang Y, Carter AV, Zhen X, Guo SW. The retardation of myometrial infiltration, reduction of uterine contractility, and alleviation of generalized hyperalgesia in mice with induced adenomyosis by levo-tetrahydropalmatine (l-THP) and andrographolide. Reprod. Sci. 18(10), 1025-1037 (2011).
96. Liu X, Guo SW. Valproic acid alleviates generalized hyperalgesia in mice with induced adenomyosis. J. Obstet. Gynaecol. Res. 37(7), 696-708 (2011).
97. Zhao T, Liu X, Zhen X, Guo SW. Levo-tetrahydropalmatine retards the growth of ectopic endometrial implants and alleviates generalized hyperalgesia in experimentally induced endometriosis in rats. Reprod. Sci. 18(1), 28-45 (2011).
98. Gao YJ, Ji RR. c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury? Open Pain J. 2, 11-17 (2009).
99. Latremoliere A, Woolf CJ. Central sensitization: A generator of pain hypersensitivity by central neural plasticity. J. Pain 10(9), 895-926 (2009).
100. Ikeuchi M, Kolker SJ, Burnes LA, Walder RY, Sluka KA. Role of ASIC3 in the primary and secondary hyperalgesia produced by joint inflammation in mice. Pain 137(3), 662-669 (2008).
101. Taubøll E, Gregoraszczuk EL, Wojtowicz AK, Milewicz T. Effects of levetiracetam and valproate on reproductive endocrine function studied in human ovarian follicular cells. Epilepsia 50(8), 1868-1874 (2009).
102. von Krogh K, Harjen H, Almås C et al. The effect of valproate and levetiracetam on steroidogenesis in forskolin-stimulated H295R cells. Epilepsia 51(11), 2280-2288 (2010).
103. Lindström TM, Mohan AR, Johnson MR, Bennett PR. Histone deacetylase inhibitors exert time-dependent effects on nuclear factor-κB but consistently suppress the expression of proinflammatory genes in human myometrial cells. Mol. Pharmacol. 74(1), 109-121 (2008).
104. Wang J, Mahmud SA, Bitterman PB, Huo Y, Slungaard A. Histone deacetylase inhibitors suppress TF-κB-dependent agonist-driven tissue factor expression in endothelial cells and monocytes. J. Biol. Chem. 282(39), 28408-28418 (2007).
105. Dong XF, Song Q, Li LZ, Zhao CL, Wang LQ. Histone deacetylase inhibitor valproic acid inhibits proliferation and induces apoptosis in KM3 cells via downregulating VEGF receptor. Neuro Endocrinol. Lett. 28(6), 775-780 (2007).
106. Krikun G, Hu Z, Osteen K et al. The immunoconjugate 'icon' targets aberrantly expressed endothelial tissue factor causing regression of endometriosis. Am. J. Pathol. 176(2), 1050-1056 (2010).
107. Krikun G, Schatz F, Taylor H, Lockwood CJ. Endometriosis and tissue factor. Ann. N. Y. Acad. Sci. 1127, 101-105 (2008).
108. Rogers PA, Donoghue JF, Walter LM, Girling JE. Endometrial angiogenesis, vascular maturation, and lymphangiogenesis. Reprod. Sci. 16(2), 147-151 (2009).
109. Cameron EE, Bachman KE, Myöhänen S, Herman JG, Baylin SB. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. 21(1), 103-107 (1999).
110. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil. Steril. 68(4), 585-596 (1997).
111. Wu Y, Kajdacsy-Balla A, Strawn E et al. Transcriptional characterizations of differences between eutopic and ectopic endometrium. Endocrinology 147(1), 232-246 (2006).
112. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300(5618), 455 (2003).
113. Gaudet F, Hodgson JG, Eden A et al. Induction of tumors in mice by genomic hypomethylation. Science 300(5618), 489-492 (2003).
114. Suzuki H, Gabrielson E, Chen W et al. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat. Genet. 31(2), 141-149 (2002).
115. Heller G, Schmidt WM, Ziegler B et al. Genome-wide transcriptional response to 5-aza-2′-deoxycytidine and trichostatin A in multiple myeloma cells. Cancer Res. 68(1), 44-54 (2008).
116. Liang G, Gonzales FA, Jones PA, Orntoft TF, Thykjaer T. Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2′-deoxycytidine. Cancer Res. 62(4), 961-966 (2002).
117. Van Lint C, Emiliani S, Verdin E. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr. 5(4-5), 245-253 (1996).
118. Ornoy A. Valproic acid in pregnancy: How much are we endangering the embryo and fetus? Reprod. Toxicol. 28(1), 1-10 (2009).
119. Detich N, Bovenzi V, Szyf M. Valproate induces replication-independent active DNA demethylation. J. Biol. Chem. 278(30), 27586-27592 (2003).
120. Milutinovic S, D'Alessio AC, Detich N, Szyf M. Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. Carcinogenesis 28(3), 560-571 (2007).
121. Dong E, Chen Y, Gavin DP, Grayson DR, Guidotti A. Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. Epigenetics 5(8), 730-735 (2010).
122. Felisbino MB, Tamashiro WM, Mello ML. Chromatin remodeling, cell proliferation and cell death in valproic acid-treated HeLa cells. PLoS ONE 6(12), e29144 (2011).
123. Bodden-Heidrich R, Hilberink M, Frommer J et al. Qualitative research on psychosomatic aspects of endometriosis. Z. Psychosom. Med. Psychother. 45(4), 372-389 (1999).
124. Yang AS, Estecio MR, Garcia-Manero G, Kantarjian HM, Issa JP. Comment on 'Chromosomal instability and tumors promoted by DNA hypomethylation' and 'Induction of tumors in nice by genomic hypomethylation'. Science 302(5648), 1153; author reply 1153 (2003).
125. Lübert M, Wijermans P, Kunzmann R et al. Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br. J. Haematol. 114(2), 349-357 (2001).
126. Garcia-Manero M, Santana GT, Alcázar JL. Relationship between microvascular density and expression of vascular endothelial growth factor in patients with ovarian endometriosis. J. Womens. Health (Larchmt) 17(5), 777-782 (2008).
127. Watkins JR, Gough AW, McGuire EJ, Goldenthal E, de la Iglesia FA. Calcium valproate-induced uterine adenocarcinomas in Wistar rats. Toxicology 71(1-2), 35-47 (1992).
128. Hallas J, Friis S, Bjerrum L et al. Cancer risk in long-term users of valproate: A population-based case-control study. Cancer Epidemiol. Biomarkers Prev. 18(6), 1714-1719 (2009).
129. Chandrareddy A, Muneyyirci-Delale O. Risks versus benefits of valproic acid? Fertil. Steril. 90(1), 238; author reply 238-238; author reply 239 (2008).
130. Flük CE, Yaworsky DC, Miller WL. Effects of anticonvulsants on human p450c17 (17α-hydroxylase/17,20 lyase) and 3β-hydroxysteroid dehydrogenase type 2. Epilepsia 46(3), 444-448 (2005).
131. Bofinger DP, Feng L, Chi LH et al. Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of human endometrium. Toxicol. Sci. 62(2), 299-314 (2001).
132. McIntyre RS, Mancini DA, McCann S, Srinivasan J, Kennedy SH. Valproate, bipolar disorder and polycystic ovarian syndrome. Bipolar Disord. 5(1), 28-35 (2003).
133. Bahamondes L, Petta CA, Fernandes A, Monteiro I. Use of the levonorgestrelreleasing intrauterine system in women with endometriosis, chronic pelvic pain and dysmenorrhea. Contraception 75(6 Suppl.), S134-S139 (2007).
134. Zhang X, Yuan H, Deng L, Hu F, Ma J, Lin J. Evaluation of the efficacy of a danazol-loaded intrauterine contraceptive device on adenomyosis in an ICR mouse model. Hum. Reprod. 23(9), 2024-2030 (2008).
135. Kucharski R, Maleszka J, Foret S, Maleszka R. Nutritional control of reproductive status in honeybees via DNA methylation. Science 319(5871), 1827-1830 (2008).
136. Adams CP, Brantner VV. Estimating the cost of new drug development: Is it really 802 million dollars? Health Aff. (Millwood) 25(2), 420-428 (2006).
137. DiMasi JA, Hansen RW, Grabowski HG, Lasagna L. Cost of innovation in the pharmaceutical industry. J. Health Econ. 10(2), 107-142 (1991).
138. Carley DW. Drug repurposing: Identify, develop and commercialize new uses for existing or abandoned drugs. Part II. IDrugs 8(4), 310-313 (2005).
139. Carley DW. Drug repurposing: Identify, develop and commercialize new uses for existing or abandoned drugs. Part I. IDrugs 8(4), 306-309 (2005).
140. Toney JH, Fasick JI, Singh S, Beyrer C, Sullivan DJ Jr. Purposeful learning with drug repurposing. Science 325(5946), 1339-1340 (2009).
141. Ashburn TT, Thor KB. Drug repositioning: Identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov. 3(8), 673-683 (2004).
142. Oprea TI, Bauman JE, Bologa CG et al. Drug repurposing from an academic perspective. Drug Discov. Today Ther. Strateg. 8(3-4), 61-69 (2012).
143. Guo SW. Chapter 22: The epigenetics of endometriosis. In: Epigenetics in Human Disease. Tollefsbol T (Ed.). Elsevier and Academic Press, Amsterdam, The Netherlands (2012).
144. Suzuki A, Horiuchi A, Oka K, Miyamoto T, Kashima H, Shiozawa T. Immunohistochemical detection of steroid receptor cofactors in ovarian endometriosis: Involvement of down-regulated SRC-1 expression in the limited growth activity of the endometriotic epithelium. Virchows Arch. 456(4), 433-441 (2010).
145. Kumagami A, Ito A, Yoshida-Komiya H, Fujimori K, Sato A. Expression patterns of the steroid receptor coactivator family in human ovarian endometriosis. J. Obstet. Gynaecol. Res. 37(10), 1269-1276 (2011).