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Jean-Pierre Issa, M.D.

Present Title & Affiliation

Primary Appointment

Professor, American Cancer Society Clinical Research, Houston, TX
Co-Director, Center for Cancer Epigenetics, Institute of Basic Science Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX
Professor, Department of Leukemia, Chief, Section of Translational Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Education & Training

Degree-Granting Education

1987 The American University of Beirut, Beirut, Lebanon, MD, Doctor of Medicine
1983 The American Univeristy of Beirut, Beirut, Lebanon, BS, Biology

Postgraduate Training

1990-1994 Fellowship in Medical Oncology, The Johns Hopkins University, Baltimore, MD

Board Certifications

1/1993 Medical Oncology
1/1990 Internal Medicine

Experience/Service

Academic Appointments

Assistant Professor, Tumor Biology Division, The Johns Hopkins University School of Medicine, Baltimore, MD, 1/1995-1/1999

Administrative Appointments/Responsibilities

Program Leader, Hematologic Malignancies Program, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 2007-present
Chief, Section of Translational Research, Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 1/1999

Endowed Positions

Bessie McGoldrick Professorship,, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 2005-present

Honors and Awards

2007-2012 American Cancer Society Clinical Research Professorship
2007 MD Anderson Trust Fund
2007 Outstanding Faculty Award, The University of Texas M.D. Anderson Cancer Center
2005 Bessie McGoldrick Professorship in Clinical Cancer Care
2003 Elected to membership, The American Society For Clinical Investigation
2002 Scholar, Sidney Kimmel Foundation Symposium for Cancer Research
2000-2003 Scholar, George and Barbara Bush Foundation

Selected Publications

Peer-Reviewed Original Research Articles
1. Tellez CS, Shen L, Estécio MR, Jelinek J, Gershenwald JE, Issa JP. CpG island methylation profiling in human melanoma cell lines. Melanoma Res 19(3):146-55, 6/2009. PMID: 19441164.
2. Stewart DJ,Issa JP, Kurzrock R, Nunez MI, Jelinek J, Hong D, Oki Y, Guo Z, Gupta S, Wistuba II. Decitabine effect on tumor global DNA methylation and other parameters in a phase I trial in refractory solid tumors and lymphomas. Clin Cancer Res 15(11):3881-8, 6/2009. e-Pub 5/2009. PMID: 19470736.
3. Heinrichs S, Kulkarni RV, Bueso-Ramos CE, Levine RL, Loh ML, Li C, Neuberg D, Kornblau SM,Issa JP, Gilliland DG, Garcia-Manero G, Kantarjian HM, Estey EH, Look AT. Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics. Leukemia. e-Pub 4/2009. PMID: 19387468.
4. Figueiredo JC, Grau MV, Wallace K, Levine AJ, Shen L, Hamdan R, Chen X, Bresalier RS, McKeown-Eyssen G, Haile RW, Baron JA,Issa JP. Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics and Dietary and Genetic Factors. Cancer Epidemiol Biomarkers Prev 18(4):1041-9, 4/2009. e-Pub 3/2009. PMID: 19336559.
5. Ware CB, Wang L, Mecham BH, Shen L, Nelson AM, Bar M, Lamba DA, Dauphin DS, Buckingham B, Askari B, Lim R, Tewari M, Gartler SM, Issa JP, Pavlidis P, Duan Z, Blau CA. Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells. Cell Stem Cell 4(4):359-69, 4/2009. PMID: 19341625.
6. Aparicio A, North B, Barske L, Wang X, Bollati V, Weisenberger D, Yoo C, Tannir N, Horne E, Groshen S, Jones P, Yang A,Issa JP. LINE-1 methylation in plasma DNA as a biomarker of activity of DNA methylation inhibitors in patients with solid tumors. Epigenetics 4(3). e-Pub 4/2009. PMID: 19421002.
7. Watanabe Y, Kim HS, Castoro RJ, Chung W, Estecio MR, Kondo K, Guo Y, Ahmed SS, Toyota M, Itoh F, Suk KT, Cho MY, Shen L, Jelinek J,Issa JP. Sensitive and Specific Detection of Early Gastric Cancer with DNA Methylation Analysis of Gastric Washes. Gastroenterology 136(7). e-Pub 4/2009. PMID: 19375421.
8. Huang X, Ning J, Li Y, Estey E, Issa JP, Berry DA. Using short-term response information to facilitate adaptive randomization for survival clinical trials. Stat Med 28(12):1680-9, 3/2009. e-Pub 3/2009. PMID: 19326367.
9. De Padua Silva L, de Lima M, Kantarjian H, Faderl S, Kebriaei P, Giralt S, Davisson J, Garcia-Manero G, Champlin R, Issa JP, Ravandi F. Feasibility of allo-SCT after hypomethylating therapy with decitabine for myelodysplastic syndrome. Bone Marrow Transplant 43(11). e-Pub 1/2009. PMID: 19151791.
10. Kim MJ, White-Cross JA, Shen L, Issa JP, Rashid A. Hypomethylation of long interspersed nuclear element-1 in hepatocellular carcinomas. Mod Pathol 22(3). e-Pub 1/2009. PMID: 19136926.
11. Issa JP. Colon cancer: it's CIN or CIMP. Clin Cancer Res 14(19):5939-40, 10/1/2008. PMID: 18829469.
12. Qin T, Jelinek J, Si J, Shu J, Issa JP. Mechanisms of resistance to 5-aza-2'-deoxycytidine in human cancer cell lines. Blood. e-Pub 10/17/2008. PMID: 18931345.
13. Kantarjian H, O'Brien S, Cortes J, Wierda W, Faderl S, Garcia-Manero G, Issa JP, Estey E, Keating M, Freireich EJ. Therapeutic advances in leukemia and myelodysplastic syndrome over the past 40 years. Cancer 113(7 Suppl):1933-52, 10/1/2008. PMID: 18798533.
14. Kuang SQ, Tong WG, Yang H, Lin W, Lee MK, Fang ZH, Wei Y, Jelinek J, Issa JP, Garcia-Manero G. Genome-wide identification of aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia. Leukemia 8:1529-38, 8/2008. e-Pub 6/2008. PMID: 18528427.
15. Gao W, Kondo Y, Shen L, Shimizu Y, Sano T, Yamao K, Natsume A, Goto Y, Ito M, Murakami H, Osada H, Zhang J, Issa JP, Sekido Y. Variable DNA methylation patterns associatedwith progression of disease in hepatocellular carcinomas. Carcinogenesis 29(10). e-Pub 7/16/2008. PMID: 18632756.
16. Kantarjian H, O'Brien S, Ravandi F, Cortes J, Shan J, Bennett JM, List A, Fenaux P, Sanz G, Issa JP, Freireich EJ, Garcia-Manero GJ. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original international prgnostic scoring system. Cancer, July 10, 2008, 7/2008. PMID: 18618511.
17. Kroeger H, Jelinek J, Estecio MR, He R, Kondo K, Chung W, Zhang L, Shen L, Kantarjian HM, Bueso-Ramos CE, Issa JP. Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse. Blood, 6/2008.
18. Jabbour E,Issa JP, Garcia-Manero G, Kantarjian H. Evolution of decitabine development: accomplishments, ongoing investigations, and future strategies. Cancer 112(11):2341-51, 6/2008. PMID: 18398832.
19. Issa JP. Cancer prevention: epigenetics steps up to the plate. Cancer Prev Res (Phila Pa) 1(4). e-Pub 3/2008. PMID: 19138962.
20. Zuo X, Shen L,Issa JP, Moy O, Morris JS, Lippman SM, Shureiqi I. 15-Lipoxygenase-1 transcriptional silencing by DNA methyltransferase-1 independently of DNA methylation. FASEB J Jan 15 [Epub ahead of print], 2008.
21. Borthakur,G., Ahdab,S.E., Ravandi,F., Faderl,S., Ferrajoli,A., Newman,B., Issa JP and Kantarjian,H. Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine. Leuk.Lymphoma 49:690-695, 2008.
22. Boumber YA, Kondo Y, Chen X, Shen L, Guo Y, Tellez C, Estécio MR, Ahmed S, Issa JP. An Sp1/Sp3 binding polymorphism confers methylation protection. PLoS Genet 4(8):e1000162, 2008. PMCID: PMC2515197.
23. Wang,J., Bhutani,M., Pathak,A.K., Lang,W., Ren,H., Jelinek,J., He,R., Shen,L.,Issa JP, and Mao,L. Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner. Cancer Res 67:10647-10652, 2008.
24. Kondo Y, Shen L, Ahmed S, Boumber Y, Sekido Y, Haddad BR,Issa JP. Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells. PLoS ONE 3(4):e2037, 2008. PMCID: PMC2323574.
25. Jelinek,J., Li,J., Mnjoyan,Z., Issa JP, Prchal,J.T., and Afshar-Kharghan,V. Epigenetic control of PRV-1 expression on neutrophils. Exp.Hematol 35:1677-1683, 2008.
26. Suehiro,Y., Wong,C.W., Chirieac,L.R., Kondo,Y., Shen,L., Webb,C.R., Chan,Y.W., Chan,A.S., Chan,T.L., Wu,T.T., Rashid,A., Hamanaka,Y., Hinoda,Y., Shannon,R.L., Wang,X., Morris,J., Issa JP, Yuen,S.T., Leung,S.Y., and Hamilton,S.R. Epigenetic-Genetic Interactions in the APC/WNT, RAS/RAF, and P53 Pathways in Colorectal Carcinoma. Clin.Cancer Res. 14:2560-2569, 2008.
27. Kondo Y, Shen L, Cheng A, Ahmed S, Boumber Y, Charo C, Yamochi T, Urano T, Furukawa K, Kwabi-Addo B, Gold D, Sekido Y, Huang T, Issa JP. Gene silencing in cancer by histone H3 lysine 27 tri-methylation independent of promoter DNA methylation. Nature Genetics 40(6):741-50, 2008.
28. Chung,W., Kwabi-Addo,B., Ittmann,M., Jelinek,J., Shen,L., Yu,Y., Issa JP. Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling. PLoS.ONE 3:e2079, 2008.
29. Feng,W., Marquez,R.T., Lu,Z., Liu,J., Lu,K.H., Issa JP, Fishman,D.M., Yu,Y., and Bast,R.C., Jr. Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation. Cancer 112:1489-1502, 2008.
30. Lee,E.S., Issa JP, Roberts,D.B., Williams,M.D., Weber,R.S., Kies,M.S., and El Naggar,A.K. Quantitative Promoter Hypermethylation Analysis of Cancer-Related Genes in Salivary Gland Carcinomas: Comparison with Methylation-Specific PCR Technique and Clinical Significance. Clin.Cancer Res., 14:2664-2672, 2008.
31. Majewski,T., Lee,S., Jeong,J., Yoon,D.S., Kram,A., Kim,M.S., Tuziak,T., Bondaruk,J., Lee,S., Park,W.S., Tang,K.S., Chung,W., Shen,L., Ahmed,S.S., Johnston,D.A., Grossman,H.B., Dinney,C.P., Zhou,J.H., Harris,R.A., Snyder,C., Filipek,S., Narod,S.A., Watson,P., Lynch,H.T., Gazdar,A., Bar-Eli,M., Wu,X.F., McConkey,D.J., Baggerly,K., Issa JP, Benedict,W.F., Scherer,S.E., and Czerniak,B. Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy. Lab Invest, 2008. e-Pub 2008.
32. Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, Shu J, Chen X, Waterland RA,Issa JP. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet 3(10). e-Pub 9/2007. PMCID: PMC2041996.
33. Bazan E, Issa JP, Watanabe IS, Mandarim-de-Lacerda CA, Del Bel EA, Iyomasa MM. Ultrastructural and biochemical changes of the medial pterygoid muscle induced by unilateral exodontia. Micron, 8/2007.
34. Oki Y, Kantarjian HM, Gharibyan V, Jones D, O'Brien S, Verstovsek S, Cortes J, Morris GM, Garcia-Manero G, Issa JP. Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia. Cancer 109:899-906, 3/2007. PMID: 17236224.
35. Boumber YA, Kondo Y, Chen X, Shen L, Gharibyan V, Konishi K, Estey E, Kantarjian H, Garcia-Manero G, Issa JP. RIL, a LIM Gene on 5q31, Is Silenced by Methylation in Cancer and Sensitizes Cancer Cells to Apoptosis. Cancer Res 67(5):1997-2005, 3/2007. PMID: 17332327.
36. Kantarjian HM, O'Brien S, Huang X, Garcia-Manero G, Ravandi F, Cortes J, Shan J, Davisson J, Bueso-Ramos CE, Issa JP. Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience. Cancer 109(6):1133-7, 2/2007. PMID: 17315156.
37. Liu TX, Becker MW, Jelinek J, Wu WS, Deng M, Mikhalkevich N, Hsu K, Bloomfield CD, Stone RM, DeAngelo DJ, Galinsky IA, Issa JP, Clarke MF, Look AT. Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Nat Med 13(1):78-83, 1/2007. PMID: 17159988.
38. Kim J, Kim JY, Song KS, Lee YH, Seo JS, Jelinek J, Goldschmidt-Clermont PJ, Issa JP. Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence. Biochim Biophys Acta 1772:72-80, 1/2007. PMID: 17110088.
39. Shen L, Guo Y, Chen X, Ahmed S, Issa JP. Optimizing annealing temperature overcomes bias in bisulfite PCR methylation analysis. Biotechniques 42(1):48, 50, 52 passim, 1/2007. PMID: 17269485.
40. Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O'Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan J, Davis J, Giles F, Saba HI, Issa JP. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109:52-7, 1/2007. PMID: 16882708.
41. Kantarjian HM, O'Brien S, Shan J, Aribi A, Garcia-Manero G, Jabbour E, Ravandi F, Cortes J, Davisson J, Issa JP. Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome. Cancer 109(2):265-73, 1/2007. PMID: 17133405.
42. Huang,X., Biswas,S., Oki,Y., Issa JP., and Berry,D.A. A parallel phase I/II clinical trial design for combination therapies. Biometrics 63:429-436, 2007.
43. Kwabi-Addo,B., Chung,W., Shen,L., Ittmann,M., Wheeler,T., Jelinek,J., and Issa JP. Age-related DNA methylation changes in normal human prostate tissues. Clin.Cancer Res 13:3796-3802, 2007.
44. Kondo,Y., Shen,L., Suzuki,S., Kurokawa,T., Masuko,K., Tanaka,Y., Kato,H., Mizuno,Y., Yokoe,M., Sugauchi,F., Hirashima,N., Orito,E., Osada,H., Ueda,R., Guo,Y., Chen,X., Issa JP, and Sekido,Y. Alterations of DNA methylation and histone modifications contribute to gene silencing in hepatocellular carcinomas. Hepatol.Res 37:974-983, 2007.
45. Shen L, Catalano PJ, Benson AB 3rd, O'Dwyer P, Hamilton SR, Issa JP. Association between DNA Methylation and Shortened Survival in Patients with Advanced Colorectal Cancer Treated with 5-Fluorouracil Based Chemotherapy. Clin Cancer Res 13(20):6093-8, 2007.
46. Shen L, Kondo Y, Ahmed S, Boumber Y, Konishi K, Guo Y, Chen X, Vilaythong JN, Issa JP. Cancer Res. Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel 67(23):11335-43, 2007.
47. Feng W, Shen L, Wen S, Rosen DG, Jelinek J, Hu X, Huang S, Huang M, Liu J, Sahin AA, Hunt KK, Bast RC Jr, Shen Y, Issa JP, Yu Y. Correlation between CpG methylation profiles and hormone receptor status in breast cancers. Breast Cancer Res 9(4):R57, 2007.
48. Wang J, Bhutani M, Pathak AK, Lang W, Ren H, Jelinek J, He R, Shen L, Issa JP, Mao L. Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner. Cancer Res 67(22):10647-52, 2007.
49. Shen L, Kondo Y, Ahmed S, Boumber Y, Konishi K, Guo Y, Chen X, Vilaythong JN, Issa JP. Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel. Cancer Res 67(23):11335-43, 2007.
50. Qin T, Youssef EM, Jelinek J, Chen R, Yang AS, Garcia-Manero G, Issa JP. Effect of cytarabine and decitabine in combination in human leukemic cell lines. Clin Cancer Res 13(14):4225-32, 2007.
51. Yanada M, Huang X, Garcia-Manero G, O'brien S, Ravandi F, Borthakur G, Faderl S, Issa JP, Kantarjian H, Estey E. Effect of haematological improvement on survival in patients given targeted therapy as initial treatment of acute myeloid leukaemia or high-risk myelodysplastic syndrome. Br J Haematol 138(4):555-7, 2007.
52. Temam,S., Kawaguchi,H., El Naggar,A.K., Jelinek,J., Tang,H., Liu,D.D., Lang,W., Issa JP, Lee,J.J., and Mao,L. Epidermal growth factor receptor copy number alterations correlate with poor clinical outcome in patients with head and neck squamous cancer. J.Clin.Oncol 25:2164-2170, 2007.
53. Jelinek J, Li J, Mnjoyan Z, Issa JP, Prchal JT, Afshar-Kharghan V. Epigenetic control of PRV-1 expression on neutrophils. Exp Hematol 35(11):1677.e1-1677.e8, 2007.
54. Lee S, Jeong J, Majewski T, Scherer SE, Kim MS, Tuziak T, Tang KS, Baggerly K, Grossman HB, Zhou JH, Shen L, Bondaruk J, Ahmed SS, Samanta S, Spiess P, Wu X, Filipek S, McConkey D, Bar-Eli M, Issa JP, Benedict WF, Czerniak B. Forerunner genes contiguous to RB1 contribute to the development of in situ neoplasia. Proc Natl Acad Sci U S A 104(34):13732-7, 2007.
55. Jelinek J, Issa JP, He R, Cmejla R, Cmejlova J, Pospisilova D. Genes are not Silenced by DNA Methylation in Diamond Blackfan Anemia. J Pediatr Hematol Oncol 29(3):207-208, 2007.
56. Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, Shu J, Chen X, Waterland RA, Issa JP. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG islands promoters. PLoS Genet 3(10):e181, 2007.
57. Estecio MR, Yan PS, Ibrahim AE, Tellez CS, Shen L, Huang TH, Issa JP. High-throughput methylation profiling by MCA coupled to CpG island microarray. Genome Res Sep 4 [Epub ahead of print], 2007.
58. Choi SH, Byun HM, Kwan JM, Issa JP, Yang AS. Hydroxycarbamide in combination with azacitidine or decitabine is antagonistic on DNA methylation inhibition. Br J Haematol 138(5):616-23, 2007.
59. Choi IS, Estecio MR, Nagano Y, Kim DH, White JA, Yao JC, Issa JP, Rashid A. Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Mod Pathol 20(7):802-10, 2007.
60. Oki Y, Jelinek J, Shen L, Kantarjian HM, Issa JP. Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia. Blood Nov 30 [Epub ahead of print], 2007.
61. Shen L, Toyota M, Kondo Y, Lin E, Zhang L, Guo Y, Hernandez NS, Chen X, Ahmed S, Konishi K, Hamilton SR, Issa JP. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci U S A 104(47):18654-9, 2007.
62. Estecio MR, Gharibyan V, Shen L, Ibrahim AE, Doshi K, He R, Jelinek J, Yang AS, Yan PS, Huang TH, Tajara EH, Issa JP. LINE-1 Hypomethylation in Cancer Is Highly Variable and Inversely Correlated with Microsatellite Instability. PLoS ONE 2:e399, 2007.
63. Oki,Y., Jelinek,J., Beran,M., Verstovsek,S., Kantarjian,H.M., Issa JP. Mutations and promoter methylation status of NPM1 in myeloproliferative disorders. Haematologica 91:1147-1148, 2007.
64. Tabe Y, Konopleva M, Kondo Y, Contractor R, Tsao T, Konoplev S, Shi Y, Ling X, Watt JC, Tsutsumi-Ishii Y, Ohsaka A, Nagaoka I, Issa JP, Kogan SC, Andreeff M. PPARgamma-Active Triterpenoid CDDO Enhances ATRA-Induced Differentiation in APL. Cancer Biol Ther 6(12):Sept 4 [epub ahead of print], 2007.
65. Konishi K, Shen L, Wang S, Meltzer SJ, Harpaz N, Issa JP. Rare CpG Island Methylator Phenotype in Ulcerative Colitis-Associated Neoplasias. Gastroenterology 132(4):1254-60, 2007.
66. Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O'Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan J, Davi J, Giles F, Saba H, Issa JP. Results of a Randomized Study of Three Schedules of Low-Dose Decitabine in Higher Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia. Blood 109:52-57, 2007.
67. Jelinek,J., Issa JP, He,R., Cmejla,R., Cmejlova,J., and Pospisilova,D. RPS19 and JAK2 genes are not silenced by DNA methylation in diamond blackfan anemia. J.Pediatr.Hematol.Oncol 29:207-208, 2007.
68. Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F, Cortes J, Wierda WG, Ouzounian S, Quezada A, Pierce S, Estey EH, Issa JP, Kantarjian HM, Garcia-Manero G. Safety and clinical activity of the combination of 5-azacytidine, valproic acid and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 110:2302-2308, 2007.
69. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S, Rytting M, Wierda WG, Ravandi F, Koller C, Xiao L, Faderl S, Estrov Z, Cortes J, O'Brien S, Estey E, Bueso-Ramos C, Fiorentino J, Jabbour E, Issa JP. Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood 108:3271-9, 11/2006. PMID: 16882711.
70. Tabe Y, Konopleva M, Kondo Y, Contractor R, Jin L, Ruvolo V, Tsutsumi-Ishii Y, Miyake K, Miyake N, Ohsaka A, Nagaoka I, Issa JP, Andreeff M. PML-RARalpha and AML1-ETO translocations are rarely associated with methylation of the RARbeta2 promoter. Ann Hematol 85:689-704, 10/2006. PMID: 16832676.
71. Estecio MR, Youssef EM, Rahal P, Fukuyama EE, Gois-Filho JF, Maniglia JV, Goloni-Bertollo EM, Issa JP, Tajara EH. LHX6 is a sensitive methylation marker in head and neck carcinomas. Oncogene 25:5018-26, 8/2006. PMID: 16732332.
72. Gollob JA, Sciambi CJ, Peterson BL, Richmond T, Thoreson M, Moran K, Dressman HK, Jelinek J, Issa JP. Phase I trial of sequential low-dose 5-aza-2'-deoxycytidine plus high-dose intravenous bolus interleukin-2 in patients with melanoma or renal cell carcinoma. Clin Cancer Res 12(15):4619-27, 8/2006. PMID: 16899610.
73. Yang AS, Doshi KD, Choi SW, Mason JB, Mannari RK, Gharybian V, Luna R, Rashid A, Shen L, Estecio MR, Kantarjian HM, Garcia-Manero G, Issa JP. DNA methylation changes after 5-aza-2'-deoxycytidine therapy in patients with leukemia. Cancer Res 66:5495-503, 5/2006. PMID: 16707479.
74. Oki Y,Issa JP. Review: recent clinical trials in epigenetic therapy. Rev Recent Clin Trials 1(2):169-82, 5/2006. PMID: 18473969.
75. Yu,Y., Luo,R., Lu,Z., Wei,F.W., Badgwell,D., Issa JP, Rosen,D.G., Liu,J., and Bast,R.C., Jr. Biochemistry and biology of ARHI (DIRAS3), an imprinted tumor suppressor gene whose expression is lost in ovarian and breast cancers. 407:455-468, 2006.
76. Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, Dipersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106(8):1794-803, 2006.
77. da Silva MA, Issa JP, Vitti M, da Silva AM, Semprini M, Regalo SC. Electromyographical analysis of the masseter muscle in dentulous and partially toothless patients with temporomandibular joint disorders. Electromyogr Clin Neurophysiol 46(5):263-8, 2006.
78. Montero AJ, Diaz-Montero CM, Mao L, Youssef EM, Estecio M, Shen L, Issa JP. Epigenetic Inactivation of EGFR by CpG Island Hypermethylation in Cancer. Cancer Biol Ther 5(11):1494-1501, 2006.
79. Shu J, Jelinek J, Chang H, Shen L, Qin T, Chung W, Oki Y, Issa JP. Silencing of bi-directional promoters by DNA methylation in tumorigenesis. Cancer Research 66(10):5077-84, 2006.
80. Jelinek J, Oki Y, Gharibyan V, Bueso-Ramos C, Prchal JT, Verstovsek S, Beran M, Estey E, Kantarjian HM, Issa JP. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 106(10):3370-3, 11/2005. PMID: 16037387.
81. Toyota M, Issa JP. Epigenetic changes in solid and hematopoietic tumors. Semin Oncol 32(5):521-30, 10/2005. PMID: 16210093.
82. Canalli AA, Yang H, Jeha S, Hoshino K, Sanchez-Gonzalez B, Brandt M, Pierce S, Kantarjian H,Issa JP, Garcia-Manero G. Aberrant DNA methylation of a cell cycle regulatory pathway composed of P73, P15 and P57KIP2 is a rare event in children with acute lymphocytic leukemia. Leuk Res 29(8):881-5, 8/2005. PMID: 15978938.
83. Issa JP, Kantarjian HM. Introduction: emerging role of epigenetic therapy: focus on decitabine. Semin Hematol 42(3 Suppl 2):S1-2, 7/2005. PMID: 16015499.
84. Issa JP, Gharibyan V, Cortes J, Jelinek J, Morris G, Verstovsek S, Talpaz M, Garcia-Manero G, Kantarjian HM. Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate. J Clin Oncol 10:3948-56, 6/2005. PMID: 15883410.
85. Murai M, Toyota M, Satoh A, Suzuki H, Akino K, Mita H, Sasaki Y, Ishida T, Shen L, Garcia-Manero G, Issa JP, Hinoda Y, Tokino T, Imai K. Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours. Br J Cancer 92(6):1165-72, 3/2005. PMID: 15756280.
86. Beach,R., Chan,A.O., Wu,T.T., White,J.A., Morris,J.S., Lunagomez,S., Broaddus,R.R., Issa JPHamilton,S.R., and Rashid,A. BRAF mutations in aberrant crypt foci and hyperplastic polyposis. Am.J.Pathol 166:1069-1075, 2005.
87. Chan AO, Soliman AS, Zhang Q, Rashid A, Bedier A, Houlihan PS, Mokhtar N, Al-Masri N, Ozbeck U, Yaghan R, Kandilci A, Omar S, Kapran Y, Dizdaroglu F, Bondy ML, Amos CI, Issa JP, Levin B, Hamilton SR. Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries. Clin Cancer Research 11(23):8281-7, 2005.
88. Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse PS, Prasad AR, Einsphar JG, Buckmeier J, Alberts DS, Hamilton SR, Issa JP. MGMT promoter methylation and field defect in sporadic colorectal cancer. J Natl Cancer Inst 97(18):1330-8, 2005.
89. Issa JP. Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection. Nat.Clin.Pract.Oncol 2 Suppl 1:S24-S29, 2005.
90. Chirieac,L.R., Shen,L., Catalano,P.J., Issa JP, and Hamilton,S.R. Phenotype of microsatellite-stable colorectal carcinomas with CpG island methylation. Am.J.Surg.Pathol 29:429-436, 2005.
91. Akino,K., Toyota,M., Suzuki,H., Mita,H., Sasaki,Y., Ohe-Toyota,M., Issa JP, Hinoda,Y., Imai,K., and Tokino,T. The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer. Gastroenterology 129:156-169, 2005.
92. Youssef EM, Issa JP, Lotan R. Regulation of RARbeta1 expression in head and neck cancer cells by cell density-dependent chromatin remodeling. Cancer Biol Ther 3(10):1002-6, 10/2004. PMID: 15467435.
93. Maruya S, Issa JP, Weber RS, Rosenthal DI, Haviland JC, Lotan R, El-Naggar AK. Differential methylation status of tumor-associated genes in head and neck squamous carcinoma: incidence and potential implications. Clin Cancer Res 10(11):3825-30, 6/2004. PMID: 15173091.
94. Kondo Y, Shen L, Yan PS, Huang TH, Issa JP. Chromatin immunoprecipitation microarrays for identification of genes silenced by histone H3 lysine 9 methylation. Proc Natl Acad Sci U S A 101(19):7398-403, 5/2004. PMID: 15123805.
95. Youssef EM, Chen XQ, Higuchi E, Kondo Y, Garcia-Manero G, Lotan R, Issa JP. Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers. Cancer Res 64(7):2411-7, 4/2004. PMID: 15059893.
96. Youssef EM, Lotan D, Issa JP, Wakasa K, Fan YH, Mao L, Hassan K, Feng L, Lee JJ, Lippman SM, Hong WK, Lotan R. Hypermethylation of the retinoic acid receptor-beta(2) gene in head and neck carcinogenesis. Clin Cancer Res 10(5):1733-42, 3/2004. PMID: 15014026.
97. 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 103(5):1635-40, 3/2004. PMID: 14604977.
98. Yang AS, Estecio MR, Doshi K, Kondo Y, Tajara EH, Issa JP. A simple method for assessing global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res 32:e38, 2004. PMID: 14973332.
99. Youssef EM, Estecio MR, Issa JP. Methylation and regulation of expression of different retinoic acid receptor beta isoforms in human colon cancer. Cancer Biol Ther 3(1):82-6, 2004. PMID: 14726683.
100. List AF, Vardiman J, Issa JP, DeWitte TM. Myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program:297-317, 2004. PMID: 15561689.
101. Obata T, Toyota M, Satoh A, Sasaki Y, Ogi K, Akino K, Suzuki H, Murai M, Kikuchi T, Mita H, Itoh F, Issa JP, Tokino T, Imai K. Identification of HRK as a target of epigenetic inactivation in colorectal and gastric cancer. Clin Cancer Res 9(17):6410-8, 12/2003. PMID: 14695142.
102. Yang AS, Estecio MR, Garcia-Manero G, Kantarjian HM, Issa JP. Comment on "Chromosomal instability and tumors promoted by DNA hypomethylation" and "Induction of tumors in nice by genomic hypomethylation". Science 302(5648):1153; author reply 1153, 11/2003. PMID: 14615517.
103. Kim SG, Wu TT, Lee JH, Yun YK, Issa JP, Hamilton SR, Rashid A. Comparison of epigenetic and genetic alterations in mucinous cystic neoplasm and serous microcystic adenoma of pancreas. Mod Pathol 16(11):1086-94, 11/2003. PMID: 14614047.
104. Issa JP. Decitabine. Curr Opin Oncol 15(6):446-51, 11/2003. PMID: 14624227.
105. Belinsky SA, Klinge DM, Stidley CA, Issa JP, Herman JG, March TH, Baylin SB. Inhibition of DNA methylation and histone deacetylation prevents murine lung cancer. Cancer Res 63(21):7089-93, 11/2003. PMID: 14612500.
106. Issa JP. Age-related epigenetic changes and the immune system. Clin Immunol 109(1):103-8, 10/2003. PMID: 14585281.
107. Cavalli LR, Urban CA, Dai D, de Assis S, Tavares DC, Rone JD, Bleggi-Torres LF, Lima RS, Cavalli IJ, Issa JP, Haddad BR. Genetic and epigenetic alterations in sentinel lymph nodes metastatic lesions compared to their corresponding primary breast tumors. Cancer Genet Cytogenet 146(1):33-40, 10/2003. PMID: 14499694.
108. Frazier ML, Xi L, Zong J, Viscofsky N, Rashid A, Wu EF, Lynch PM, Amos CI, Issa JP. Association of the CpG island methylator phenotype with family history of cancer in patients with colorectal cancer. Cancer Res 63(16):4805-8, 8/2003. PMID: 12941799.
109. Fujii S, Luo RZ, Yuan J, Kadota M, Oshimura M, Dent SR, Kondo Y, Issa JP, Bast RC, Jr, Yu Y. Reactivation of the silenced and imprinted alleles of ARHI is associated with increased histone H3 acetylation and decreased histone H3 lysine 9 methylation. Hum Mol Genet 12(15):1791-800, 8/2003. PMID: 12874100.
110. Kantarjian HM, O'Brien S, Cortes J, Giles FJ, Faderl S, Issa JP, Garcia-Manero G, Rios MB, Shan J, Andreeff M, Keating M, Talpaz M. Results of decitabine (5-aza-2'deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. Cancer 98(3):522-8, 8/2003. PMID: 12879469.
111. Yuan J, Luo RZ, Fujii S, Wang L, Hu W, Andreeff M, Pan Y, Kadota M, Oshimura M, Sahin AA, Issa JP, Bast RC, Jr, Yu Y. Aberrant methylation and silencing of ARHI, an imprinted tumor suppressor gene in which the function is lost in breast cancers. Cancer Res 63(14):4174-80, 7/2003. PMID: 12874023.
112. Kondo Y, Issa JP. Enrichment for histone H3 lysine 9 methylation at Alu repeats in human cells. J Biol Chem 278(30):27658-62, 7/2003. PMID: 12724318.
113. Colella S, Shen L, Baggerly KA, Issa JP, Krahe R. Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. Biotechniques 35(1):146-50, 7/2003. PMID: 12866414.
114. Li H, Myeroff L, Smiraglia D, Romero MF, Pretlow TP, Kasturi L, Lutterbaugh J, Rerko RM, Casey G, Issa JP, Willis J, Willson JK, Plass C, Markowitz SD. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci U S A 100(14):8412-7, 7/2003. PMID: 12829793.
115. Toyota M, Sasaki Y, Satoh A, Ogi K, Kikuchi T, Suzuki H, Mita H, Tanaka N, Itoh F, Issa JP, Jair KW, Schuebel KE, Imai K, Tokino T. Epigenetic inactivation of CHFR in human tumors. Proc Natl Acad Sci U S A 100(13):7818-23, 6/2003. PMID: 12810945.
116. Shen L, Toyota M, Kondo Y, Obata T, Daniel S, Pierce S, Imai K, Kantarjian HM, Issa JP, Garcia-Manero G. Aberrant DNA methylation of p57KIP2 identifies a cell-cycle regulatory pathway with prognostic impact in adult acute lymphocytic leukemia. Blood 101(10):4131-6, 5/2003. PMID: 12586619.
117. Kim SG, Chan AO, Wu TT, Issa JP, Hamilton SR, Rashid A. Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas. Gastroenterology 124(5):1300-10, 5/2003. PMID: 12730870.
118. Yang AS, Issa JP. Mitoxantrone: a hypomethylating agent? Cancer Biol Ther 2(3):264-5, May-Jun, 5/2003. PMID: 12878862.
119. Shen L, Kondo Y, Hamilton SR, Rashid A, Issa JP. P14 methylation in human colon cancer is associated with microsatellite instability and wild-type p53. Gastroenterology 124(3):626-33, 3/2003. PMID: 12612901.
120. Garcia-Manero G, Jeha S, Daniel J, Williamson J, Albitar M, Kantarjian HM, Issa JP. Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia. Cancer 97(3):695-702, 2/2003. PMID: 12548613.
121. On-On Chan A, Kim SG, Bedeir A, Issa JP, Hamilton SR, Rashid A. CpG island methylation in carcinoid and pancreatic endocrine tumors. Oncogene 22:924-34, 2/2003. PMID: 12584572.
122. Kondo Y, Shen L, Issa JP. Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer. Mol Cell Biol 23(1):206-15, 2003. PMID: 12482974.
123. Shen L, Kondo Y, Issa JP, Garcia-Manero G. Lack of p21(CIP1) DNA methylation in acute lymphocytic leukemia. Blood 100(9):3432-3; author reply 3433-4, 11/2002. PMID: 12412576.
124. Garcia-Manero G, Daniel J, Smith TL, Kornblau SM, Lee MS, Kantarjian HM, Issa JP. DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia. Clin Cancer Res 8(7):2217-24, 7/2002. PMID: 12114423.
125. Kantarjian HM, Talpaz M, O'Brien S, Smith TL, Giles FJ, Faderl S, Thomas DA, Garcia-Manero G, Issa JP, Andreeff M, Kornblau SM, Koller C, Beran M, Keating M, Rios MB, Shan J, Resta D, Capdeville R, Hayes K, Albitar M, Freireich EJ, Cortes JE. Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results. Clin Cancer Res 8(7):2177-87, 7/2002. PMID: 12114418.
126. Kantarjian HM, O'Brien S, Cortes JE, Smith TL, Rios MB, Shan J, Yang Y, Giles FJ, Thomas DA, Faderl S, Garcia-Manero G, Jeha S, Wierda W, Issa JP, Kornblau SM, Keating M, Resta D, Capdeville R, Talpaz M. Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Clin Cancer Res 8(7):2167-76, 7/2002. PMID: 12114417.
127. Garcia-Manero G, Bueso-Ramos C, Daniel J, Williamson J, Kantarjian HM, Issa JP. DNA methylation patterns at relapse in adult acute lymphocytic leukemia. Clin Cancer Res 8(6):1897-903, 6/2002. PMID: 12060634.
128. On-On Chan A, Broaddus RR, Houlihan PS, Issa JP, Hamilton SR, Rashid A. CpG island methylation in aberrant crypt foci of the colorectum. Am J Pathol 160:1823-30, 5/2002. PMID: 12000733.
129. Shen L, Ahuja N, Shen Y, Habib NA, Toyota M, Rashid A, Issa JP. DNA methylation and environmental exposures in human hepatocellular carcinoma. J Natl Cancer Inst 94(10):755-61, 5/2002. PMID: 12011226.
130. Soria JC, Lee HY, Lee JI, Wang L, Issa JP, Kemp BL, Liu DD, Kurie JM, Mao L, Khuri FR. Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation. Clin Cancer Res 8(5):1178-84, 5/2002. PMID: 12006535.
131. Moinova HR, Chen WD, Shen L, Smiraglia D, Olechnowicz J, Ravi L, Kasturi L, Myeroff L, Plass C, Parsons R, Minna J, Willson JK, Green SB, Issa JP, Markowitz SD. HLTF gene silencing in human colon cancer. Proc Natl Acad Sci U S A 99(7):4562-7, 4/2002. PMID: 11904375.
132. Kikuchi T, Toyota M, Itoh F, Suzuki H, Obata T, Yamamoto H, Kakiuchi H, Kusano M, Issa JP, Tokino T, Imai K. Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumors. Oncogene 21(17):2741-9, 4/2002. PMID: 11965547.
133. On-On Chan A, Issa JP, Morris JS, Hamilton SR, Rashid A. Concordant CpG Island Methylation in Hyperplastic Polyposis. American Journal of Pathology 160:529-536, 2002.
134. Ueki T, Toyota M, Skinner H, Walter KM, Yeo CJ, Issa JP, Hruban RH, Goggins M. Identification and characterization of differentially methylated CpG islands in pancreatic carcinoma. Cancer Res 61(23):8540-6, 12/2001. PMID: 11731440.
135. Anderson GR, Brenner BM, Swede H, Chen N, Henry WM, Conroy JM, Karpenko MJ, Issa JP, Bartos JD, Brunelle JK, Jahreis GP, Kahlenberg MS, Basik M, Sait S, Rodriguez-Bigas MA, Nowak NJ, Petrelli NJ, Shows TB, Stoler DL. Intrachromosomal genomic instability in human sporadic colorectal cancer measured by genome-wide allelotyping and inter-(simple sequence repeat) PCR. Cancer Res 61(22):8274-83, 11/2001. PMID: 11719460.
136. Rashid A, Shen L, Morris JS, Issa JP, Hamilton SR. CpG island methylation in colorectal adenomas. Am J Pathol 159(3):1129-35, 9/2001. PMID: 11549606.
137. Peng H, Shen N, Qian L, Sun XL, Koduru P, Goodwin LO, Issa JP, Broome JD. Hypermethylation of CpG islands in the mouse asparagine synthetase gene: relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells. Br J Cancer 85(6):930-5, 9/2001. PMID: 11556848.
138. Luo RZ, Peng H, Xu F, Bao J, Pang Y, Pershad R, Issa JP, Liao WS, Bast RC, Jr, Yu Y. Genomic structure and promoter characterization of an imprinted tumor suppressor gene ARHI. Biochim Biophys Acta 1519(3):216-22, 6/2001. PMID: 11418188.
139. Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA. Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res 61(9):3573-7, 5/2001. PMID: 11325821.
140. Toyota M, Kopecky KJ, Toyota MO, Jair KW, Willman CL, Issa JP. Methylation profiling in acute myeloid leukemia. Blood 97(9):2823-9, 5/2001. PMID: 11313277.
141. Santini V, Kantarjian HM, Issa JP. Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications. Ann Intern Med 134(7):573-86, 4/2001. PMID: 11281740.
142. Toyota M, Shen L, Ohe-Toyota M, Hamilton SR, Sinicrope FA, Issa JP. Aberrant methylation of the Cyclooxygenase 2 CpG island in colorectal tumors. Cancer Res 60(15):4044-8, 8/2000. PMID: 10945606.
143. Esteller M, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Watkins DN, Issa JP, Sidransky D, Baylin SB, Herman JG. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis. Cancer Res 60(9):2368-71, 5/2000. PMID: 10811111.
144. Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, Goggins M. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res 60(7):1835-9, 4/2000. PMID: 10766168.
145. Ying AK, Hassanain HH, Roos CM, Smiraglia DJ, Issa JP, Michler RE, Caligiuri M, Plass C, Goldschmidt-Clermont PJ. Methylation of the estrogen receptor-alpha gene promoter is selectively increased in proliferating human aortic smooth muscle cells. Cardiovasc Res 46(1):172-9, 4/2000. PMID: 10727665.
146. Toyota M, Ohe-Toyota M, Ahuja N,Issa JP. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proc Natl Acad Sci U S A 97(2):710-5, 1/2000. PMID: 10639144.
147. Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, Baylin SB, Issa JP. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 59(21):5438-42, 11/1999. PMID: 10554013.
148. Toyota M, Ho C, Ohe-Toyota M, Baylin SB, Issa JP. Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5' CpG island in human tumors. Cancer Res 59(18):4535-41, 9/1999. PMID: 10493502.
149. Post WS, Goldschmidt-Clermont PJ, Wilhide CC, Heldman AW, Sussman MS, Ouyang P, Milliken EE, Issa JP. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovasc Res 43(4):985-91, 9/1999. PMID: 10615426.
150. Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP. CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 96(15):8681-6, 7/1999. PMID: 10411935.
151. Li Q, Kopecky KJ, Mohan A, Willman CL, Appelbaum FR, Weick JK, Issa JP. Estrogen receptor methylation is associated with improved survival in adult acute myeloid leukemia. Clin Cancer Res 5(5):1077-84, 5/1999. PMID: 10353741.
152. Toyota M, Ho C, Ahuja N, Jair KW, Li Q, Ohe-Toyota M, Baylin SB, Issa JP. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res 59(10):2307-12, 5/1999. PMID: 10344734.
153. Li Q, Ahuja N, Burger PC, Issa JP. Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Oncogene 18(21):3284-9, 5/1999. PMID: 10359534.
154. Issa JP, Kantarjian H, Mohan A, O'Brien S, Cortes J, Pierce S, Talpaz M. Methylation of the ABL1 promoter in chronic myelogenous leukemia: lack of prognostic significance. Blood 93(6):2075-80, 3/1999. PMID: 10068681.
155. Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 58(23):5489-94, 12/1998. PMID: 9850084.
156. Mikovits JA, Young HA, Vertino P, Issa JP, Pitha PM, Turcoski-Corrales S, Taub DD, Petrow CL, Baylin SB, Ruscetti FW. Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production. Mol Cell Biol 18(9):5166-77, 9/1998. PMID: 9710601.
157. Li Q, Jedlicka A, Ahuja N, Gibbons MC, Baylin SB, Burger PC, Issa JP. Concordant methylation of the ER and N33 genes in glioblastoma multiforme. Oncogene 16(24):3197-202, 6/1998. PMID: 9671399.
158. Herman JG, Umar KiA, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, nzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA, Baylin SB. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 95(12):6870-5, 6/1998. PMID: 9618505.
159. Ahuja N, Mohan AL, Li Q, Stolker JM, Herman JG, Hamilton SR, Baylin SB, Issa JP. Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Res 57(16):3370-4, 8/1997. PMID: 9269998.
160. Issa JP, Zehnbauer BA, Kaufmann SH, Biel MA, Baylin SB. HIC1 hypermethylation is a late event in hematopoietic neoplasms. Cancer Res 57(9):1678-81, 5/1997. PMID: 9135007.
161. Herman JG, Civin CI, Issa JP, Collector MI, Sharkis SJ, Baylin SB. Distinct patterns of inactivation of p15INK4B and p16INK4A characterize the major types of hematological malignancies. Cancer Res 57(5):837-41, 3/1997. PMID: 9041182.
162. Issa JP, Vertino PM, Boehm CD, Newsham IF, Baylin SB. Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. Proc Natl Acad Sci U S A 93(21):11757-62, 10/1996. PMID: 8876210.
163. Issa JP, Baylin SB, Belinsky SA. Methylation of the estrogen receptor CpG island in lung tumors is related to the specific type of carcinogen exposure. Cancer Res 56(16):3655-8, 8/1996. PMID: 8706002.
164. Lapidus RG, Ferguson AT, Ottaviano YL, Parl FF, Smith HS, Weitzman SA, Baylin SB, Issa JP, Davidson NE. Methylation of estrogen and progesterone receptor gene 5' CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res 2(5):805-10, 5/1996. PMID: 9816234.
165. Belinsky SA, Nikula KJ, Baylin SB, Issa JP. Increased cytosine DNA-methyltransferase activity is target-cell-specific and an early event in lung cancer. Proc Natl Acad Sci U S A 93(9):4045-50, 4/1996. PMID: 8633014.
166. Issa JP, Zehnbauer BA, Civin CI, Collector MI, Sharkis SJ, Davidson NE, Kaufmann SH, Baylin SB. The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. Cancer Res 56(5):973-77, 3/1996. PMID: 8640788.
167. Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin SB. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 55(20):4525-30, 10/1995. PMID: 7553621.
168. Wales MM, Biel MA, el Deiry W, Nelkin BD, Issa JP, Cavenee WK, Kuerbitz SJ, Baylin SB. p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3. Nat Med 1(6):570-7, 6/1995. PMID: 7585125.
169. Vertino PM, Issa JP, Pereira-Smith OM, Baylin SB. Stabilization of DNA methyltransferase levels and CpG island hypermethylation precede SV40-induced immortalization of human fibroblasts. Cell Growth Differ 5(12):1395-402, 12/1994. PMID: 7696189.
170. Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB. Methylation of the Estrogen Receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7(4):536-40, 8/1994. PMID: 7951326.
171. Ottaviano YL, Issa JP, Parl FF, Smith HS, Baylin SB, Davidson NE. Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. Cancer Res 54(10):2552-5, 5/1994. PMID: 8168078.
172. Wu J, Issa JP, Herman J, Bassett DE, Jr, Nelkin BD, Baylin SB. Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells. Proc Natl Acad Sci U S A 90(19):8891-5, 10/1993. PMID: 8415627.
173. Issa JP, Vertino PM, Wu J, Sazawal S, Celano P, Nelkin BD, Hamilton SR, Baylin SB. Increased cytosine DNA-methyltransferase activity during colon cancer progression. J Natl Cancer Inst 85(15):1235-40, 8/1993. PMID: 8331684.

Invited Articles
1. Batty N, Malouf GG, Issa JP. Histone deacetylase inhibitors as anti-neoplastic agents. Cancer Lett. e-Pub 4/2009. PMID: 19345475.
2. Oki Y, Aoki E, Issa JP. Decitabine--bedside to bench. Crit Rev Oncol Hematol 61:140-52, 2/2007. PMID: 17023173.
3. Plimack ER, Kantarjian HM, Issa JP. Decitabine and its role in the treatment of hematopoietic malignancies. Leuk Lymphoma 48(8):1472-81, 2007.
4. Issa JP. DNA methylation as a therapeutic target in cancer. Clin Cancer Res 13(6):1634-7, 2007.
5. Konishi K, Issa JP. Targeting aberrant chromatin structure in colorectal carcinomas. Cancer J 13(1):49-55, 2007.
6. Konishi K, Issa JP. Targeting aberrant chromatin structure in colorectal carcinomas. Cancer J 13(1):49-55, 2007.
7. Oki Y, Issa JP. Treatment options in advanced myelodysplastic syndrome, with emphasis on epigenetic therapy. Int J Hematol 86(4):306-14, 2007.
8. Oki Y, Issa JP. Treatment options in advanced myelodysplastic syndrome, with emphasis on epigenetic therapy. Int J Hematol 86(4):306-14, 2007.
9. Kantarjian HM, Issa JP. Decitabine dosing schedules. Semin Hematol 42(3 Suppl 2):S17-22, 7/2005. PMID: 16015500.
10. Issa JP, Byrd JC. Decitabine in chronic leukemias. Semin Hematol 42(3 Suppl 2):S43-9, 7/2005. PMID: 16015505.
11. Issa JP, Kantarjian HM, Kirkpatrick P. Azacitidine. Nat Rev Drug Discov 4:275-6, 2005.
12. Issa JP. DNA methylation in the treatment of hematologic malignancies. Clin Adv Hematol Oncol. 3(9):684-6, 2005.
13. Issa JP, Kantarjian HM. Emerging role of epigenetic therapy: focus on decitabine. Semin Hematol Jul;42(2 Suppl 2)(S1-2), 2005.
14. Garcia-Manero G, Issa JP. Histone deacetylase inhibitors: a review of their clinical status as antineoplastic agents. Cancer Invest 23(7):635-42, 2005. PMID: 16305991.
15. Issa JP. Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection. Nat Clin Pract Oncol. 2 Suppl:1:S24-9, 2005.
16. Issa JP. CpG island methylator phenotype in cancer. Nat Rev Cancer 4(12):988-93, 12/2004. PMID: 15573120.
17. Rashid A, Issa JP. CpG island methylation in gastroenterologic neoplasia: a maturing field. Gastroenterology 127(5):1578-88, 11/2004. PMID: 15521024.
18. Kondo Y, Issa JP. Epigenetic changes in colorectal cancer. Cancer Metastasis Rev 23(1-2):29-39, 2004. PMID: 15000147.
19. Issa JP. Epigenetic variation and human disease. J Nutr 132(8 Suppl):2388S-2392S, 8/2002. PMID: 12163698.
20. Issa JPJ. Epigenetics in Colorectal Cancer. Current Opinion in Gastroenterology 18:68-73, 2002.
21. Santini V, Kantarjian H , Issa JPJ. DNA methylation in hematologic malignancies-pathophysiology and therapeutic implications. Annals of Int. Med 134:573-586, 2001.
22. Ahuja N, Issa JP. Aging, methylation and cancer. Histol Histopathol 15(3):835-42, 7/2000. PMID: 10963127.
23. Garcia-Manero G and Issa JPJ. CpG island methylation in cancer. Cancer Research Alert 1(12):133-136, 2000.
24. Toyota M, Issa JP. The role of DNA hypermethylation in human neoplasia. Electrophoresis 21(2):329-33, 2000. PMID: 10675010.
25. Toyota M, Issa JP. CpG island methylator phenotypes in aging and cancer. Semin Cancer Biol 9(5):349-57, 10/1999. PMID: 10547343.
26. Issa JP. Aging, DNA methylation and cancer. Crit Rev Oncol Hematol 32(1):31-43, 9/1999. PMID: 10586353.
27. Lengauer C, Issa JP. The role of epigenetics in cancer. DNA Methylation, Imprinting and the Epigenetics of Cancer--an American Association for Cancer Research Special Conference. Las Croabas, Puerto Rico, 12-16 1997 December. Mol Med Today 4(3):102-3, 3/1998. PMID: 9575489.
28. Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res 72:141-96, 1998. PMID: 9338076.
29. Issa JP, Baylin SB, Herman JG. DNA methylation changes in hematologic malignancies: biologic and clinical implications. Leukemia 11 Suppl 1:S7-11, 3/1997. PMID: 9130685.
30. Belinsky SA, Nikula KJ, Baylin SB, Issa JP. A microassay for measuring cytosine DNA methyltransferase activity during tumor progression. Toxicol Lett 82-83:335-40, 12/1995. PMID: 8597074.

Editorials
1. Plimack ER, Stewark DJ,Issa JP. Combining epigenetic and cytotoxic therapy in the treatment of solid tumors. J Clin Oncol 25(29):4519-21, 2007.
2. Issa JP, Shen L, Toyota M. CIMP, at last. Gastroenterology 129(3):1121-4, 2005.
3. Issa JP. Methylation and Prognosis-of Molecular Clocks and Hypermethylator Phenotypes. Clin. Cancer Res 9:2879-81, 2003.
4. Issa JP, Baylin SB. Epigenetics and Human Disease. (News and Views). Nature Medicine 2:281-282, 1996.
Other Articles
1. Shu J, Jelinek J, Chang H, Shen L, Qin T, Chung W, Oki Y, Issa JP. Silencing of bidirectional promoters by DNA methylation in tumorigenesis. Cancer Res 66(10):5077-84, 5/2006. PMID: 16707430.

Book Chapters
1. Yu Y, Luo R, Lu Z, Feng W, Badgwell D, Issa JPJ, Rosen D, Liu J, Bast R. Biochemistry and Biology of ARHI (DIRAS3), and Imprinted Tumor Suppressor Gene Whose Expression is Lost in Ovarian and Breast Cancers. In: Methods In Enzymology. 407, 455-468, 2006.
2. Garcia-Manero G, Issa JPJ. The role of DNA hypomethylating agents in cancer treatment. In: Progress In Oncology 2004. 6, 131-158, 2004.
3. Yu Y, Fuji S, Yuan J, Luo RZ, Wang L, Bao J, Kadota M, Oshimura M, Dent SR, Issa J-PJ, Bast RC. Epigenetic regulation of ARHI in Breast and Ovarian Cancer Cells. In: Proceedings of the NY Academy of Sciences. 983, 268-277, 2003.
4. Toyota M , Issa J-PJ. Methylated CpG Island Amplification for Methylation Analysis and Cloning Differentially Methylated Sequences. In: In Methods in Molecular Biology: DNA Methylation Protocols. 200, 101-110, 2002.
5. Issa J-PJ. The Aging Epigenome. The Epigenome: Molecular Hide and Seek. In: Prolonging Life. Wiley Publishing, 2002.
6. Issa J-PJ. CpG Island methylation in aging and cancer. In: Curr Top Microbiol Immunol. 249, 101-18, 2000.
7. Issa J-PJ. The epigenetics of colorectal cancer. In: Proceedings of the N. Y. Academy of Sciences. 910, 140-53, 2000.
8. Issa JPJ. Hypermethylator phenotypes in aging and cancer. In: DNA Alterations in Cancer: Genetic and Epigenetic Changes. Ed(s) M. Ehrlich. 1999: BioTechniques Books, Eaton Publishing, 311-322, 1999.

Letters to the Editor
1. Oki Y, Jelinek J, Beran M, Verstovsek S, Kantarjian HM, Issa JP. Mutations and promoter methylation status of NPM1 in myeloproliferative disorders. Haematologica 91(8):1147-8, 8/2006. PMID: 16870548.

Grant & Contract Support

Title: Stand Up to Cancer Dream Team: "Bringing epigenetic therapy to the forefront of cancer management"
Funding Source: American Association for Cancer Research (AACR)
Role: Project Leader
Principal Investigator: Baylin S
Duration: 7/1/2009 - 6/30/2012

Last updated: 9/11/2009