{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:31:14Z","timestamp":1792654274824,"version":"4.5.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,4,29]],"date-time":"2005-04-29T00:00:00Z","timestamp":1114732800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The antihypertensive compound hydralazine is a known demethylating agent. This phase I study evaluated the tolerability and its effects upon DNA methylation and gene reactivation in patients with untreated cervical cancer.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Hydralazine was administered to cohorts of 4 patients at the following dose levels: I) 50 mg\/day, II) 75 mg\/day, III) 100 mg\/day and IV) 150 mg\/day. Tumor biopsies and peripheral blood samples were taken the day before and after treatment. The genes APC, MGMT; ER, GSTP1, DAPK, RAR\u03b2, FHIT and p16 were evaluated pre and post-treatment for DNA promoter methylation and gene expression by MSP (Methylation-Specific PCR) and RT-PCR respectively in each of the tumor samples. Methylation of the imprinted H19 gene and the \"normally methylated\" sequence clone 1.2 was also analyzed. Global DNA methylation was analyzed by capillary electrophoresis and cytosine extension assay. Toxicity was evaluated using the NCI Common Toxicity Criteria.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Hydralazine was well tolerated. Toxicities were mild being the most common nausea, dizziness, fatigue, headache and palpitations. Overall, 70% of the pretreatment samples and all the patients had at least one methylated gene. Rates of demethylation at the different dose levels were as follows: 50 mg\/day, 40%; 75 mg\/day, 52%, 100 mg\/day, 43%, and 150 mg\/day, 32%. Gene expression analysis showed only 12 informative cases, of these 9 (75%) re-expressed the gene. There was neither change in the methylation status of H19 and clone 1.2 nor changes in global DNA methylation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Hydralazine at doses between 50 and 150 mg\/day is well tolerated and effective to demethylate and reactivate the expression of tumor suppressor genes without affecting global DNA methylation<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-5-44","type":"journal-article","created":{"date-parts":[[2005,5,3]],"date-time":"2005-05-03T18:24:57Z","timestamp":1115144697000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes"],"prefix":"10.1186","volume":"5","author":[{"given":"Pilar","family":"Zambrano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Segura-Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Perez-Cardenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucely","family":"Cetina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Revilla-Vazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Taja-Chayeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Chavez-Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Angeles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Sandoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Trejo-Becerril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Chanona-Vilchis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Duenas-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,4,29]]},"reference":[{"key":"232_CR1","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.1038\/sj.onc.1204341","volume":"20","author":"KD Robertson","year":"2001","unstructured":"Robertson KD: DNA methylation, methyltransferases and cancer. Oncogene. 2001, 20: 3139-55. 10.1038\/sj.onc.1204341.","journal-title":"Oncogene"},{"key":"232_CR2","doi-asserted-by":"publisher","first-page":"33002","DOI":"10.1074\/jbc.274.46.33002","volume":"274","author":"S Pradhan","year":"1999","unstructured":"Pradhan S, Bacolla A, Wells RD, Roberts RJ: Recombinant human DNA (cytosine-5) methyltransferase.I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem. 1999, 274: 33002-10. 10.1074\/jbc.274.46.33002.","journal-title":"J Biol Chem"},{"key":"232_CR3","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1101\/gad.9.19.2325","volume":"9","author":"C Beard","year":"1995","unstructured":"Beard C, Li E, Jaenisch R: methylation activates Xist in somatic but not in embryonic cells. Genes Dev. 1995, 9: 2325-34.","journal-title":"Genes Dev"},{"key":"232_CR4","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/366362a0","volume":"366","author":"E Li","year":"1993","unstructured":"Li E, Beard C, Jaenisch R: Role for DNA methylation in genomic imprinting. Nature. 1993, 366: 362-5. 10.1038\/366362a0.","journal-title":"Nature"},{"key":"232_CR5","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/0092-8674(92)90561-P","volume":"71","author":"H Leonhardt","year":"1992","unstructured":"Leonhardt H, Page AW, Weier HU, Bestor TH: A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell. 1992, 71: 865-73. 10.1016\/0092-8674(92)90561-P.","journal-title":"Cell"},{"key":"232_CR6","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1126\/science.277.5334.1996","volume":"277","author":"LS Chuang","year":"1997","unstructured":"Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF: Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for P21WAF1. Science. 1997, 277: 1996-2000. 10.1126\/science.277.5334.1996.","journal-title":"Science"},{"key":"232_CR7","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0092-8674(00)81656-6","volume":"99","author":"M Okano","year":"1999","unstructured":"Okano M, Bell DW, Haber DA, Li E: DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999, 99: 247-57. 10.1016\/S0092-8674(00)81656-6.","journal-title":"Cell"},{"key":"232_CR8","doi-asserted-by":"publisher","first-page":"2536","DOI":"10.1093\/nar\/26.11.2536","volume":"26","author":"M Okano","year":"1998","unstructured":"Okano M, Xie S, Li E: Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells. Nucleic Acids Res. 1998, 26: 2536-40. 10.1093\/nar\/26.11.2536.","journal-title":"Nucleic Acids Res"},{"key":"232_CR9","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/0959-437X(93)90027-M","volume":"3","author":"PH Tate","year":"1993","unstructured":"Tate PH, Bird AP: Effects of DNA methylation on DNA-binding proteins and gene expression. Curr Opin Genet Dev. 1993, 3: 226-31. 10.1016\/0959-437X(93)90027-M.","journal-title":"Curr Opin Genet Dev"},{"key":"232_CR10","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/S0092-8674(00)81887-5","volume":"88","author":"X Nan","year":"1997","unstructured":"Nan X, Campoy FJ, Bird A: MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997, 88: 471-81. 10.1016\/S0092-8674(00)81887-5.","journal-title":"Cell"},{"key":"232_CR11","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/77023","volume":"25","author":"MR Rountree","year":"2000","unstructured":"Rountree MR, Bachman KE, Baylin SB: DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nature Genet. 2000, 25: 269-77. 10.1038\/77023.","journal-title":"Nature Genet"},{"key":"232_CR12","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/30764","volume":"393","author":"X Nan","year":"1998","unstructured":"Nan X, Ng HH, Johnson CA, Turner BM, Eisenman RN, Bird A: Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998, 393: 386-9. 10.1038\/30764.","journal-title":"Nature"},{"key":"232_CR13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/0092-8674(92)90526-I","volume":"70","author":"A Bird","year":"1992","unstructured":"Bird A: The essentials of DNA methylation. Cell. 1992, 70: 5-8. 10.1016\/0092-8674(92)90526-I.","journal-title":"Cell"},{"key":"232_CR14","doi-asserted-by":"publisher","first-page":"5380","DOI":"10.1038\/sj.onc.1205598","volume":"21","author":"SJ Clark","year":"2002","unstructured":"Clark SJ, Melki J: DNA methylation and gene silencing in cancer: which is the guilty party?. Oncogene. 2002, 21: 5380-7. 10.1038\/sj.onc.1205598.","journal-title":"Oncogene"},{"key":"232_CR15","doi-asserted-by":"publisher","first-page":"11995","DOI":"10.1073\/pnas.90.24.11995","volume":"90","author":"F Antequera","year":"1993","unstructured":"Antequera F, Bird A: Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci USA. 1993, 90: 11995-9.","journal-title":"Proc Natl Acad Sci USA"},{"key":"232_CR16","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/S0168-9525(99)01971-X","volume":"16","author":"SB Baylin","year":"2000","unstructured":"Baylin SB, Herman JG: DNA hyper methylation in tumorigenesis: epigenetics joins genetics. Trends Genet. 2000, 16: 168-74. 10.1016\/S0168-9525(99)01971-X.","journal-title":"Trends Genet"},{"key":"232_CR17","doi-asserted-by":"publisher","first-page":"573","DOI":"10.7326\/0003-4819-134-7-200104030-00011","volume":"134","author":"V Santini","year":"2001","unstructured":"Santini V, Kantarjian HM, Issa JP: Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann Intern Med. 2001, 134: 573-86.","journal-title":"Ann Intern Med"},{"key":"232_CR18","doi-asserted-by":"publisher","first-page":"4594","DOI":"10.1074\/jbc.274.8.4594","volume":"274","author":"P Bigey","year":"1999","unstructured":"Bigey P, Knox JD, Croteau S, Bhattacharya SK, Theberge J, Szyf M: Modified oligonucleotides as bona fide antagonists of proteins interacting with DNA. Hairpin antagonists of the human DNA methyltransferase. J Biol Chem. 1999, 274: 4594-606. 10.1074\/jbc.274.8.4594.","journal-title":"J Biol Chem"},{"key":"232_CR19","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1093\/carcin\/20.2.343","volume":"20","author":"LE Lantry","year":"1999","unstructured":"Lantry LE, Zhang Z, Crist KA, Wang Y, Kelloff GJ, Lubet RA, You M: 5-Aza-2'-deoxycytidine is chemopreventive in a 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone-induced primary mouse lung tumor model. Carcinogenesis. 1999, 20: 343-6. 10.1093\/carcin\/20.2.343.","journal-title":"Carcinogenesis"},{"key":"232_CR20","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/0277-5379(85)90207-X","volume":"21","author":"JM Covey","year":"1985","unstructured":"Covey JM, Zaharko DS: Comparison of the in vitro cytotoxicity (L1210) of 5-aza-2'-deoxycytidine with its therapeutic and toxic effects in mice. Eur J Cancer Clin Oncol. 1985, 21: 109-117. 10.1016\/0277-5379(85)90207-X.","journal-title":"Eur J Cancer Clin Oncol"},{"key":"232_CR21","doi-asserted-by":"publisher","first-page":"8891","DOI":"10.1073\/pnas.90.19.8891","volume":"90","author":"J Wu","year":"1993","unstructured":"Wu J, Issa JP, Herman J, Bassett DE, Nelking BD, Baylin SB: Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH3T3 cells. Proc Natl Acad Sci USA. 1993, 90: 8891-5.","journal-title":"Proc Natl Acad Sci USA"},{"key":"232_CR22","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1073\/pnas.94.2.684","volume":"94","author":"S Ramchandani","year":"1997","unstructured":"Ramchandani S, MacLeod AR, Pinard M, Von Hofe E, Szyf M: Inhibition of tumorigenesis by a cytosine-DNA methyltransferase, antisense oligodeoxynucleotide. Proc Natl Acad Sci USA. 1997, 94: 684-9. 10.1073\/pnas.94.2.684.","journal-title":"Proc Natl Acad Sci USA"},{"key":"232_CR23","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1093\/annonc\/mdf314","volume":"13","author":"J Goffin","year":"2002","unstructured":"Goffin J, Eisenhauer E: DNA methyltransferase inhibitors-state of the art. Ann Oncol. 2002, 13: 1699-716. 10.1093\/annonc\/mdf314.","journal-title":"Ann Oncol"},{"key":"232_CR24","first-page":"1442","volume":"4","author":"J Lyons","year":"2003","unstructured":"Lyons J, Bayar E, Fine G, McCullar M, Rolens R, Rubinfeld J, Rosenfeld C: Decitabine: development of a DNA methyltransferase inhibitor for hematological malignancies. Curr Opin Investig Drugs. 2003, 4: 1442-50.","journal-title":"Curr Opin Investig Drugs"},{"key":"232_CR25","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1093\/annonc\/mdg216","volume":"14","author":"DJ Stewart","year":"2003","unstructured":"Stewart DJ, Donehower RC, Eisenhauer EA, Wainman N, Shah AK, Bonfils C, MacLeod AR, Besterman JM, Reid GK: A phase I pharmacokinetic and pharmacodynamic study of the DNA methyltransferase 1 inhibitor MG98 administered twice weekly. Ann Oncol. 2003, 14: 766-74. 10.1093\/annonc\/mdg216.","journal-title":"Ann Oncol"},{"key":"232_CR26","first-page":"1596","volume":"9","author":"B Segura-Pacheco","year":"2003","unstructured":"Segura-Pacheco B, Trejo-Becerril C, Perez-Cardenas E, Taja-Chayeb L, Mariscal I, Chavez A, Acuna C, Salazar AM, Lizano M, Duenas-Gonzalez A: Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin Cancer Res. 2003, 9: 1596-603.","journal-title":"Clin Cancer Res"},{"key":"232_CR27","volume-title":"Lett Drug Design Discov","author":"E Angeles","year":"2005","unstructured":"Angeles E, Vazquez-Valadez VH, Vazquez-Valadez O, Velazquez-Sanchez AM, Ramirez A, Martinez L, Diaz-Barriga S, Romero-Rojas A, Cabrera G, Lopez-Casta\u00f1ares R, Duenas-Gonzalez A: Computational studies of 1-Hydrazinophtalazine (Hydralazine) as antineoplastic agent. Docking studies on methyltransferase. Lett Drug Design Discov. 2005"},{"key":"232_CR28","doi-asserted-by":"publisher","first-page":"9821","DOI":"10.1073\/pnas.93.18.9821","volume":"93","author":"JG Herman","year":"1996","unstructured":"Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA. 1996, 93: 9821-6. 10.1073\/pnas.93.18.9821.","journal-title":"Proc Natl Acad Sci USA"},{"key":"232_CR29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1101\/gr.224102. Article published online before print in March 2002","volume":"12","author":"LZ Strichman-Almashanu","year":"2002","unstructured":"Strichman-Almashanu LZ, Lee RS, Onyango PO, Perlman E, Flam F, Frieman MB, Feinberg AP: A genome-wide screen for normally methylated human CpG islands that can identify novel imprinted genes. Genome Res. 2002, 12: 543-54. 10.1101\/gr.224102. Article published online before print in March 2002.","journal-title":"Genome Res"},{"key":"232_CR30","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1002\/elps.200410040","volume":"26","author":"K Sandoval Guerrero","year":"2005","unstructured":"Sandoval Guerrero K, Revilla Vazquez A, Segura-Pacheco B, Duenas-Gonzalez A: Determination of 5-methyl-cytosine and cytosine in tumor DNA samples of cancer patients. Electrophoresis. 2005, 26: 1057-62. 10.1002\/elps.200410040.","journal-title":"Electrophoresis"},{"key":"232_CR31","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1006\/bbrc.1999.1187","volume":"262","author":"I Pogribny","year":"1999","unstructured":"Pogribny I, Yi P, James SJ: A sensitive new method for rapid detection of abnormal methylation patterns in global DNA and within CpG islands. Biochem Biophys Res Commun. 1999, 262: 624-8. 10.1006\/bbrc.1999.1187.","journal-title":"Biochem Biophys Res Commun"},{"key":"232_CR32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.2165\/00003088-199835010-00002","volume":"35","author":"R Kirsten","year":"1998","unstructured":"Kirsten R, Nelson K, Kirsten D, Heintz B: Clinical pharmacokinetics of vasodilators. Part II. Clin Pharmacokinet. 1998, 35: 9-36.","journal-title":"Clin Pharmacokinet"},{"key":"232_CR33","first-page":"7955","volume":"32","author":"LA Magee","year":"2003","unstructured":"Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P: Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003, 32: 7955-60.","journal-title":"BMJ"},{"key":"232_CR34","doi-asserted-by":"publisher","first-page":"18F","DOI":"10.1016\/S0002-9149(02)03336-2","volume":"9","author":"L Klein","year":"2003","unstructured":"Klein L, O'Connor CM, Gattis WA, Gattis WA, Zampino M, de Luca L, Vitarelli A, Fedele F, Gheorghiade M: Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: review of trials and practical considerations. Am J Cardiol. 2003, 9: 18F-40F. 10.1016\/S0002-9149(02)03336-2.","journal-title":"Am J Cardiol"},{"key":"232_CR35","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1002\/art.1780400811","volume":"40","author":"R Yung","year":"1997","unstructured":"Yung R, Chang S, Hemati N, Johnson K, Richardson B: Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo. Arthritis Rheum. 1997, 40: 1436-43.","journal-title":"Arthritis Rheum"},{"key":"232_CR36","first-page":"584","volume":"7","author":"AK Virmani","year":"2001","unstructured":"Virmani AK, Muller C, Rathi A, Zoechbauer-Mueller S, Mathis M, Gazdar AF: Aberrant methylation during cervical carcinogenesis. Clin Cancer Res. 2001, 7: 584-9.","journal-title":"Clin Cancer Res"},{"key":"232_CR37","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1476-4598-2-24","volume":"2","author":"G Narayan","year":"2003","unstructured":"Narayan G, Arias-Pulido H, Koul S, Vargas H, Zhang FF, Villella J, Schneider A, Terry MB, Mansukhani M, Murty VV: Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: Its relationship to clinical outcome. Mol Cancer. 2003, 2: 24-30. 10.1186\/1476-4598-2-24.","journal-title":"Mol Cancer"},{"key":"232_CR38","first-page":"1982","volume":"7","author":"SM Dong","year":"2001","unstructured":"Dong SM, Kim HS, Rha SH, Sidransky D: Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix. Clin Cancer Res. 2001, 7: 1982-6.","journal-title":"Clin Cancer Res"},{"key":"232_CR39","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1182\/blood.V100.8.2957","volume":"100","author":"M Daskalakis","year":"2002","unstructured":"Daskalakis M, Nguyen TT, Nguyen C, Guldberg P, Kohler G, Wijermans P, Jones PA, Lubbert M: Demethylation of a hypermethylated P15\/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment. Blood. 2002, 100: 2957-64. 10.1182\/blood.V100.8.2957.","journal-title":"Blood"},{"key":"232_CR40","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1182\/blood-2003-03-0687","volume":"103","author":"JP Issa","year":"2004","unstructured":"Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM: Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies. Blood. 2004, 103: 1635-40. 10.1182\/blood-2003-03-0687.","journal-title":"Blood"},{"key":"232_CR41","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00280-002-0563-y","volume":"51","author":"A Aparicio","year":"2003","unstructured":"Aparicio A, Eads CA, Leong LA, Laird PW, Newman EM, Synold TW, Baker SD, Zhao M, Weber JS: Phase I trial of continuous infusion 5-aza-2'-deoxycytidine. Cancer Chemother Pharmacol. 2003, 51: 231-9.","journal-title":"Cancer Chemother Pharmacol"},{"key":"232_CR42","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S1383-5742(96)00051-8","volume":"386","author":"JW Nyce","year":"1997","unstructured":"Nyce JW: Drug-induced DNA hypermethylation: a potential mediator of acquired drug resistance during cancer chemotherapy. Mutat Res. 1997, 386: 153-61.","journal-title":"Mutat Res"},{"key":"232_CR43","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1002\/art.1780240802","volume":"24","author":"TM Ludden","year":"1981","unstructured":"Ludden TM, McNay JL, Shepherd AM, Lin MS: Variability of plasma hydralazine concentrations in male hypertensive patients. Arthritis Rheum. 1981, 24: 987-93.","journal-title":"Arthritis Rheum"},{"key":"232_CR44","first-page":"959","volume":"70","author":"JE Dipierri","year":"1998","unstructured":"Dipierri JE, Alfaro E, Bejarano IF, Etchart AA: Acetylator phenotypes: allele frequency in northwestern Argentina and review of acetylator distribution in the Americas. Hum Biol. 1998, 70: 959-64.","journal-title":"Hum Biol"},{"key":"232_CR45","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nrc1279","volume":"4","author":"AP Feinberg","year":"2004","unstructured":"Feinberg AP, Tycko B: The history of cancer epigenetics. Nat Rev Cancer. 2004, 4: 143-53. 10.1038\/nrc1279.","journal-title":"Nat Rev Cancer"},{"key":"232_CR46","doi-asserted-by":"publisher","first-page":"E2","DOI":"10.1093\/nar\/gng002","volume":"31","author":"D Stach","year":"2003","unstructured":"Stach D, Schmitz OJ, Stilgenbauer S, Benner A, Dohner H, Wiessler M, Lyko F: Capillary electrophoretic analysis of genomic DNA methylation level. Nucleic Acids Res. 2003, 31: E2-10.1093\/nar\/gng002.","journal-title":"Nucleic Acids Res"},{"key":"232_CR47","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1210\/mend.11.13.0030","volume":"11","author":"JF Hu","year":"1997","unstructured":"Hu JF, Nguyen PH, Pham NV, Vu TH, Hoffman AR: Modulation of Igf2 genomic imprinting in mice induced by 5-azacytidine, an inhibitor of DNA methylation. Mol Endocrinol. 1997, 11: 1891-8. 10.1210\/me.11.13.1891.","journal-title":"Mol Endocrinol"},{"key":"232_CR48","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1200\/JCO.2004.04.185","volume":"22","author":"AT Chan","year":"2004","unstructured":"Chan AT, Tao Q, Robertson KD, Flinn IW, Mann RB, Klencke B, Kwan WH, Leung TW, Johnson PJ, Ambinder RF: Azacitidine induces demethylation of the Epstein-Barr virus genome in tumors. J Clin Oncol. 2004, 22: 1373-81. 10.1200\/JCO.2004.04.185.","journal-title":"J Clin Oncol"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-5-44.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2407-5-44\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-5-44","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2407-5-44.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T22:09:20Z","timestamp":1630447760000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/1471-2407-5-44"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,4,29]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["232"],"URL":"https:\/\/doi.org\/10.1186\/1471-2407-5-44","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,4,29]]},"assertion":[{"value":"25 January 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2005","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2005","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"44"}}