Role of epigenomics in ovarian and endometrial cancers

Epigenomics

Volumn 2, Issue 3, 2010, Pages 419-447

  Balch, Curtis ^a,b   Matei, Daniela E ^a,b   Huang, Tim H M ^c   Nephew, Kenneth P ^a,b  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b INDIANA UNIVERSITY   (United States)

^c OHIO STATE UNIVERSITY   (United States)

Author keywords

decitabine; DNA methylation; endometrial cancer; epigenetic biomarker; HDAC inhibitor; histone deacetylase; histone methylation; microRNA; ovarian cancer

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; 6 (1,3 DIOXO 1H,3H BENZO[DE]ISOQUINOLIN 2 YL) N HYDROXYHEXANAMIDE; ALPHA2B INTERFERON; APICIDIN; AZACITIDINE; BELINOSTAT; CARBOPLATIN; CISPLATIN; DNA METHYLTRANSFERASE INHIBITOR; GEMCITABINE; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; HYDRALAZINE; ISTODAX; M 344; MG 98; MICRORNA; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; NATURAL PRODUCT; OXAMFLATIN; PACLITAXEL; PLATINUM DERIVATIVE; PSAMMAPLIN A; PTEROSTILBENE; ROMIDEPSIN; SG 110; TAXANE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT; ZEBULARINE;

BLADDER CANCER; CANCER CHEMOTHERAPY; CANCER GRADING; CANCER STAGING; CANCER SURVIVAL; CHROMATIN; CHROMOSOME ABERRATION; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DNA METHYLATION; DNA REPAIR; DRUG APPROVAL; DRUG EFFICACY; DRUG SAFETY; ENDOMETRIUM CANCER; ENZYME INHIBITION; EPIGENETICS; FEMALE; FOOD AND DRUG ADMINISTRATION; GENE EXPRESSION; GENE MUTATION; GENOMICS; GYNECOLOGIC CANCER; HUMAN; LOW DRUG DOSE; MYELODYSPLASTIC SYNDROME; NONHUMAN; ONCOGENE; OVARY CANCER; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHENOTYPE; PRIORITY JOURNAL; PROGNOSIS; REVIEW; SKIN LYMPHOMA; SOLID TUMOR; T CELL LYMPHOMA; TREATMENT FAILURE; TREATMENT OUTCOME; TREATMENT RESPONSE;

DNA METHYLATION; DRUG RESISTANCE, NEOPLASM; ENDOMETRIAL NEOPLASMS; EPIGENOMICS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTONES; HUMANS; MICRORNAS; OVARIAN NEOPLASMS; TUMOR MARKERS, BIOLOGICAL;

EID: 77954125830     PISSN: 17501911     EISSN: 1750192X     Source Type: Journal    
DOI: 10.2217/epi.10.19     Document Type: Review

References (284)

1. 1975-2003 Cancer Of Status The On Nation The To Report Annual Et Al. La Ries X Wu H.Hl (2006). 1711-1742 8 107 Cancer Populations Hispanic/latino S. U. Among F.Cancer
2. Chiaffarino F, Pelucchi C, Parazzini F et al.: Reproductive and hormonal factors and ovarian cancer. Ann. Oncol. 12(3), 337-341 (2001).
3. Bosetti C, Negri E, Trichopoulos D et al.: Long-term effects of oral contraceptives on ovarian cancer risk. Int. J. Cancer 102(3), 262-265 (2002).
4. Jemal A, Siegel R, Ward E et al.: Cancer Statistics, 2008. CA Cancer J. Clin. 58, 71-96 (2008).
5. Moore RG, MacLaughlan S, Bast RC Jr: Current state of biomarker development for clinical application in epithelial ovarian cancer. Gynecol. Oncol. 116(2), 240-245 (2010).
6. Clarke-Pearson DL: Clinical practice. Screening for ovarian cancer. N. Engl. J. Med. 361(2), 170-177 (2009).
7. Rosenthal AN, Menon U, Jacobs IJ: Screening for ovarian cancer. Clin. Obstet. Gynecol. 49(3), 433-447 (2006).
8. Barker PE, Wagner PD, Stein SE, Bunk DM, Srivastava S, Omenn GS: Standards for plasma and serum proteomics in early cancer detection: a needs assessment report from the national institute of standards and technology-National Cancer Institute Standards, Methods, Assays, Reagents and Technologies Workshop, August 18-19, 2005. Clin. Chem. 52(9), 1669-1674 (2006).
9. Coombes KR, Morris JS, Hu J, Edmonson SR, Baggerly KA: Serum proteomics profling-a young technology begins to mature. Nat. Biotechnol. 23(3), 291-292 (2005).
10. Balch C, Montgomery JS, Paik HI et al.: New anti-cancer strategies: epigenetic therapies and biomarkers. Front. Biosci. 10, 1897-1931 (2005).
11. Laird PW: The power and the promise of DNA methylation markers. Nat. Rev. Cancer 3(4), 253-266 (2003).
12. Balch C, Fang F, Matei DE, Huang TH, Nephew KP: Minireview: epigenetic changes in ovarian cancer. Endocrinology 150(9), 4003-4011 (2009).
13. Balch C, Huang TH, Brown R, Nephew KP: The epigenetics of ovarian cancer drug resistance and resensitization. Am. J. Obstet. Gynecol. 191(5), 1552-1572 (2004).
14. Barton CA, Hacker NF, Clark SJ, O'Brien PM: DNA methylation changes in ovarian cancer: implications for early diagnosis, prognosis and treatment. Gynecol. Oncol. 109(1), 129-139 (2008).
15. Ozols RF: Systemic therapy for ovarian cancer: current status and new treatments. Semin. Oncol. 33(2 Suppl. 6), S3-S11 (2006).
16. Yap TA, Carden CP, Kaye SB: Beyond chemotherapy: targeted therapies in ovarian cancer. Nat. Rev. Cancer 9(3), 167-181 (2009).
17. Fang F, Balch C, Schilder J et al.: A Phase I and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer. Cancer (2010) (In press).
18. Yoo CB, Jones PA: Epigenetic therapy of cancer: past, present and future. 5(1), 37-50 (2006).
19. Sorosky JI: Endometrial cancer. Obstet. Gynecol. 111(2 Pt 1), 436-447 (2008).
20. Brown ML, Riley GF, Schussler N, Etzioni R: Estimating health care costs related to cancer treatment from SEER-Medicare data. Med. Care 40(Suppl. 8), IV-104-IV-117 (2002).
21. Allard JE, Maxwell GL: Race disparities between black and white women in the incidence, treatment, and prognosis of endometrial cancer. Cancer Control 16(1), 53-56 (2009).
22. Santin AD, Bellone S, Siegel ER et al.: Racial differences in the overexpression of epidermal growth factor type II receptor (HER2/neu): a major prognostic indicator in uterine serous papillary cancer. Am. J. Obstet. Gynecol. 192(3), 813-818 (2005).
23. Powell MA, Mutch DG, Rader JS, Herzog TJ, Huang TH, Goodfellow PJ: Ribosomal DNA methylation in patients with endometrial carcinoma: an independent prognostic marker. Cancer 94(11), 2941-2952 (2002).
24. Hecht JL, Mutter GL: Molecular and pathologic aspects of endometrial carcinogenesis. J. Clin. Oncol. 24(29), 4783-4791 (2006).
25. Bokhman JV: Two pathogenetic types of endometrial carcinoma. Gynecol. Oncol. 15(1), 10-17 (1983).
26. Shang Y: Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nat. Rev. Cancer 6(5), 360-368 (2006).
27. Zhou XC, Dowdy SC, Podratz KC, Jiang SW: Epigenetic considerations for endometrial cancer prevention, diagnosis and treatment. Gynecol. Oncol. 107(1), 143-153 (2007).
28. Lee CM, Szabo A, Shrieve DC, Macdonald OK, Gaffney DK: Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA 295(4), 389-397 (2006). (Pubitemid 43144975)
29. Carey MS, Gawlik C, Fung-Kee-Fung M, Chambers A, Oliver T: Systematic review of systemic therapy for advanced or recurrent endometrial cancer. Gynecol. Oncol. 101(1), 158-167 (2006).
30. Gadducci A, Tana R, Cosio S, Fanucchi A, Genazzani AR: Molecular target therapies in endometrial cancer: from the basic research to the clinic. Gynecol. Endocrinol. 24(5), 239-249 (2008).
31. Chaudhry P, Asselin E: Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr. Relat. Cancer 16(2), 363-380 (2009).
32. Decruze SB, Green JA: Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int. J. Gynecol. Cancer 17(5), 964-978 (2007).
33. Mellor HR, Callaghan R: Resistance to chemotherapy in cancer: a complex and integrated cellular response. Pharmacology 81(4), 275-300 (2008).
34. Eckstein N, Servan K, Hildebrandt B et al.: Hyperactivation of the insulin-like growth factor receptor I signaling pathway is an essential event for cisplatin resistance of ovarian cancer cells. Cancer Res. 69(7), 2996-3003 (2009).
35. Lu L, Katsaros D, de la Longrais IA, Sochirca O, Yu H: Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis. Cancer Res. 67(21), 10117-10122 (2007).
36. Wiley A, Katsaros D, Chen H et al.: Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential. Cancer 107(2), 299-308 (2006).
37. Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB: Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat. Rev. Drug Discov. 8(10), 806-823 (2009).
38. Dean M, Fojo T, Bates S: Tumour stem cells and drug resistance. Nat. Rev. Cancer 5(4), 275-284 (2005).
39. Zhang S, Balch C, Chan MW et al.: Identifcation and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 68(11), 4311-4320 (2008).
40. Alvero AB, Chen R, Fu HH et al.: Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle 8(1), 158-166 (2009).
41. + ovarian cancer cells. Oncogene 28(2), 209-218 (2009).
42. Curley MD, Therrien VA, Cummings CL et al.: CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells 27(12), 2875-2883 (2009).
43. Friel AM, Sergent PA, Patnaude C et al.: Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells. Cell Cycle 7(2), 242-249 (2008).
44. Hubbard SA, Friel AM, Kumar B, Zhang L, Rueda BR, Gargett CE: Evidence for cancer stem cells in human endometrial carcinoma. Cancer Res. 69(21), 8241-8248 (2009).
45. Rutella S, Bonanno G, Procoli A et al.: Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors. Clin. Cancer Res. 15(13), 4299-4311 (2009).
46. Boyer LA, Plath K, Zeitlinger J et al.: Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441(7091), 349-353 (2006).
47. Bibikova M, Chudin E, Wu B et al.: Human embryonic stem cells have a unique epigenetic signature. Genome Res. 16(9), 1075-1083 (2006).
48. Sasaki H, Matsui Y: Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat. Rev. Genet. 9(2), 129-140 (2008).
49. Jones PA, Baylin SB: The epigenomics of cancer. Cell 128(4), 683-692 (2007).
50. Bestor TH: The host defence function of genomic methylation patterns. Novartis Found. Symp. 214, 187-195; discussion 195-189, 228-232 (1998).
51. Esteller M: Epigenetics in cancer. N. Engl. J. Med. 358(11), 1148-1159 (2008).
52. Cedar H, Bergman Y: Linking DNA methylation and histone modifcation: patterns and paradigms. Nat. Rev. Genet. 10(5), 295-304 (2009).
53. Campos EI, Reinberg D: Histones: annotating chromatin. Annu. Rev. Genet. 43, 559-599 (2009).
54. Mikkelsen TS, Ku M, Jaffe DB et al.: Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153), 553-560 (2007).
55. Gan Q, Yoshida T, McDonald OG, Owens GK: Concise review: epigenetic mechanisms contribute to pluripotency and cell lineage determination of embryonic stem cells. Stem Cells 25(1), 2-9 (2007).
56. Ohm JE, McGarvey KM, Yu X et al.: A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat. Genet. 39(2), 237-242 (2007).
57. Rountree MR, Bachman KE, Herman JG, Baylin SB: DNA methylation, chromatin inheritance, and cancer. Oncogene 20(24), 3156-3165 (2001).
58. Lee MG, Wynder C, Bochar DA, Hakimi MA, Cooch N, Shiekhattar R: Functional interplay between histone demethylase and deacetylase enzymes. Mol. Cell Biol. 26(17), 6395-6402 (2006).
59. Sparmann A, van Lohuizen M: Polycomb silencers control cell fate, development and cancer. Nat. Rev. Cancer 6(11), 846-856 (2006).
60. Schickel R, Boyerinas B, Park SM, Peter ME: MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27(45), 5959-5974 (2008).
61. Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 136(2), 215-233 (2009).
62. Friedman JM, Jones PA: MicroRNAs: critical mediators of differentiation, development and disease. Swiss Med. Wkly 139(33-34), 466-472 (2009).
63. Asli NS, Pitulescu ME, Kessel M: MicroRNAs in organogenesis and disease. Curr. Mol. Med. 8(8), 698-710 (2008).
64. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T: Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat. Genet. 39(5), 673-677 (2007).
65. Kent OA, Mendell JT: A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene 25(46), 6188-6196 (2006).
66. Krutzfeldt J, Rajewsky N, Braich R et al.: Silencing of microRNAs in vivo with 'antagomirs'. Nature 438(7068), 685-689 (2005).
67. Bonauer A, Carmona G, Iwasaki M et al.: MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324(5935), 1710-1713 (2009).
68. Chan TA, Glockner S, Yi JM et al.: Convergence of mutation and epigenetic alterations identifes common genes in cancer that predict for poor prognosis. PLoS Med. 5(5), E114 (2008).
69. Kurose K, Zhou X P, Araki T, Cannistra SA, Maher ER, Eng C: Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am. J. Pathol. 158(6), 2097-2106 (2001).
70. Fiegl H, Windbichler G, Mueller-Holzner E et al.: HOXA11 DNA methylation-a novel prognostic biomarker in ovarian cancer. Int. J. Cancer 123(3), 725-729 (2008).
71. Widschwendter M, Apostolidou S, Jones AA et al.: HOXA methylation in normal endometrium from premenopausal women is associated with the presence of ovarian cancer: a proof of principle study. Int. J. Cancer 125(9), 2214-2218 (2009).
72. Barbolina MV, Adley BP, Kelly DL et al.: Downregulation of connective tissue growth factor by three-dimensional matrix enhances ovarian carcinoma cell invasion. Int. J. Cancer 125(4), 816-825 (2009).
73. Kikuchi R, Tsuda H, Kanai Y et al.: Promoter hypermethylation contributes to frequent inactivation of a putative conditional tumor suppressor gene connective tissue growth factor in ovarian cancer. Cancer Res. 67(15), 7095-7105 (2007).
74. Barton CA, Gloss BS, Qu W et al.: Collagen and calcium-binding EGF domains 1 is frequently inactivated in ovarian cancer by aberrant promoter hypermethylation and modulates cell migration and survival. Br. J. Cancer 102(1), 87-96 (2010).
75. Rathi A, Virmani AK, Schorge JO et al.: Methylation profles of sporadic ovarian tumors and nonmalignant ovaries from high-risk women. Clin. Cancer Res. 8(11), 3324-3331 (2002).
76. Makarla PB, Saboorian MH, Ashfaq R et al.: Promoter hypermethylation profle of ovarian epithelial neoplasms. Clin. Cancer Res. 11(15), 5365-5369 (2005).
77. Sawada K, Mitra AK, Radjabi AR et al.: Loss of E-cadherin promotes ovarian cancer metastasis via a 5-integrin, which is a therapeutic target. Cancer Res. 68(7), 2329-2339 (2008).
78. Issa JP: CpG island methylator phenotype in cancer. Nat. Rev. Cancer 4(12), 988-993 (2004).
79. Teodoridis JM, Hardie C, Brown R: CpG island methylator phenotype (CIMP) in cancer: causes and implications. Cancer Lett. 268(2), 177-186 (2008).
80. Ahluwalia A, Hurteau JA, Bigsby RM, Nephew KP: DNA methylation in ovarian cancer. II. Expression of DNA methyltransferases in ovarian cancer cell lines and normal ovarian epithelial cells. Gynecol. Oncol. 82(2), 299-304 (2001).
81. Ehrlich M, Woods CB, Yu MC et al.: Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors. Oncogene 25(18), 2636-2645 (2006).
82. Strathdee G, Appleton K, Illand M et al.: Primary ovarian carcinomas display multiple methylator phenotypes involving known tumor suppressor genes. Am. J. Pathol. 158(3), 1121-1127 (2001).
83. Furlan D, Carnevali I, Marcomini B et al.: The high frequency of de novo promoter methylation in synchronous primary endometrial and ovarian carcinomas. Clin. Cancer Res. 12(11 Pt 1), 3329-3336 (2006).
84. Ahluwalia A, Yan P, Hurteau JA et al.: DNA methylation and ovarian cancer. I. Analysis of CpG island hypermethylation in human ovarian cancer using differential methylation hybridization. Gynecol. Oncol. 82(2), 261-268 (2001).
85. Wei SH, Balch C, Paik HH et al.: Prognostic DNA methylation biomarkers in ovarian cancer. Clin. Cancer Res. 12(9), 2788-2794 (2006).
86. Wei SH, Chen CM, Strathdee G et al.: Methylation microarray analysis of late-stage ovarian carcinomas distinguishes progression-free survival in patients and identifes candidate epigenetic markers. Clin. Cancer Res. 8(7), 2246-2252 (2002).
87. Ibanez de Caceres I, Battagli C, Esteller M et al.: Tumor cell-specifc BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fuid from ovarian cancer patients. Cancer Res. 64(18), 6476-6481 (2004).
88. Gifford G, Paul J, Vasey PA, Kaye SB, Brown R: The acquisition of hMLH1 methylation in plasma DNA after chemotherapy predicts poor survival for ovarian cancer patients. Clin. Cancer Res. 10(13), 4420-4426 (2004).
89. Watanabe Y, Ueda H, Etoh T et al.: A change in promoter methylation of hMLH1 is a cause of acquired resistance to platinum-based chemotherapy in epithelial ovarian cancer. Anticancer Res. 27(3B), 1449-1452 (2007).
90. Helleman J, van Staveren IL, Dinjens WN et al.: Mismatch repair and treatment resistance in ovarian cancer. BMC Cancer 6, 201 (2006).
91. Nicholson LJ, Smith PR, Hiller L et al.: Epigenetic silencing of argininosuccinate synthetase confers resistance to platinum-induced cell death but collateral sensitivity to arginine auxotrophy in ovarian cancer. Int. J. Cancer 125(6), 1454-1463 (2009).
92. Yap OW, Bhat G, Liu L, Tollefsbol TO: Epigenetic modifcations of the estrogen receptor b gene in epithelial ovarian cancer cells. Anticancer Res. 29(1), 139-144 (2009).
93. Su HY, Lai HC, Lin YW et al.: Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway. Int. J. Cancer DOI: 10.1002/ijc.25083 (2009) (Epub ahead of print).
94. Strathdee G, MacKean MJ, Illand M, Brown R: A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancer. Oncogene 18(14), 2335-2341 (1999).
95. Strathdee G, Vass JK, Oien KA, Siddiqui N, Curto-Garcia J, Brown R: Demethylation of the MCJ gene in stage III/IV epithelial ovarian cancer and response to chemotherapy. Gynecol. Oncol. 97(3), 898-903 (2005).
96. Hatle KM, Neveu W, Dienz O et al.: Methylation-controlled J protein promotes c-Jun degradation to prevent ABCB1 transporter expression. Mol. Cell Biol. 27(8), 2952-2966 (2007).
97. Song J, Shih Ie M, Chan DW, Zhang Z: Suppression of annexin A11 in ovarian cancer: implications in chemoresistance. Neoplasia 11(6), 605-614 (2009).
98. Widschwendter M, Jiang G, Woods C et al.: DNA hypomethylation and ovarian cancer biology. Cancer Res. 64(13), 4472-4480 (2004).
99. Shao C, Lacey M, Dubeau L, Ehrlich M: Hemimethylation footprints of DNA demethylation in cancer. Epigenetics 4(3), 165-175 (2009).
100. Pattamadilok J, Huapai N, Rattanatanyong P et al.: LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer. Int. J. Gynecol. Cancer 18(4), 711-717 (2008).
101. Lee PS, Teaberry VS, Bland AE et al.: Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer. Int. J. Cancer 126(6), 1378-1389 (2010).
102. Litkouhi B, Kwong J, Lo CM et al.: Claudin-4 overexpression in epithelial ovarian cancer is associated with hypomethylation and is a potential target for modulation of tight junction barrier function using a C-terminal fragment of Clostridium perfringens enterotoxin. Neoplasia 9(4), 304-314 (2007).
103. Woloszynska-Read A, James SR, Link PA, Yu J, Odunsi K, Karpf AR: DNA methylation-dependent regulation of BORIS/CTCFL expression in ovarian cancer. Cancer Immun. 7, 21 (2007).
104. Bram EE, Stark M, Raz S, Assaraf YG: Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance. Neoplasia 11(12), 1359-1370 (2009).
105. Izutsu N, Maesawa C, Shibazaki M et al.: Epigenetic modifcation is involved in aberrant expression of class III b-tubulin, TUBB3, in ovarian cancer cells. Int. J. Oncol. 32(6), 1227-1235 (2008).
106. Gupta A, Godwin AK, Vanderveer L, Lu A, Liu J: Hypomethylation of the synuclein g gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma. Cancer Res. 63(3), 664-673 (2003).
107. Rose SL, Fitzgerald MP, White NO et al.: Epigenetic regulation of maspin expression in human ovarian carcinoma cells. Gynecol. Oncol. 102(2), 319-324 (2006).
108. Honda H, Pazin MJ, D'Souza T, Ji H, Morin PJ: Regulation of the CLDN3 gene in ovarian cancer cells. Cancer Biol. Ther. 6(11), 1733-1742 (2007).
109. Choi YL, Kim J, Kwon MJ et al.: Expression profle of tight junction protein claudin 3 and claudin 4 in ovarian serous adenocarcinoma with prognostic correlation. Histol. Histopathol. 22(11), 1185-1195 (2007).
110. Weichert W, Denkert C, Noske A et al.: Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas. Neoplasia 10(9), 1021-1027 (2008).
111. Caslini C, Capo-chichi CD, Roland IH, Nicolas E, Yeung AT, Xu XX: Histone modifcations silence the GATA transcription factor genes in ovarian cancer. Oncogene 25(39), 5446-5461 (2006).
112. Strait KA, Dabbas B, Hammond EH, Warnick CT, Iistrup SJ, Ford CD: 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. 1(13), 1181-1190 (2002).
113. Kwon MJ, Kim SS, Choi YL et al.: Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with loss of repressive histone modifcations. Carcinogenesis DOI:10.1093/carcin/bgp336 (2010) (Epub ahead of print).
114. Abbosh PH, Montgomery JS, Starkey JA et al.: Dominant-negative histone H3 lysine 27 mutant derepresses silenced tumor suppressor genes and reverses the drug-resistant phenotype in cancer cells. Cancer Res. 66(11), 5582-5591 (2006).
115. Merritt WM, Lin YG, Han LY et al.: Dicer, Drosha, and outcomes in patients with ovarian cancer. N. Engl. J. Med. 359(25), 2641-2650 (2008).
116. Pampalakis G, Diamandis EP, Katsaros D, Sotiropoulou G: Down-regulation of dicer expression in ovarian cancer tissues. Clin. Biochem. 43(3), 324-327 (2010).
117. Zhang L, Volinia S, Bonome T et al.: Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc. Natl Acad. Sci. USA 105(19), 7004-7009 (2008).
118. Laios A, O'Toole S, Flavin R et al.: Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol. Cancer 7, 35 (2008).
119. Zhang L, Huang J, Yang N et al.: microRNAs exhibit high frequency genomic alterations in human cancer. Proc. Natl Acad. Sci. USA 103(24), 9136-9141 (2006).
120. Faggad A, Budczies J, Tchernitsa O et al.: Prognostic signifcance of Dicer expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression. J. Pathol. 220(3), 382-391 (2010).
121. Brueckner B, Stresemann C, Kuner R et al.: The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 67(4), 1419-1423 (2007).
122. Lee CH, Subramanian S, Beck AH et al.: MicroRNA profling of BRCA1/2 mutation-carrying and non-mutation-carrying high-grade serous carcinomas of ovary. PLoS One 4(10), E7314 (2009).
123. Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat. Rev. Cancer 6(11), 857-866 (2006).
124. Bhattacharya R, Nicoloso M, Arvizo R et al.: MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer. Cancer Res. 69(23), 9090-9095 (2009).
125. Yang H, Kong W, He L et al.: MicroRNA expression profling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 68(2), 425-433 (2008).
126. Iorio MV, Visone R, Di Leva G et al.: MicroRNA signatures in human ovarian cancer. Cancer Res. 67(18), 8699-8707 (2007).
127. Varambally S, Cao Q, Mani RS et al.: Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322(5908), 1695-1699 (2008).
128. Dahiya N, Sherman-Baust CA, Wang TL et al.: MicroRNA expression and identifcation of putative miRNA targets in ovarian cancer. PLoS One 3(6), E2436 (2008).
129. Nam EJ, Yoon H, Kim SW et al.: MicroRNA expression profles in serous ovarian carcinoma. Clin. Cancer Res. 14(9), 2690-2695 (2008).
130. Eitan R, Kushnir M, Lithwick-Yanai G et al.: Tumor microRNA expression patterns associated with resistance to platinum based chemotherapy and survival in ovarian cancer patients. Gynecol. Oncol. 114(2), 253-259 (2009).
131. Hu X, Macdonald DM, Huettner PC et al.: A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer. Gynecol. Oncol. 114(3), 457-464 (2009).
132. Shimono Y, Zabala M, Cho RW et al.: Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138(3), 592-603 (2009).
133. Campan M, Weisenberger DJ, Laird PW: DNA methylation profles of female steroid hormone-driven human malignancies. Curr. Top. Microbiol. Immunol. 310, 141-178 (2006).
134. Sasaki M, Kaneuchi M, Fujimoto S, Tanaka Y, Dahiya R: Hypermethylation can selectively silence multiple promoters of steroid receptors in cancers. Mol. Cell Endocrinol. 202(1-2), 201-207 (2003).
135. Kang S, Kim JW, Kang GH et al.: Comparison of DNA hypermethylation patterns in different types of uterine cancer: cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma. Int. J. Cancer 118(9), 2168-2171 (2006).
136. Yanokura M, Banno K, Susumu N et al.: Hypermethylation in the p16 promoter region in the carcinogenesis of endometrial cancer in Japanese patients. Anticancer Res. 26(2A), 851-856 (2006).
137. Wong YF, Chung TK, Cheung TH et al.: Methylation of p16INK4A in primary gynecologic malignancy. Cancer Lett. 136(2), 231-235 (1999).
138. Whitcomb BP, Mutch DG, Herzog TJ, Rader JS, Gibb RK, Goodfellow PJ: Frequent HOXA11 and THBS2 promoter methylation, and a methylator phenotype in endometrial adenocarcinoma. Clin. Cancer Res. 9(6), 2277-2287 (2003).
139. Esteller M, Fraga MF, Guo M et al.: DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum. Mol. Genet. 10(26), 3001-3007 (2001).
140. Yeh KT, Yang MY, Liu TC et al.: Abnormal expression of period 1 (PER1) in endometrial carcinoma. J. Pathol. 206(1), 111-120 (2005).
141. Gurin CC, Federici MG, Kang L, Boyd J: Causes and consequences of microsatellite instability in endometrial carcinoma. Cancer Res. 59(2), 462-466 (1999).
142. Jacinto FV, Esteller M: Mutator pathways unleashed by epigenetic silencing in human cancer. Mutagenesis 22(4), 247-253 (2007).
143. Rimel BJ, Huettner P, Powell MA, Mutch DG, Goodfellow PJ: Absence of MGMT promoter methylation in endometrial cancer. Gynecol. Oncol. 112(1), 224-228 (2009).
144. Loeb LA, Bielas JH, Beckman RA: Cancers exhibit a mutator phenotype: clinical implications. Cancer Res. 68(10), 3551-3557; discussion 3557 (2008).
145. Zighelboim I, Goodfellow PJ, Gao F et al.: Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type. J. Clin. Oncol. 25(15), 2042-2048 (2007).
146. Salvesen HB, MacDonald N, Ryan A et al.: PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int. J. Cancer 91(1), 22-26 (2001).
147. Shibata D, Mori Y, Cai K et al.: RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas. Int. J. Cancer 119(4), 801-806 (2006).
148. Yamaguchi S, Asanoma K, Takao T, Kato K, Wake N: Homeobox gene HOPX is epigenetically silenced in human uterine endometrial cancer and suppresses estrogen-stimulated proliferation of cancer cells by inhibiting serum response factor. Int. J. Cancer 124(11), 2577-2588 (2009).
149. Zysman M, Saka A, Millar A, Knight J, Chapman W, Bapat B: Methylation of adenomatous polyposis coli in endometrial cancer occurs more frequently in tumors with microsatellite instability phenotype. Cancer Res. 62(13), 3663-3666 (2002).
150. Zighelboim I, Goodfellow PJ, Schmidt AP et al.: Differential methylation hybridization array of endometrial cancers reveals two novel cancer-specifc methylation markers. Clin. Cancer Res. 13(10), 2882-2889 (2007).
151. Varley KE, Mutch DG, Edmonston TB, Goodfellow PJ, Mitra RD: Intra-tumor heterogeneity of MLH1 promoter methylation revealed by deep single molecule bisulfte sequencing. Nucleic Acids Res. 37(14), 4603-4612 (2009).
152. Risinger JI, Maxwell GL, Chandramouli GV et al.: Gene expression profling of microsatellite unstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling. Cancer Res. 65(12), 5031-5037 (2005).
153. Katoh M: WNT signaling pathway and stem cell signaling network. Clin. Cancer Res. 13(14), 4042-4045 (2007).
154. Baylin SB, Ohm JE: Epigenetic gene silencing in cancer-a mechanism for early oncogenic pathway addiction? Nat. Rev. Cancer 6(2), 107-116 (2006).
155. Shapiro S, Kaufman DW, Slone D et al.: Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium. N. Engl. J. Med. 303(9), 485-489 (1980).
156. Kumar NS, Richer J, Owen G, Litman E, Horwitz KB, Leslie KK: Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action. Cancer Res. 58(9), 1860-1865 (1998).
157. Clarke CL, Sutherland RL: Progestin regulation of cellular proliferation. Endocr. Rev. 11(2), 266-301 (1990).
158. Uharcek P: Prognostic factors in endometrial carcinoma. J. Obstet. Gynaecol. Res. 34(5), 776-783 (2008).
159. Sasaki M, Kotcherguina L, Dharia A, Fujimoto S, Dahiya R: Cytosine-phosphoguanine methylation of estrogen receptors in endometrial cancer. Cancer Res. 61(8), 3262-3266 (2001).
160. Maeda K, Tsuda H, Hashiguchi Y et al.: Relationship between p53 pathway and estrogen receptor status in endometrioid-type endometrial cancer. Hum. Pathol. 33(4), 386-391 (2002).
161. Wu H, Chen Y, Liang J et al.: Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature 438(7070), 981-987 (2005).
162. Newbold RR, Padilla-Banks E, Jefferson WN: Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations. Endocrinology 147(Suppl. 6), S11-S17 (2006).
163. Li S, Washburn KA, Moore R et al.: Developmental exposure to diethylstilbestrol elicits demethylation of estrogen-responsive lactoferrin gene in mouse uterus. Cancer Res. 57(19), 4356-4359 (1997).
164. Liu JR, Opipari AW, Tan L et al.: Dysfunctional apoptosome activation in ovarian cancer: implications for chemoresistance. Cancer Res. 62(3), 924-931 (2002).
165. Li AJ, Baldwin RL, Karlan BY: Estrogen and progesterone receptor subtype expression in normal and malignant ovarian epithelial cell cultures. Am. J. Obstet. Gynecol. 189(1), 22-27 (2003).
166. Gargett CE: Identifcation and characterisation of human endometrial stem/progenitor cells. Aust. NZ J. Obstet. Gynaecol. 46(3), 250-253 (2006).
167. Chan RW, Gargett CE: Identifcation of label-retaining cells in mouse endometrium. Stem Cells 24(6), 1529-1538 (2006).
168. Kim JY, Tavare S, Shibata D: Counting human somatic cell replications: methylation mirrors endometrial stem cell divisions. Proc. Natl Acad. Sci. USA 102(49), 17739-17744 (2005).
169. Melo SA, Ropero S, Moutinho C et al.: A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat. Genet. 41(3), 365-370 (2009).
170. Myatt SS, Wang J, Monteiro LJ et al.: Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res. 70(1), 367-377 (2010).
171. Zhou L, Qi X, Potashkin JA, Abdul-Karim FW, Gorodeski GI: MicroRNAs miR-186 and miR-150 down-regulate expression of the pro-apoptotic purinergic P2X7 receptor by activation of instability sites at the 3́-untranslated region of the gene that decrease steady-state levels of the transcript. J. Biol. Chem. 283(42), 28274-28286 (2008).
172. Luthra R, Singh RR, Luthra MG et al.: MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene 27(52), 6667-6678 (2008).
173. Huang YW, Liu JC, Deatherage DE et al.: Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res. 69(23), 9038-9046 (2009).
174. Resnick KE, Alder H, Hagan JP, Richardson DL, Croce CM, Cohn DE: The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform. Gynecol. Oncol. 112(1), 55-59 (2009).
175. Resnick KE, Cohn DE, Ivanov I, Liu C, Taccioli C, Croce CM: miRNA profle and advanced stage endometrial cancer. J. Clin. Oncol. 26 (May 20 Supplement) (2008) (Abstract 5561).
176. Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK: MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol. Cancer Ther. 8(5), 1055-1066 (2009).
177. Boren T, Xiong Y, Hakam A et al.: MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis. Gynecol. Oncol. 110(2), 206-215 (2008).
178. Nam S, Li M, Choi K, Balch C, Kim S, Nephew KP: MicroRNA and mRNA integrated analysis (MMIA): a web tool for examining biological functions of microRNA expression. Nucleic Acids Res. 37(Web Server issue), W356-W362 (2009).
179. Kuokkanen S, Chen B, Ojalvo L, Benard L, Santoro N, Pollard JW: Genomic profling of microRNAs and messenger RNAs reveals hormonal regulation in microRNA expression in human endometrium. Biol. Reprod. 82(4), 791-801 (2009).
180. Pan Q, Luo X, Toloubeydokhti T, Chegini N: The expression profle of micro-RNA in endometrium and endometriosis and the infuence of ovarian steroids on their expression. Mol. Hum. Reprod. 13(11), 797-806 (2007).
181. Matei DE, Nephew KP: Epigenetic therapies for chemoresensitization of epithelial ovarian cancer. Gynecol. Oncol. 116(2), 195-201 (2010).
182. Takai N, Kawamata N, Walsh CS et al.: Discovery of epigenetically masked
183. Nguyen CT, Weisenberger DJ, Velicescu M et al.: Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2́-deoxycytidine. Cancer Res. 62(22), 6456-6461 (2002).
184. Yoo CB, Jeong S, Egger G et al.: Delivery of 5-aza-2́-deoxycytidine to cells using oligodeoxynucleotides. Cancer Res. 67(13), 6400-6408 (2007).
185. Balch C, Yan P, Craft T et al.: Antimitogenic and chemosensitizing effects of the methylation inhibitor zebularine in ovarian cancer. Mol. Cancer Ther. 4(10), 1505-1514 (2005).
186. Leu YW, Rahmatpanah F, Shi H et al.: Double RNA interference of DNMT3b and DNMT1 enhances DNA demethylation and gene reactivation. Cancer Res. 63(19), 6110-6115 (2003).
187. Plummer R, Vidal L, Griffin M et al.: 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. 15(9), 3177-3183 (2009).
188. Siedlecki P, Garcia Boy R, Musch T et al.: Discovery of two novel, small-molecule inhibitors of DNA methylation. J. Med. Chem. 49(2), 678-683 (2006).
189. Brueckner B, Garcia Boy R, Siedlecki P et al.: Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 65(14), 6305-6311 (2005).
190. Datta J, Ghoshal K, Denny WA et al.: A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Cancer Res. 69(10), 4277-4285 (2009).
191. Candelaria M, Gallardo-Rincon D, Arce C et al.: A Phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann. Oncol. 18(9), 1529-1538 (2007).
192. Minucci S, Pelicci PG: Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer 6(1), 38-51 (2006).
193. Qiu L, Burgess A, Fairlie DP, Leonard H, Parsons PG, Gabrielli BG: Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells. Mol. Biol. Cell 11(6), 2069-2083 (2000).
194. Strait KA, Warnick CT, Ford CD, Dabbas B, Hammond EH, Ilstrup SJ: Histone deacetylase inhibitors induce G2-checkpoint arrest and apoptosis in cisplatinum-resistant ovarian cancer cells associated with overexpression of the Bcl-2-related protein Bad. Mol. Cancer Ther. 4(4), 603-611 (2005).
195. Choudhary C, Kumar C, Gnad F et al.: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325(5942), 834-840 (2009).
196. Batty N, Malouf GG, Issa JP: Histone deacetylase inhibitors as anti-neoplastic agents. Cancer Lett. 280(2), 192-200 (2009).
197. Plumb JA, Finn PW, Williams RJ et al.: Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol. Cancer Ther. 2(8), 721-728 (2003).
198. Qian X, LaRochelle WJ, Ara G et al.: Activity of PXD101, a histone deacetylase inhibitor, in preclinical ovarian cancer studies. Mol. Cancer Ther. 5(8), 2086-2095 (2006).
199. 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).
200. Takai N, Desmond JC, Kumagai T et al.: Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin. Cancer Res. 10(3), 1141-1149 (2004).
201. Ahn MY, Jung JH, Na YJ, Kim HS: A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells. Gynecol. Oncol. 108(1), 27-33 (2008).
202. Ahn MY, Chung HY, Choi WS, Lee BM, Yoon S, Kim HS: Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4. Int. J. Oncol. 36(1), 125-131 (2010).
203. Takai N, Ueda T, Nishida M, Nasu K, Narahara H: Anticancer activity of MS-275, a novel histone deacetylase inhibitor, against human endometrial cancer cells. Anticancer Res. 26(2A), 939-945 (2006).
204. Jiang S, Dowdy SC, Meng XW et al.: Histone deacetylase inhibitors induce apoptosis in both Type I and Type II endometrial cancer cells. Gynecol. Oncol. 105(2), 493-500 (2007).
205. Takai N, Ueda T, Nishida M, Nasu K, Narahara H: M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells. Gynecol. Oncol. 101(1), 108-113 (2006).
206. Rocha W, Sanchez R, Deschenes J et al.: Opposite effects of histone deacetylase inhibitors on glucocorticoid and estrogen signaling in human endometrial Ishikawa cells. Mol. Pharmacol. 68(6), 1852-1862 (2005).
207. Modesitt SC, Sill M, Hoffman JS, Bender DP: A Phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol. Oncol. 109(2), 182-186 (2008).
208. Mackay H, Hirte HW, Covens A et al.: A Phase II trial of the histone deacetylase inhibitor belinostat (PXD101) in patients with platinum resistant epithelial ovarian tumors and micropapillary/borderline (LMP) ovarian tumors. A PMH Phase II consortium trial. J. Clin. Oncol. 26(15S) (May 20 Supplement) (2008) (Abstract 5518).
209. Morey L, Brenner C, Fazi F et al.: MBD3, a component of the NuRD complex, facilitates chromatin alteration and deposition of epigenetic marks. Mol. Cell Biol. 28(19), 5912-5923 (2008).
210. Terasawa K, Sagae S, Toyota M et al.: Epigenetic inactivation of TMS1/ASC in ovarian cancer. Clin. Cancer Res. 10(6), 2000-2006 (2004).
211. Xiong Y, Dowdy SC, Gonzalez Bosquet J et al.: Epigenetic-mediated upregulation of progesterone receptor B gene in endometrial cancer cell lines. Gynecol. Oncol. 99(1), 135-141 (2005).
212. Shi H, Wei SH, Leu YW et al.: Triple analysis of the cancer epigenome: an integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation. Cancer Res. 63(9), 2164-2171 (2003).
213. Venturelli S, Armeanu S, Pathil A et al.: Epigenetic combination therapy as a tumor-selective treatment approach for hepatocellular carcinoma. Cancer 109(10), 2132-2141 (2007).
214. Cameron EE, Bachman KE, Myohanen 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).
215. Braiteh F, Soriano AO, Garcia-Manero G et al.: Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Clin. Cancer Res. 14(19), 6296-6301 (2008).
216. Plumb JA, Strathdee G, Sludden J, Kaye SB, Brown R: Reversal of drug resistance in human tumor xenografts by 2́-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res. 60(21), 6039-6044 (2000).
217. Lin CT, Lai HC, Lee HY et al.: Valproic acid resensitizes cisplatin-resistant ovarian cancer cells. Cancer Sci. 99(6), 1218-1226 (2008).
218. Yang YT, Balch C, Kulp SK, Mand MR, Nephew K P, Chen CS: A rationally designed histone deacetylase inhibitor with distinct antitumor activity against ovarian cancer. Neoplasia 11(6), 552-563 (2009).
219. Dowdy SC, Jiang S, Zhou XC et al.: Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells. Mol. Cancer Ther. 5(11), 2767-2776 (2006).
220. Appleton K, Mackay HJ, Judson I et al.: Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors. J. Clin. Oncol. 25(29), 4603-4609 (2007).
221. Glasspool RM, Gore M, Rustin G et al.: Randomized Phase II study of decitabine in combination with carboplatin compared with carboplatin alone in patients with recurrent advanced ovarian cancer. J. Clin. Oncol. 26(15S) (May 20 Supplement), (2009) (Abstract 5562).
222. Bast RC, Iyer RB, Hu W et al.: A Phase IIa study of a sequential regimen using azacitidine to reverse platinum resistance to carboplatin in patients with platinum resistant or refractory epithelial ovarian cancer. J. Clin. Oncol. 26(15S) (May 20 Supplement) (2008) (Abstract 3500).
223. Cooper AL, Greenberg VL, Lancaster PS, van Nagell JR Jr, Zimmer SG, Modesitt SC: In vitro and in vivo histone deacetylase inhibitor therapy with suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer. Gynecol. Oncol. 104(3), 596-601 (2006)
224. Dietrich CS 3rd, Greenberg VL, DeSimone CP et al.: Suberoylanilide hydroxamic acid (SAHA) potentiates paclitaxel-induced apoptosis in ovarian cancer cell lines. Gynecol. Oncol. 116(1), 126-130 (2010).
225. Sonnemann J, Gange J, Pilz S et al.: Comparative evaluation of the treatment effcacy of suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer cell lines and primary ovarian cancer cells from patients. BMC Cancer 6, 183 (2006).
226. Steele N, Finn P, Brown R, Plumb JA: Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo. Br. J. Cancer 100(5), 758-763 (2009).
227. Simpson AJ, Caballero OL, Jungbluth A, Chen Y T, Old LJ: Cancer/testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 5(8), 615-625 (2005).
228. Karpf AR: A potential role for epigenetic modulatory drugs in the enhancement of cancer/germ-line antigen vaccine effcacy. Epigenetics 1(3), 116-120 (2006).
229. Poleshko A, Einarson MB, Shalginskikh N et al.: Identifcation of a functional network of human epigenetic silencing factors. J. Biol. Chem. 285(1), 422-433 (2010).
230. Melnikov A, Scholtens D, Godwin A, Levenson V: Differential methylation profle of ovarian cancer in tissues and plasma. J. Mol. Diagn. 11(1), 60-65 (2009).
231. Huang Y W, Jansen RA, Fabbri E et al.: Identifcation of candidate epigenetic biomarkers for ovarian cancer detection. Oncol. Rep. 22(4), 853-861 (2009).
232. Feng Q, Deftereos G, Hawes SE et al.: DNA hypermethylation, Her-2/neu overexpression and p53 mutations in ovarian carcinoma. Gynecol. Oncol. 111(2), 320-329 (2008).
233. Wu Q, Lothe RA, Ahlquist T et al.: DNA methylation profling of ovarian carcinomas and their in vitro models identifes HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets. Mol. Cancer 6, 45 (2007).
234. Akahira J, Sugihashi Y, Suzuki T et al.: Decreased expression of 14-3-3 s is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation. Clin. Cancer Res. 10(8), 2687-2693 (2004).
235. Socha MJ, Said N, Dai Y et al.: Aberrant promoter methylation of SPARC in ovarian cancer. Neoplasia 11(2), 126-135 (2009).
236. Staub J, Chien J, Pan Y et al.: Epigenetic silencing of HSulf-1 in ovarian cancer: implications in chemoresistance. Oncogene 26(34), 4969-4978 (2007).
237. Chaudhry P, Srinivasan R, Patel FD: Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Cancer Invest. 27(8), 877-884 (2009).
238. Swisher EM, Gonzalez RM, Taniguchi T et al.: Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas. Mol. Cancer 8, 48 (2009).
239. Teodoridis JM, Hall J, Marsh S et al.: CpG island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res. 65(19), 8961-8967 (2005).
240. Chou JL, Su HY, Chen LY et al.: Promoter hypermethylation of FBXO32, a novel TGF-b/SMAD4 target gene and tumor suppressor, is associated with poor prognosis in human ovarian cancer. Lab. Invest. 90(3), 414-425 (2010).
241. Su HY, Lai HC, Lin YW, Chou YC, Liu CY, Yu MH: An epigenetic marker panel for screening and prognostic prediction of ovarian cancer. Int. J. Cancer 124(2), 387-393 (2009).
242. Chan MW, Wei SH, Wen P et al.: Hypermethylation of 18S and 28S ribosomal DNAs predicts progression-free survival in patients with ovarian cancer. Clin. Cancer Res. 11(20), 7376-7383 (2005).
243. Muller HM, Millinger S, Fiegl H et al.: Analysis of methylated genes in peritoneal fuids of ovarian cancer patients: a new prognostic tool. Clin. Chem. 50(11), 2171-2173 (2004).
244. Yang N, Kaur S, Volinia S et al.: MicroRNA microarray identifes Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 68(24), 10307-10314 (2008).
245. Cowden Dahl KD, Dahl R, Kruichak JN, Hudson LG: The epidermal growth factor receptor responsive miR-125a represses mesenchymal morphology in ovarian cancer cells. Neoplasia 11(11), 1208-1215 (2009).
246. Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C: Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol. Oncol. 111(3), 478-486 (2008).
247. Zhu H, Wu H, Liu X et al.: Role of microRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem. Pharmacol. 76(5), 582-588 (2008).
248. Flavin R, Smyth P, Barrett C et al.: miR-29b expression is associated with disease-free survival in patients with ovarian serous carcinoma. Int. J. Gynecol. Cancer 19(4), 641-647 (2009).
249. Wyman SK, Parkin RK, Mitchell PS et al.: Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One 4(4), E5311 (2009).
250. Bearfoot JL, Choong DY, Gorringe KL, Campbell IG: Genetic analysis of cancer-implicated MicroRNA in ovarian cancer. Clin. Cancer Res. 14(22), 7246-7250 (2008).
251. Yang Y, Chaerkady R, Beer MA, Mendell JT, Pandey A: Identifcation of miR-21 targets in breast cancer cells using a quantitative proteomic approach. Proteomics 9(5), 1374-1384 (2009).
252. Boren T, Xiong Y, Hakam A et al.: MicroRNAs and their target messenger RNAs associated with ovarian cancer response to chemotherapy. Gynecol. Oncol. 113(2), 249-255 (2009).
253. Taylor DD, Gercel-Taylor C: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol. Oncol. 110(1), 13-21 (2008).
254. Bendoraite A, Knouf EC, Garg KS et al.: Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: evidence supporting a mesothelial-to-epithelial transition. Gynecol. Oncol. 116(1), 117-125 (2010).
255. Helleman J, Jansen MP, Burger C, van der Burg ME, Berns EM: Integrated genomics of chemotherapy resistant ovarian cancer: a role for extracellular matrix, TGFb and regulating microRNAs. Int. J. Biochem. Cell Biol. 42(1), 25-30 (2010).
256. Ji J, Yamashita T, Budhu A et al.: Identifcation of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology 50(2), 472-480 (2009).
257. Yu J, Ryan DG, Getsios S, Oliveira-Fernandes M, Fatima A, Lavker RM: MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proc. Natl Acad. Sci. USA 105(49), 19300-19305 (2008).
258. Fukao T, Fukuda Y, Kiga K et al.: An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profling. Cell 129(3), 617-631 (2007).
259. Wurdinger T, Tannous BA, Saydam O et al.: miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 14(5), 382-393 (2008).
260. Yang WT, Lewis MT, Hess K et al.: Decreased TGFb signaling and increased COX2 expression in high risk women with increased mammographic breast density. Breast Cancer Res. Treat 119(2), 305-314 (2010).
261. Nasser MW, Datta J, Nuovo G et al.: Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J. Biol. Chem. 283(48), 33394-33405 (2008).
262. Guo LM, Pu Y, Han Z et al.: MicroRNA-9 inhibits ovarian cancer cell growth through regulation of NF-kB1. FEBS J. 276(19), 5537-5546 (2009).
263. Chang TC, Yu D, Lee YS et al.: Widespread microRNA repression by Myc contributes to tumorigenesis. Nat. Genet. 40(1), 43-50 (2008).
264. Hossain A, Kuo MT, Saunders GF: Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol. Cell Biol. 26(21), 8191-8201 (2006).
265. Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS: MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137(4), 647-658 (2009).
266. Fasanaro P, Greco S, Lorenzi M et al.: An integrated approach for experimental target identifcation of hypoxia-induced miR-210. J. Biol. Chem. 284(50), 35134-35143 (2009).
267. Giannakakis A, Sandaltzopoulos R, Greshock J et al.: miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol. Ther. 7(2), 255-264 (2008).
268. Tavazoie SF, Alarcon C, Oskarsson T et al.: Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175), 147-152 (2008).
269. Abdelmohsen K, Srikantan S, Kuwano Y, Gorospe M: miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proc. Natl Acad. Sci. USA 105(51), 20297-20302 (2008).
270. Fiegl H, Gattringer C, Widschwendter A et al.: Methylated DNA collected by tampons-a new tool to detect endometrial cancer. Cancer Epidemiol. Biomarkers Prev. 13(5), 882-888 (2004).
271. Mhawech-Fauceglia P, Smiraglia DJ, Bshara W et al.: Prostate-specifc membrane antigen expression is a potential prognostic marker in endometrial adenocarcinoma. Cancer Epidemiol. Biomarkers Prev. 17(3), 571-577 (2008).
272. Jo H, Kim JW, Kang GH et al.: Association of promoter hypermethylation of the RASSF1A gene with prognostic parameters in endometrial cancer. Oncol. Res. 16(4), 205-209 (2006).
273. Suehiro Y, Okada T, Anno K et al.: Aneuploidy predicts outcome in patients with endometrial carcinoma and is related to lack of CDH13 hypermethylation. Clin. Cancer Res. 14(11), 3354-3361 (2008).
274. Wu W, Lin Z, Zhuang Z, Liang X: Expression profle of mammalian microRNAs in endometrioid adenocarcinoma. Eur. J. Cancer Prev. 18(1), 50-55 (2009).
275. Hiroki E, Akahira JI, Suzuki F et al.: Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas. Cancer Sci. 101(1), 241-249 (2009).
276. Chung TK, Cheung TH, Huen NY et al.: Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women. Int. J. Cancer 124(6), 1358-1365 (2009).
277. Orom UA, Nielsen FC, Lund AH: MicroRNA-10a binds the 5́UTR of ribosomal protein mRNAs and enhances their translation. Mol. Cell 30(4), 460-471 (2008).
278. Mayr D, Kanitz V, Anderegg B et al.: Analysis of gene amplifcation and prognostic markers in ovarian cancer using comparative genomic hybridization for microarrays and immunohistochemical analysis for tissue microarrays. Am. J. Clin. Pathol. 126(1), 101-109 (2006).
279. Kim YK, Yu J, Han TS et al.: Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer. Nucleic Acids Res. 37(5), 1672-1681 (2009).
280. Dalmay T, Edwards DR: MicroRNAs and the hallmarks of cancer. Oncogene 25(46), 6170-6175 (2006).
281. Lujambio A, Calin GA, Villanueva A et al.: A microRNA DNA methylation signature for human cancer metastasis. Proc. Natl Acad. Sci. USA 105(36), 13556-13561 (2008).
282. Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K: Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 315(5815), 1137-1140 (2007).
283. To KK, Zhan Z, Litman T, Bates SE: Regulation of ABCG2 expression at the 3' untranslated region of its mRNA through modulation of transcript stability and protein translation by a putative microRNA in the S1 colon cancer cell line. Mol. Cell Biol. 28(17), 5147-5161 (2008).
284. Toloubeydokhti T, Pan Q, Luo X, Bukulmez O, Chegini N: The expression and ovarian steroid regulation of endometrial micro-RNAs. Reprod Sci. 15(10), 993-1001 (2008).