Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer

Current Cancer Drug Targets

Volumn 8, Issue 6, 2008, Pages 509-521

  Zhao, Ronghua ^a   Casson, Alan G ^a  

^a UNIVERSITY OF SASKATCHEWAN   (Canada)

Author keywords

Barrett esophagus; DNA methylation; Epigenetics; Esophageal cancer; Genomic imprinting; Histone modification; Therapeutic targets

Indexed keywords

3 PHENYLSULFAMOYLCINNAMOHYDROXAMIC ACID; 4 [N (2 HYDROXYETHYL) N [2 (3 INDOLYL)ETHYL]AMINOMETHYL]CINNAMOHYDROXAMIC ACID; 5 AZA 2' DEOXYCYTIDINE; ANTISENSE OLIGONUCLEOTIDE; AZACITIDINE; CALPHOSTIN C; CISPLATIN; DNA; DNA METHYLTRANSFERASE INHIBITOR; EPIGALLOCATECHIN GALLATE; FLUCYTOSINE DEOXYRIBOSIDE; GENISTEIN; HISTONE; HISTONE DEACETYLASE INHIBITOR; HYDRALAZINE; NATURAL PRODUCT; PROCAINAMIDE; PROTEIN P53; PROTEIN P73; ROMIDEPSIN; SECRETED FRIZZLED RELATED PROTEIN 1; SECRETED FRIZZLED RELATED PROTEIN 4; TELOMERASE; TRANSCRIPTION FACTOR RUNX3; TRANSFORMING GROWTH FACTOR BETA; TRICHOSTATIN A; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT; ZEBULARINE;

ANTISENSE THERAPY; APOPTOSIS; BARRETT ESOPHAGUS; CELL CYCLE; CHROMOSOME 3P; CHROMOSOME 9P; COMBINATION CHEMOTHERAPY; DNA METHYLATION; DNA REPAIR; DOSE TIME EFFECT RELATION; DRUG EFFICACY; ENZYME INHIBITION; EPIGENETICS; ESOPHAGEAL ADENOCARCINOMA; ESOPHAGUS CANCER; GENOME IMPRINTING; HUMAN; MISMATCH REPAIR; PROMOTER REGION; REVIEW; SQUAMOUS CELL CARCINOMA; TUMOR CELL; TUMOR SUPPRESSOR GENE;

CARCINOMA, SQUAMOUS CELL; EPIGENESIS, GENETIC; ESOPHAGEAL NEOPLASMS; GENE THERAPY; HUMANS;

EID: 51349104893     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800908785699306     Document Type: Review

References (176)

1. Parkin, D. M.; Bray, F.; Ferlay, J.; Pisani, P. Global cancer statistics, 2002. CA Cancer J. Clin. 2005, 55, 74-108.
2. Forman, D. Review article: oesophago-gastric adenocarcinoma - an epidemiological perspective. Aliment. Pharmacol. Ther. 2004, 20(Suppl. 5), 55-60; discussion 61-52.
3. Lagergren, J.; Bergstrom, R.; Lindgren, A.; Nyren, O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N. Engl. J. Med. 1999, 340, 825-831.
4. Veugelers, P. J.; Porter, G. A.; Guernsey, D. L.; Casson, A. G. Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinoma. Dis. Esophagus 2006, 19, 321-328.
5. Brown, L. M.; Swanson, C. A.; Gridley, G.; Swanson, G. M.; Schoenberg, J. B.; Greenberg, R. S.; Silverman, D. T.; Pottern, L. M.; Hayes, R. B.; Schwartz, A. G.; et al. Adenocarcinoma of the esophagus: role of obesity and diet. J. Natl. Cancer Inst. 1995, 87, 104-109.
6. Mayne, S. T.; Risch, H. A.; Dubrow, R.; Chow, W. H.; Gammon, M. D.; Vaughan, T. L.; Farrow, D. C.; Schoenberg, J. B.; Stanford, J. L.; Ahsan, H.; West, A. B.; Rotterdam, H.; Blot, W. J.; Fraumeni, J. F., Jr. Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol. Biomarkers Prev. 2001, 10, 1055-1062.
7. Spechler, S. J. Clinical practice. Barrett's Esophagus. N. Engl. J. Med. 2002, 346, 836-842.
8. Casson, A. G. Role of molecular biology in the follow-up of patients who have Barrett's esophagus. Chest Surg. Clin. N. Am. 2002, 12, 93-111.
9. Reid, B. J.; Blount, P. L.; Rabinovitch, P.S. Biomarkers in Barrett's esophagus. Gastrointest. Endosc. Clin. N. Am. 2003, 13, 369-397.
10. McManus, D. T.; Olaru, A.; Meltzer, S. J. Biomarkers of esophageal adenocarcinoma and Barrett's esophagus. Cancer Res. 2004, 64, 1561-1569.
11. Wild, C. P.; Hardie, L. J. Reflux, Barrett's oesophagus and adenocarcinoma: burning questions. Nat. Rev. Cancer 2003, 3, 676-684.
12. Koppert, L. B.; Wijnhoven, B. P.; van Dekken, H.; Tilanus, H. W.; Dinjens, W. N. The molecular biology of esophageal adenocarcinoma. J. Surg. Oncol. 2005, 92, 169-190.
13. Lerut, T.; Coosemans, W.; Decker, G.; De Leyn, P.; Moons, J.; Nafteux, P.; Van Raemdonck, D. Surgical techniques. J. Surg. Oncol. 2005, 92, 218-229.
14. Feinberg, A. P. Phenotypic plasticity and the epigenetics of human disease. Nature 2007, 447, 433-440.
15. Li, E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet. 2002, 3, 662-673.
16. Bjornsson, H. T.; Fallin, M. D.; Feinberg, A. P. An integrated epigenetic and genetic approach to common human disease. Trends Genet. 2004, 20, 350-358.
17. Watanabe, M.; Takagi, A.; Matsuzaki, T.; Kami, D.; Toyota, M.; Hirokawa, Y.; Shiraishi, T. Knowledge of epigenetic influence for prostate cancer therapy. Curr. Cancer Drug Targets 2006, 6, 533-551.
18. Baylin, S. B.; Herman, J. G.; Graff, J. R.; Vertino, P. M.; Issa, J. P. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv. Cancer Res. 1998, 72, 141-196.
19. Esteller, M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat. Rev. Genet. 2007, 8, 286-298.
20. Sanders, S. L.; Portoso, M.; Mata, J.; Bahler, J.; Allshire, R. C.; Kouzarides, T. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 2004, 119, 603-614.
21. Feinberg, A. Genomic imprinting and cancer. In The genetic basis of human cancer; Vogelstein, B. & Kinzler, K.W. Eds.; McGraw-Hill: New York, 1998, pp. 95-107.
22. Diaz-Meyer, N.; Day, C. D.; Khatod, K.; Maher, E. R.; Cooper, W.; Reik, W.; Junien, C.; Graham, G.; Algar, E.; Der Kaloustian, V. M.; Higgins, M. J. Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. J. Med. Genet. 2003, 40, 797-801.
23. Jelinic, P.; Shaw, P. Loss of imprinting and cancer. J. Pathol. 2007, 211, 261-268.
24. Mancini-Dinardo, D.; Steele, S. J.; Levorse, J. M.; Ingram, R. S.; Tilghman, S. M. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev. 2006, 20, 1268-1282.
25. Umlauf, D.; Goto, Y.; Cao, R.; Cerqueira, F.; Wagschal, A.; Zhang, Y.; Feil, R. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Nat. Genet. 2004, 36, 1296-1300.
26. Guo, R. J.; Suh, E. R.; Lynch, J. P. The role of Cdx proteins in intestinal development and cancer. Cancer Biol. Ther. 2004, 3, 593-601.
27. Wong, N. A.; Wilding, J.; Bartlett, S.; Liu, Y.; Warren, B. F.; Piris, J.; Maynard, N.; Marshall, R.; Bodmer, W. F. CDX1 is an important molecular mediator of Barrett's metaplasia. Proc. Natl. Acad. Sci. USA 2005, 102, 7565-7570.
28. Shibagaki, I.; Shimada, Y.; Wagata, T.; Ikenaga, M.; Imamura, M.; Ishizaki, K. Allelotype analysis of esophageal squamous cell carcinoma. Cancer Res. 1994, 54, 2996-3000.
29. Baffa, R.; Negrini, M.; Mandes, B.; Rugge, M.; Ranzani, G. N.; Hirohashi, S.; Croce, C. M. Loss of heterozygosity for chromosome 11 in adenocarcinoma of the stomach. Cancer Res. 1996, 56, 268-272.
30. Soejima, H.; Nakagawachi, T.; Zhao, W.; Higashimoto, K.; Urano, T.; Matsukura, S.; Kitajima, Y.; Takeuchi, M.; Nakayama, M.; Oshimura, M.; Miyazaki, K.; Joh, K.; Mukai, T. Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer. Oncogene 2004, 23, 4380-4388.
31. Serrano, M.; Hannon, G. J.; Beach, D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993, 366, 704-707.
32. Pomerantz, J.; Schreiber-Agus, N.; Liegeois, N. J.; Silverman, A.; Alland, L.; Chin, L.; Potes, J.; Chen, K.; Orlow, I.; Lee, H. W.; Cordon-Cardo, C.; DePinho, R. A. The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 1998, 92, 713-723.
33. Serrano, M.; Lin, A. W.; McCurrach, M. E.; Beach, D.; Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997, 88, 593-602.
34. Palmero, I.; Pantoja, C.; Serrano, M. p19ARF links the tumour suppressor p53 to Ras. Nature 1998, 395, 125-126.
35. Bates, S.; Phillips, A. C.; Clark, P. A.; Stott, F.; Peters, G.; Ludwig, R. L.; Vousden, K. H. p14ARF links the tumour suppressors RB and p53. Nature 1998, 395, 124-125.
36. Hannon, G. J.; Beach, D. p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 1994, 371, 257-261.
37. Sherr, C. J. Cancer cell cycles. Science 1996, 274, 1672-1677.
38. Eads, C. A.; Lord, R. V.; Kurumboor, S. K.; Wickramasinghe, K.; Skinner, M. L.; Long, T. I.; Peters, J. H.; DeMeester, T. R.; Danenberg, K. D.; Danenberg, P. V.; Laird, P. W.; Skinner, K. A. Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. Cancer Res. 2000, 60, 5021-5026.
39. Bian, Y. S.; Osterheld, M. C.; Fontolliet, C.; Bosman, F. T.; Benhattar, J. p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus. Gastroenterology 2002, 122, 1113-1121.
40. Hardie, L. J.; Darnton, S. J.; Wallis, Y. L.; Chauhan, A.; Hainaut, P.; Wild, C. P.; Casson, A. G. p16 expression in Barrett's esophagus and esophageal adenocarcinoma: association with genetic and epigenetic alterations. Cancer Lett. 2005, 217, 221-230.
41. Wong, D. J.; Barrett, M. T.; Stoger, R.; Emond, M. J.; Reid, B. J. p16INK4a promoter is hypermethylated at a high frequency in esophageal adenocarcinomas. Cancer Res. 1997, 57, 2619-2622.
42. Klump, B.; Hsieh, C. J.; Holzmann, K.; Gregor, M.; Porschen, R. Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus. Gastroenterology 1998, 115, 1381-1386.
43. Sarbia, M.; Geddert, H.; Klump, B.; Kiel, S.; Iskender, E.; Gabbert, H. E. Hypermethylation of tumor suppressor genes (p16INK4A, p14ARF and APC) in adenocarcinomas of the upper gastrointestinal tract. Int. J. Cancer 2004, 111, 224-228.
44. Maesawa, C.; Tamura, G.; Nishizuka, S.; Ogasawara, S.; Ishida, K.; Terashima, M.; Sakata, K.; Sato, N.; Saito, K.; Satodate, R. Inactivation of the CDKN2 gene by homozygous deletion and de novo methylation is associated with advanced stage esophageal squamous cell carcinoma. Cancer Res. 1996, 56, 3875-3878.
45. Kwong, F. M.; Tang, J. C.; Srivastava, G.; Lung, M. L. Inactivation mechanisms and growth suppressive effects of p16INK4a in Asian esophageal squamous carcinoma cell lines. Cancer Lett. 2004, 208, 207-213.
46. Xing, E. P.; Nie, Y.; Wang, L. D.; Yang, G. Y.; Yang, C. S. Aberrant methylation of p16INK4a and deletion of p15INK4b are frequent events in human esophageal cancer in Linxian, China. Carcinogenesis 1999, 20, 77-84.
47. Xing, E. P.; Nie, Y.; Song, Y.; Yang, G. Y.; Cai, Y. C.; Wang, L. D.; Yang, C. S. Mechanisms of inactivation of p14ARF, p15INK4b, and p16INK4a genes in human esophageal squamous cell carcinoma. Clin. Cancer Res. 1999, 5, 2704-2713.
48. Fukuoka, T.; Hibi, K.; Nakao, A. Aberrant methylation is frequently observed in advanced esophageal squamous cell carcinoma. Anticancer Res. 2006, 26, 3333-3335.
49. Wang, J.; Sasco, A. J.; Fu, C.; Xue, H.; Guo, G.; Hua, Z.; Zhaou, Q.; Jiang, Q.; Xu, B. Aberrant DNA methylation of p16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphiam in esophageal squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 2008, 17, 118-125.
50. Nie, Y.; Liao, J.; Zhao, X.; Song, Y.; Yang, G. Y.; Wang, L. D.; Yang, C. S. Detection of multiple gene hypermethylation in the development of esophageal squamous cell carcinoma. Carcinogenesis 2002, 23, 1713-1720.
51. Abbaszadegan, M. R.; Raziee, H. R.; Ghafarzadegan, K.; Shakeri, M. T.; Afsharnezhad, S.; Ghavamnasiry, M. R. Aberrant p16 methylation, a possible epigenetic risk factor in familial esophageal squamous cell carcinoma. Int. J. Gastrointest. Cancer 2005, 36, 47-54.
52. Hibi, K.; Taguchi, M.; Nakayama, H.; Takase, T.; Kasai, Y.; Ito, K.; Akiyama, S.; Nakao, A. Molecular detection of p16 promoter methylation in the serum of patients with esophageal squamous cell carcinoma. Clin. Cancer Res. 2001, 7, 3135-3138.
53. Huebner, K. Tumor suppressors on 3p: a neoclassic quartet. Proc. Natl. Acad. Sci. USA 2001, 98, 14763-14765.
54. Lerman, M. I.; Minna, J. D. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res. 2000, 60, 6116-6133.
55. Ohta, M.; Inoue, H.; Cotticelli, M. G.; Kastury, K.; Baffa, R.; Palazzo, J.; Siprashvili, Z.; Mori, M.; McCue, P.; Druck, T.; Croce, C. M.; Huebner, K. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3,8) breakpoint, is abnormal in digestive tract cancers. Cell 1996, 84, 587-597.
56. de The, H.; Vivanco-Ruiz, M. M.; Tiollais, P.; Stunnenberg, H.; Dejean, A. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature 1990, 343, 177-180.
57. Dammann, R.; Li, C.; Yoon, J. H.; Chin, P. L.; Bates, S.; Pfeifer, G. P. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat. Genet. 2000, 25, 315-319.
58. Latif, F.; Tory, K.; Gnarra, J.; Yao, M.; Duh, F. M.; Orcutt, M. L.; Stackhouse, T.; Kuzmin, I.; Modi, W.; Geil, L.; Schmidt, L.; Zhou, F.; Li, H.; Wei, M. H.; Chen, F.; Glenn, G.; Choyke, P.; Walther, M. M.; Weng, Y.; Duan, D. R.; Dean, M.; Glavac, D.; Richards, F. M.; Crossey, P. A.; Ferguson-Smith, M. A.; Le Paslier, D.; Chumakov, L.; Cohen, D.; Chinault, A. C.; Maher, E. R.; Linehan, W. M.; Zbar, B.; Lerman, M. I. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993, 260, 1317-1320.
59. Siprashvili, Z.; Sozzi, G.; Barnes, L. D.; McCue, P.; Robinson, A. K.; Eryomin, V.; Sard, L.; Tagliabue, E.; Greco, A.; Fusetti, L.; Schwartz, G.; Pierotti, M. A.; Croce, C. M.; Huebner, K. Replacement of Fhit in cancer cells suppresses tumorigenicity. Proc. Natl. Acad. Sci. USA 1997, 94, 13771-13776.
60. Zou, T. T.; Lei, J.; Shi, Y. Q.; Yin, J.; Wang, S.; Souza, R. F.; Kong, D.; Shimada, Y.; Smolinski, K. N.; Greenwald, B. D.; Abraham, J. M.; Harpaz, N.; Meltzer, S. J. FHIT gene alterations in esophageal cancer and ulcerative colitis (UC). Oncogene 1997, 15, 101-105.
61. Schildhaus, H. U.; Krockel, I.; Lippert, H.; Malfertheiner, P.; Roessner, A.; Schneider-Stock, R. Promoter hypermethylation of p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in adenocarcinomas of the esophagus, esophagogastric junction and proximal stomach. Int. J. Oncol. 2005, 26, 1493-1500.
62. Clement, G.; Braunschweig, R.; Pasquier, N.; Bosman, F. T.; Benhattar, J. Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish Barrett's oesophagus patients at risk for malignant transformation. J. Pathol. 2006, 208, 100-107.
63. Tanaka, H.; Shimada, Y.; Harada, H.; Shinoda, M.; Hatooka, S.; Imamura, M.; Ishizaki, K. Methylation of the 5′ CpG island of the FHIT gene is closely associated with transcriptional inactivation in esophageal squamous cell carcinomas. Cancer Res. 1998, 58, 3429-3434.
64. Kuroki, T.; Trapasso, F.; Yendamuri, S.; Matsuyama, A.; Alder, H.; Mori, M.; Croce, C. M. Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma. Cancer Res. 2003, 63, 3724-3728.
65. Lee, E. J.; Lee, B. B.; Kim, J. W.; Shim, Y. M.; Hoseok, I.; Han, J.; Cho, E. Y.; Park, J.; Kim. D.H. Aberrant methylation of Fragile Histidine Triad gene is associated with poor prognosis in early stage esophageal squamous cell carcinoma. Eur. J. Cancer 2006, 42, 972-980.
66. Tzao, C.; Sun, G. H.; Tung, H. J.; Hsu, H. S.; Hsu, W. H.; Wang, Y. C.; Cheng, Y. L.; Lee, S. C. Reduced acetylated histone H4 is associated with promoter methylation of the fragile histidine triad gene in resected esophageal squamous cell carcinoma. Ann. Thorac. Surg. 2006, 82, 396-401; discussion 401.
67. Soma, T.; Kaganoi, J.; Kawabe, A.; Kondo, K.; Imamura, M.; Shimada, Y. Nicotine induces the fragile histidine triad methylation in human esophageal squamous epithelial cells. Int. J. Cancer 2006, 119, 1023-1027.
68. Morriss-Kay, G. M.; Ward, S. J. Retinoids and mammalian development. Int. Rev. Cytol.1999, 188, 73-131.
69. Dilworth, F. J.; Chambon, P. Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription. Oncogene 2001, 20, 3047-3054.
70. Touma, S. E.; Goldberg, J. S.; Moench, P.; Guo, X.; Tickoo, S. K.; Gudas, L. J.; Nanus, D. M. Retinoic acid and the histone deacetylase inhibitor trichostatin a inhibit the proliferation of human renal cell carcinoma in a xenograft tumor model. Clin. Cancer Res. 2005, 11, 3558-3566.
71. Hayashi, K.; Yokozaki, H.; Goodison, S.; Oue, N.; Suzuki, T.; Lotan, R.; Yasui, W.; Tahara, E. Inactivation of retinoic acid receptor beta by promoter CpG hypermethylation in gastric cancer. Differentiation 2001, 68, 13-21.
72. Wang, Y.; Fang, M. Z.; Liao, J.; Yang, G. Y.; Nie, Y.; Song, Y.; So, C.; Xu, X.; Wang, L. D.; Yang, C. S. Hypermethylation-associated inactivation of retinoic acid receptor beta in human esophageal squamous cell carcinoma. Clin. Cancer Res. 2003, 9, 5257-5263.
73. Liu, Z.; Zhang, L.; Ding, F.; Li, J.; Guo, M.; Li, W.; Wang, Y.; Yu, Z.; Zhan, Q.; Wu, M.; Liu, Z. 5-Aza-2′-deoxycytidine induces retinoic acid receptor-beta(2) demethylation and growth inhibition in esophageal squamous carcinoma cells. Cancer Lett. 2005, 230, 271-283.
74. Liu, Z. M.; Ding, F.; Guo, M. Z.; Zhang, L. Y.; Wu, M.; Liu, Z. H. Downregulation of retinoic acid receptor-beta(2) expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines. World J. Gastroenterol. 2004, 10, 771-775.
75. Wong, M. L.; Tao, Q.; Fu, L.; Wong, K. Y.; Qiu, G. H.; Law, F. B.; Tin, P. C.; Cheung, W. L.; Lee, P. Y.; Tang, J. C.; Tsao, G. S.; Lam, K. Y.; Law, S.; Wong, J.; Srivastava, G. Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma. Int. J. Oncol. 2006, 28, 767-773.
76. Yamaguchi, S.; Kato, H.; Miyazaki, T.; Sohda, M.; Kimura, H.; Ide, M.; Asao, T.; Kuwano, H. RASSF1A gene promoter methylation in esophageal cancer specimens. Dis. Esophagus 2005, 18, 253-256.
77. Kuroki, T.; Trapasso, F.; Yendamuri, S.; Matsuyama, A.; Alder, H.; Mori, M.; Croce, C. M. Promoter hypermethylation of RASSF1A in esophageal squamous cell carcinoma. Clin. Cancer Res. 2003, 9, 1441-1445.
78. Liu, L.; Gerson, S. L. Targeted modulation of MGMT: clinical implications. Clin. Cancer Res. 2006, 12, 328-331.
79. Baumann, S.; Keller, G.; Puhringer, F.; Napieralski, R.; Feith, M.; Langer, R.; Hofler, H.; Stein, H. J.; Sarbia, M. The prognostic impact of O6-Methylguanine-DNA Methyltransferase (MGMT) promotor hypermethylation in esophageal adenocarcinoma. Int. J. Cancer 2006, 119, 264-268.
80. Fang, M. Z.; Jin, Z.; Wang, Y.; Liao, J.; Yang, G. Y.; Wang, L. D.; Yang, C. S. Promoter hypermethylation and inactivation of O(6)-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines. Int. J. Oncol. 2005, 26, 615-622.
81. Pors, K.; Patterson, L. H. DNA mismatch repair deficiency, resistance to cancer chemotherapy and the development of hypersensitive agents. Curr. Top. Med. Chem. 2005, 5, 1133-1149.
82. Meltzer, S. J.; Yin, J.; Manin, B.; Rhyu, M. G.; Cottrell, J.; Hudson, E.; Redd, J. L.; Krasna, M. J.; Abraham, J. M.; Reid, B. J. Microsatellite instability occurs frequently and in both diploid and aneuploid cell populations of Barrett's-associated esophageal adenocarcinomas. Cancer Res. 1994, 54, 3379-3382.
83. Kulke, M. H.; Thakore, K. S.; Thomas, G.; Wang, H.; Loda M.; Eng, C.; Odze, R. D. Microsatellite instability and hMLH1/hMSH2 expression in Barrett esophagus-associated adenocarcinoma. Cancer 2001, 91, 1451-1457.
84. Tzao, C.; Hsu, H. S.; Sun, G. H.; Lai, H. L.; Wang, Y. C.; Tung, H. J.; Yu, C. P.; Cheng, Y. L.; Lee, S. C. Promoter methylation of the hMLH1 gene and protein expression of human mutL homolog 1 and human mutS homolog 2 in resected esophageal squamous cell carcinoma. J. Thorac. Cardiovasc. Surg. 2005, 130, 1371.
85. Zhang, G. Y.; Ma, C. X.; Liu, Q. L.; Le, X. P.; Ding, Y.; Zhang, Q. X. [Detection of methylation of hMSH2 gene promoter region of esophageal cancer]. Zhonghua Zhong Liu Za Zhi 2005, 27, 541-543.
86. Takayama, T.; Miyanishi, K.; Hayashi, T.; Sato, Y.; Niitsu, Y. Colorectal cancer: genetics of development and metastasis. J. Gastroenterol. 2006, 41, 185-192.
87. Clement, G.; Braunschweig, R.; Pasquier, N.; Bosman, F. T.; Benhattar, J. Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus. Oncogene 2006, 25, 3084-3092.
88. Powell, S. M.; Papadopoulos, N.; Kinzler, K. W.; Smolinski, K. N.; Meltzer, S. J. APC gene mutations in the mutation cluster region are rare in esophageal cancers. Gastroenterology 1994, 107, 1759-1763.
89. Takeichi, M. Morphogenetic roles of classic cadherins. Curr. Opin. Cell Biol. 1995, 7, 619-627.
90. Katagiri, A.; Watanabe, R.; Tomita, Y. E-cadherin expression in renal cell cancer and its significance in metastasis and survival. Br. J. Cancer 1995, 71, 376-379.
91. Corn, P. G.; Heath, E. I.; Heitmiller, R.; Fogt, F.; Forastiere, A. A.; Herman, J. G.; Wu, T. T. Frequent hypermethylation of the 5′ CpG island of E-cadherin in esophageal adenocarcinoma. Clin. Cancer Res. 2001, 7, 2765-2769.
92. Si, H. X.; Tsao, S. W.; Lam, K. Y.; Srivastava, G.; Liu, Y.; Wong, Y. C.; Shen, Z. Y.; Cheung, A. L. E-cadherin expression is commonly downregulated by CpG island hypermethylation in esophageal carcinoma cells. Cancer Lett. 2001, 173, 71-78.
93. Takeno, S.; Noguchi, T.; Fumoto, S.; Kimura, Y.; Shibata, T.; Kawahara, K. E-cadherin expression in patients with esophageal squamous cell carcinoma: promoter hypermethylation, Snail overexpression, and clinicopathologic implications. Am. J. Clin. Pathol. 2004, 122, 78-84.
94. Bian, J.; Wang, Y.; Smith, M. R.; Kim, H.; Jacobs, C.; Jackman, J.; Kung, H. F.; Colburn, N. H.; Sun, Y. Suppression of in vivo tumor growth and induction of suspension cell death by tissue inhibitor of metalloproteinases (TIMP)-3. Carcinogenesis 1996, 17, 1805-1811.
95. Baker, A. H.; George, S. J.; Zaltsman, A. B.; Murphy, G.; Newby, A. C. Inhibition of invasion and induction of apoptotic cell death of cancer cell lines by overexpression of TIMP-3. Br. J. Cancer 1999, 79, 1347-1355.
96. Darnton, S. J.; Hardie, L. J.; Muc R. S.; Wild, C. P.; Casson, A. G. Tissue inhibitor of metalloproteinase-3 (TIMP-3) gene is methylated in the development of esophageal adenocarcinoma: loss of expression correlates with poor prognosis. Int. J. Cancer 2005, 115, 351-358.
97. Bialik, S.; Kimchi, A. DAP-kinase as a target for drug design in cancer and diseases associated with accelerated cell death. Semin. Cancer Biol. 2004, 14, 283-294.
98. Kuester, D.; Dar, A. A.; Moskaluk, C. C.; Krueger, S.; Meyer, F.; Hartig, R.; Stolte, M.; Malfertheiner, P.; Lippert, H.; Roessner, A.; El-Rifai, W.; Schneider-Stock, R. Early involvement of death-associated protein kinase promoter hypermethylation in the carcinogenesis of Barrett's esophageal adenocarcinoma and its association with clinical progression. Neoplasia 2007, 9, 236-245.
99. Bae, S. C.; Choi, J. K. Tumor suppressor activity of RUNX3. Oncogene 2004, 23, 4336-4340.
100. Li, Q. L.; Ito, K.; Sakakura, C.; Fukamachi, H.; Inoue, K.; Chi, X. Z.; Lee, K. Y.; Nomura, S.; Lee, C. W.; Han, S. B.; Kim, H. M.; Kim, W. J.; Yamamoto, H.; Yamashita, N.; Yano, T.; Ikeda, T.; Itohara, S.; Inazawa, J.; Abe, T.; Hagiwara, A.; Yamagishi, H.; Ooe, A.; Kaneda, A.; Sugimura, T.; Ushijima, T.; Bae, S. C.; Ito, Y. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 2002, 109, 113-124.
101. Schulmann, K.; Sterian, A.; Berki, A.; Yin, J.; Sato, F.; Xu, Y.; Olaru, A.; Wang, S.; Mori, Y.; Deacu, E.; Hamilton, J.; Kan, T.; Krasna, M. J.; Beer, D. G.; Pepe, M. S.; Abraham, J. M.; Feng, Z.; Schmiegel, W.; Greenwald, B. D.; Meltzer, S. J. Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk. Oncogene 2005, 24, 4138-4148.
102. Sakakura, C.; Miyagawa, K.; Fukuda, K. I.; Nakashima, S.; Yoshikawa, T.; Kin, S.; Nakase, Y.; Ida, H.; Yazumi, S.; Yamagishi, H.; Okanoue, T.; Chiba, T.; Ito, K.; Hagiwara, A.; Ito, Y. Frequent silencing of RUNX3 in esophageal squamous cell carcinomas is associated with radioresistance and poor prognosis. Oncogene 2007, 26, 5927-5938.
103. Logan, C. Y.; Nusse, R. The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol. 2004, 20, 781-810.
104. Zou, H.; Molina, J. R.; Harrington, J. J.; Osborn, N. K.; Klatt, K. K.; Romero, Y.; Burgart, L. J.; Ahlquist, D. A. Aberrant methylation of secreted frizzled-related protein genes in esophageal adenocarcinoma and Barrett's esophagus. Int. J. Cancer 2005, 116, 584-591.
105. Kim, M. S.; Yamashita, K.; Baek, J. H.; Park, H. L.; Carvalho, A. L.; Osada, M.; Hoque, M. O.; Upadhyay, S.; Mori, M.; Moon, C.; Sidransky, D. N-methyl-D-aspartate receptor type 2B is epigenetically inactivated and exhibits tumor-suppressive activity in human esophageal cancer. Cancer Res. 2006, 66, 3409-3418.
106. Yue, C. M.; Deng, D. J.; Bi, M. X.; Guo, L. P; Lu, S. H. Expression of ECRG4, a novel esophageal cancer-related gene, downregulated by CpG island hypermethylation in human esophageal squamous cell carcinoma. World J. Gastroenterol. 2003, 9, 1174-1178.
107. Roth, M. J.; Abnet, C. C.; Hu, N.; Wang, Q. H.; Wei, W.Q.; Green, L.; D'Alelio, M.; Qiao, Y. L.; Dawsey, S. M.; Taylor, P. R.; Woodson, K. p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in esophageal squamous cell carcinoma and its precursor lesions. Oncol. Rep. 2006, 15, 1591-1597.
108. Smith, E.; Drew, P. A.; Tian, Z. Q.; De Young, N. J.; Liu, J. F.; Mayne, G. C.; Ruszkiewicz, A. R.; Watson, D. I.; Jamieson, G. G. Metallothionien 3 expression is frequently down-regulated in oesophageal squamous cell carcinoma by DNA methylation. Mol. Cancer 2005, 4, 42.
109. Guo, M.; House, M. G.; Akiyama, Y.; Qi, Y.; Capagna, D.; Harmon, J.; Baylin, S. B.; Brock, M. V.; Herman, J. G. Hypermethylation of the GATA gene family in esophageal cancer. Int. J Cancer 2006, 119, 2078-2083.
110. Seng, T. J.; Low, J. S.; Li, H.; Cui, Y.; Goh, H. K.; Wong, M. L.; Srivastava, G.; Sidransky, D.; Califano, J.; Steenbergen, R. D.; Rha, S.Y.; Tan, J.; Hsieh, W. S.; Ambinder, R. F.; Lin, X.; Chan, A. T.; Tao, Q. The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation. Oncogene 2007, 26, 934-944.
111. Yamashita, K.; Mimori, K.; Inoue, H.; Mori, M.; Sidransky, D. A tumor-suppressive role for trypsin in human cancer progression. Cancer Res. 2003, 63, 6575-6578.
112. Jin, Z.; Olaru, A.; Yang, J.; Sato, F.; Cheng, Y.; Kan, T.; Mori, Y.; Mantzur, C.; Paun, B.; Hamilton, J. P.; Ito, T.; Wang, S.; David, S.; Agarwal, R.; Beer, D. G.; Abraham, J. M.; Meltzer, S. J. Hypermethylation of tachykinin-1 is a potential biomarker in human esophageal cancer. Clin. Cancer Res. 2007, 13, 6293-6300.
113. Lo, P. H.; Leung, A. C.; Kwok, C. Y.; Cheung, W. S.; Ko, J. M.; Yang, L. C.; Law, S.; Wang, L. D.; Li, J.; Stanbridge, E. J.; Srivastava, G.; Tang, J. C.; Tsao, S. W.; Lung, M. L. Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene 2007, 26, 148-157.
114. Nie, Y.; Yang, G.; Song, Y.; Zhao, X.; So, C.; Liao, J.; Wang, L. D.; Yang, C. S. DNA hypermethylation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomas. Carcinogenesis 2001, 22, 1615-1623.
115. Ying, J.; Li, H.; Seng, T. J.; Langford, C.; Srivastava, G.; Tsao, S. W.; Putti, T.; Murray, P.; Chan, A. T.; Tao, Q. Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene 2006, 25, 1070-1080.
116. Chan, S. L.; Cui, Y.; van Hasselt, A.; Li, H.; Srivastava, G.; Jin, H.; Ng, K. M.; Wang, Y.; Lee, K. Y.; Tsao, G. S.; Zhong, S.; Robertson, K. D.; Rha, S. Y.; Chan, A. T.; Tao, Q. The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas. Lab. Invest. 2007, 87, 644-650.
117. Mizuiri, H.; Yoshida, K.; Toge, T.; Oue, N.; Aung, P.P.; Noguchi, T.; Yasui, W. DNA methylation of genes linked to retinoid signaling in squamous cell carcinoma of the esophagus: DNA methylation of CRBP1 and TIG1 is associated with tumor stage. Cancer Sci. 2005, 96, 571-577.
118. Shibata, Y.; Haruki, N.; Kuwabara, Y.; Ishiguro, H.; Shinoda, N.; Sato, A.; Kimura, M.; Koyama, H.; Toyama, T.; Nishiwaki, T.; Kudo, J.; Terashita, Y.; Konishi, S.; Sugiura, H.; Fujii, Y. Chfr expression is downregulated by CpG island hypermethylation in esophageal cancer. Carcinogenesis 2002, 23, 1695-1699.
119. Sonoda, I.; Imoto, I.; Inoue, J.; Shibata, T.; Shimada, Y.; Chin, K.; Imamura, M.; Amagasa, T.; Gray, J. W.; Hirohashi, S.; Inazawa, J. Frequent silencing of low density lipoprotein receptor-related protein 1B (LRP1B) expression by genetic and epigenetic mechanisms in esophageal squamous cell carcinoma. Cancer Res. 2004, 64, 3741-3747.
120. Hibi, K.; Kodera, Y.; Ito, K.; Akiyama, S.; Nakao, A. Methylation pattern of CDH13 gene in digestive tract cancers. Br. J. Cancer 2004, 91, 1139-1142.
121. Ito, T.; Shimada, Y.; Hashimoto, Y.; Kaganoi, J.; Kan, T.; Watanabe, G.; Murakami, Y.; Imamura, M. Involvement of TSLC1 in progression of esophageal squamous cell carcinoma. Cancer Res. 2003, 63, 6320-6326.
122. Yi Lo, P. H.; Chung Leung, A. C.; Xiong, W.; Law, S.; Duh, F. M.; Lerman, M. I.; Stanbridge, E. J.; Lung, M. L. Expression of candidate chromosome 3p21.3 tumor suppressor genes and downregulation of BLU in some esophageal squamous cell carcinomas. Cancer Lett. 2006, 234, 184-192.
123. Lee, O. J.; Schneider-Stock, R.; McChesney, P. A.; Kuester, D.; Roessner, A.; Vieth, M.; Moskaluk, C. A.; El-Rifai, W. Hypermethylation and loss of expression of glutathione peroxidase-3 in Barrett's tumorigenesis. Neoplasia 2005, 7, 854-861.
124. Onwuegbusi, B. A.; Aitchison, A.; Chin, S. F.; Kranjac, T.; Mills, I.; Huang, Y.; Lao-Sirieix, P.; Caldas, C.; Fitzgerald, R. C. Impaired transforming growth factor beta signalling in Barrett's carcinogenesis due to frequent SMAD4 inactivation. Gut 2006, 55, 764-774.
125. Hamilton, J.P.; Sato, F.; Jin, Z.; Greenwald, B. D.; Ito, T.; Mori, Y.; Paun, B. C.; Kan, T.; Cheng, Y.; Wang, S.; Yang, J.; Abraham, J. M.; Meltzer, S. J. Reprimo methylation is a potential biomarker of Barrett's-Associated esophageal neoplastic progression. Clin. Cancer Res. 2006, 12, 6637-6642.
126. Jin, Z.; Mori, Y.; Yang, J.; Sato, F.; Ito, T.; Cheng, Y.; Paun, B.; Hamilton, J. P.; Kan, T.; Olaru, A.; David, S.; Agarwal, R.; Abraham, J. M.; Beer, D.; Montgomery, E.; Meltzer, S. J. Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma. Oncogene 2007, 26, 6332-6340.
127. Costello, J. F.; Fruhwald, M. C.; Smiraglia, D.J.; Rush, L. J.; Robertson, G. P.; Gao, X.; Wright, F. A.; Feramisco, J. D.; Peltomaki, P.; Lang, J. C.; Schuller, D. E.; Yu, L.; Bloomfield, C. D.; Caligiuri, M. A.; Yates, A.; Nishikawa, R.; Su Huang, H.; Petrelli, N. J.; Zhang, X.; O'Dorisio, M. S.; Held, W. A.; Cavenee, W. K.; Plass, C. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat. Genet. 2000, 24, 132-138.
128. Toyota, M.; Ahuja, N.; Ohe-Toyota, M.; Herman, J. G.; Baylin, S. B.; Issa, J. P. CpG island methylator phenotype in colorectal cancer. Proc. Natl. Acad. Sci. USA 1999, 96, 8681-8686.
129. Eads, C. A.; Lord, R. V.; Wickramasinghe, K.; Long, T. I.; Kurumboor, S. K.; Bernstein, L.; Peters, J. H.; DeMeester, S. R.; DeMeester, T. R.; Skinner, K. A.; Laird, P. W. Epigenetic patterns in the progression of esophageal adenocarcinoma. Cancer Res. 2001, 61, 3410-3418.
130. Brock, M. V.; Gou, M.; Akiyama, Y.; Muller, A.; Wu, T. T.; Montgomery, E.; Deasel, M.; Germonpre, P.; Rubinson, L.; Heitmiller, R. F.; Yang, S. C.; Forastiere, A. A.; Baylin, S. B.; Herman, J. G. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin. Cancer Res. 2003, 9, 2912-2919.
131. Toh, Y.; Yamamoto, M.; Endo, K.; Ikeda, Y.; Baba, H.; Kohnoe, S.; Yonemasu, H.; Hachitanda, Y.; Okamura, T.; Sugimachi, K. Histone H4 acetylation and histone deacetylase 1 expression in esophageal squamous cell carcinoma. Oncol. Rep. 2003, 10, 333-338.
132. Toh, Y.; Ohga, T.; Endo, K.; Adachi, E.; Kusumoto, H.; Haraguchi, M.; Okamura, T.; Nicolson, G.L. Expression of the metastasis-associated metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas. Int. J. Cancer 2004, 110, 362-367.
133. Samani, A. A.; Yakar, S.; LeRoith, D.; Brodt, P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr. Rev. 2007, 28, 20-47.
134. Cui, H.; Cruz-Correa, M.; Giardiello, F. M.; Hutcheon, D. F.; Kafonek, D. R.; Brandenburg, S.; Wu, Y.; He, X.; Powe, N. R.; Feinberg, A. P. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 2003, 299, 1753-1755.
135. Cui, H.; Horon, I. L.; Ohlsson, R.; Hamilton, S. R.; Feinberg, A. P. Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nat. Med. 1998, 4, 1276-1280.
136. Feagins, L. A.; Susnow, N.; Zhang, H. Y.; Pearson, S.; Owen, C.; Schmalstieg, W. F.; Terada, L. S.; Spechler, S. J.; Ramirez, R. D.; Souza, R. F. Gain of allelic gene expression for IGF-II occurs frequently in Barrett's esophagus. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 290, G871-G875.
137. Mori, M.; Inoue, H.; Shiraishi, T.; Mimori, K.; Shibuta, K.; Nakashima, H.; Mafune, K.; Tanaka, Y.; Ueo, H.; Barnard, G. F.; Sugimachi, K.; Akiyoshi, T. Relaxation of insulin-like growth factor 2 gene imprinting in esophageal cancer. Int. J. Cancer 1996, 68, 441-446.
138. Xu, W.; Fan, H.; He, X.; Zhang, J.; Xie, W. LOI of IGF2 is associated with esophageal cancer and linked to methylation status of IGF2 DMR. J. Exp. Clin. Cancer Res. 2006, 25, 543-547.
139. Kaghad, M.; Bonnet, H.; Yang, A.; Creancier, L.; Biscan, J. C.; Valent, A.; Minty, A.; Chalon, P.; Lelias, J. M.; Dumont, X.; Ferrara, P.; McKeon, F.; Caput, D. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 1997, 90, 809-819.
140. Prabhu, N. S.; Somasundaram, K.; Satyamoorthy, K.; Herlyn, M.; El-Deiry, W. S. p73beta, unlike p53, suppresses growth and induces apoptosis of human papillomavirus E6-expressing cancer cells. Int. J. Oncol. 1998, 13, 5-9.
141. Mai, M.; Yokomizo, A.; Qian, C.; Yang, P.; Tindall, D. J.; Smith, D. I.; Liu, W. Activation of p73 silent allele in lung cancer. Cancer Res. 1998, 58, 2347-2349.
142. Mai, M.; Qian, C.; Yokomizo, A.; Tindall, D. J.; Bostwick, D.; Polychronakos, C.; Smith, D. I.; Liu, W. Loss of imprinting and allele switching of p73 in renal cell carcinoma. Oncogene 1998, 17, 1739-1741.
143. Cai, Y. C.; Yang, G. Y.; Nie, Y.; Wang, L. D.; Zhao, X.; Song, Y. L.; Seril, D. N.; Liao, J.; Xing, E. P.; Yang, C. S. Molecular alterations of p73 in human esophageal squamous cell carcinomas: loss of heterozygosity occurs frequently, loss of imprinting and elevation of p73 expression may be related to defective p53. Carcinogenesis 2000, 21, 683-689.
144. Steenman, M. J.; Rainier, S.; Dobry, C. J.; Grundy, P.; Horon, I. L.; Feinberg, A. P. Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour. Nat. Genet. 1994, 7, 433-439.
145. Moulton, T.; Crenshaw, T.; Hao, Y.; Moosikasuwan, J.; Lin, N.; Dembitzer, F.; Hensle, T.; Weiss, L.; McMorrow, L.; Loew, T. Epigenetic lesions at the H19 locus in Wilms' tumour patients. Nat. Genet. 1994, 7, 440-447.
146. Hibi, K.; Nakamura, H.; Hirai, A.; Fujikake, Y.; Kasa,i Y.; Akiyama, S.; Ito, K.; Takagi, H. Loss of H19 imprinting in esophageal cancer. Cancer Res. 1996, 56, 480-482.
147. Egger, G.; Liang, G.; Aparicio, A.; Jones, P. A. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004, 429, 457-463.
148. Szyf, M. Therapeutic implications of DNA methylation. Future Oncol. 2005, 1, 125-135.
149. Lapeyre, J. N.; Becker, F. F. 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem. Biophys. Res. Commun. 1979, 87, 698-705.
150. Feinberg, A. P.; Vogelstein, B. Hypomethylation of ras oncogenes in primary human cancers. Biochem. Biophys. Res. Commun. 1983, 111, 47-54.
151. Gaudet, F.; Hodgson, J. G.; Eden, A.; Jackson-Grusby, L.; Dausman, J.; Gray, J. W.; Leonhardt, H.; Jaenisch, R. Induction of tumors in mice by genomic hypomethylation. Science 2003, 300, 489-492.
152. Toyota, M.; Issa, J. P. Epigenetic changes in solid and hematopoietic tumors. Semin. Oncol. 2005, 32, 521-530.
153. Laird, P. W.; Jackson-Grusby, L.; Fazeli, A.; Dickinson, S. L.; Jung, W. E.; Li, E.; Weinberg, R. A.; Jaenisch, R. Suppression of intestinal neoplasia by DNA hypomethylation. Cell 1995, 81, 197-205.
154. Belinsky, S. A.; Klinge, D. M.; Stidley, C. A.; Issa, J. P.; Herman, J. G.; March, T. H.; Baylin, S. B. Inhibition of DNA methylation and histone deacetylation prevents murine lung cancer. Cancer Res. 2003, 63, 7089-7093.
155. El-Osta, A. DNMT cooperativity - the developing links between methylation, chromatin structure and cancer. Bioessays 2003, 25, 1071-1084.
156. Rao, P. M.; Antony, A.; Rajalakshmi, S.; Sarma, D. S. Studies on hypomethylation of liver DNA during early stages of chemical carcinogenesis in rat liver. Carcinogenesis 1989, 10, 933-937.
157. Wainfan, E.; Poirier, L. A. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res. 1992, 52, 2071s-2077s.
158. Szyf, M.; Pakneshan, P.; Rabbani, S. A. DNA methylation and breast cancer. Biochem. Pharmacol. 2004, 68, 1187-1197.
159. Cui, H.; Onyango, P.; Brandenburg, S.; Wu, Y.; Hsieh, C. L.; Feinberg, A. P. Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res. 2002, 62, 6442-6446.
160. Issa, J. P. DNA methylation as a therapeutic target in cancer. Clin. Cancer Res. 2007, 13, 1634-1637.
161. Gowher, H.; Jeltsch, A. Mechanism of inhibition of DNA methyltransferases by cytidine analogs in cancer therapy. Cancer Biol. Ther. 2004, 3, 1062-1068.
162. Cornacchia, E.; Golbus, J.; Maybaum, J.; Strahler, J.; Hanash, S.; Richardson, B. Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol. 1988, 140, 2197-2200.
163. Chuang, J. C.; Yoo, C. B.; Kwan, J. M.; Li, T. W.; Liang, G.; Yang, A. S.; Jones, P. A. Comparison of biological effects of nonnucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine. Mol. Cancer Ther. 2005, 4, 1515-1520.
164. Fang, M. Z.; Wang, Y.; Ai, N.; Hou, Z.; Sun, Y.; Lu, H.; Welsh, W.; Yang, C. S. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 2003, 63, 7563-7570.
165. Dixon, R. A.; Ferreira, D. Genistein. Phytochemistry 2002, 60, 205-211.
166. Fang, M. Z.; Chen, D.; Sun, Y.; Jin, Z.; Christman, J. K.; Yang, C. S. Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy. Clin. Cancer Res. 2005, 11, 7033-7041.
167. Kassis, E. S.; Zhao, M.; Hong, J. A.; Chen, G. A.; Nguyen, D. M.; Schrump, D. S. Depletion of DNA methyltransferase 1 and/or DNA methyltransferase 3b mediates growth arrest and apoptosis in lung and esophageal cancer and malignant pleural mesothelioma cells. J. Thorac. Cardiovasc. Surg. 2006, 131, 298-306.
168. McLaughlin, F.; La Thangue, N. B. Histone deacetylase inhibitors open new doors in cancer therapy. Biochem. Pharmacol. 2004, 68, 1139-1144.
169. Blagosklonny, M. V.; Robey, R.; Sackett, D. L.; Du, L.; Traganos, F.; Darzynkiewicz, Z.; Fojo, T.; Bates, S. E. Histone deacetylase inhibitors all induce p21 but differentially cause tubulin acetylation, mitotic arrest, and cytotoxicity. Mol. Cancer Ther. 2002, 1, 937-941.
170. Chen, C. S.; Weng, S. C.; Tseng, P. H.; Lin, H. P.; Chen, C. S. Histone acetylation-independent effect of histone deacetylase inhibitors on Akt through the reshuffling of protein phosphatase 1 complexes. J. Biol. Chem. 2005, 280, 38879-38887.
171. Kelly, W. K.; Richon, V. M.; O'Connor, O.; Curley, T.; MacGregor-Curtelli, B.; Tong, W.; Klang, M.; Schwartz, L.; Richardson, S.; Rosa, E.; Drobnjak, M.; Cordon-Cordo, C.; Chiao, J. H.; Rifkind, R. Marks, P. A. Scher, H. Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin. Cancer Res. 2003, 9, 3578-3588.
172. 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, 3923-3931.
173. Maxhimer, J. B.; Reddy, R. M.; Zuo, J.; Cole, G. W.; Schrump, D. S.; Nguyen, D. M. Induction of apoptosis of lung and esophageal cancer cells treated with the combination of histone deacetylase inhibitor (trichostatin A) and protein kinase C inhibitor (calphostin C). J. Thorac. Cardiovasc. Surg. 2005, 129, 53-63.
174. Hoshino, I.; Matsubara, H.; Hanari, N.; Mori, M.; Nishimori, T.; Yoneyama, Y.; Akutsu, Y.; Sakata, H.; Matsushita, K.; Seki, N.; Ochiai, T. Histone deacetylase inhibitor FK228 activates tumor suppressor Prdx1 with apoptosis induction in esophageal cancer cells. Clin. Cancer Res. 2005, 11, 7945-7952.
175. Fang, X.; Zheng, C.; Liu, Z.; Ekman, P.; Xu, D. Enhanced sensitivity of prostate cancer DU145 cells to cisplatinum by 5-aza-2′-deoxycytidine. Oncol. Rep. 2004, 12, 523-526.
176. Kim, M. S.; Blake, M.; Baek, J. H.; Kohlhagen, G.; Pommier, Y.; Carrier, F. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res. 2003, 63, 7291-7300.