Jean Pierre Issa

Summary

Affiliation: The University of Texas
Country: USA

Publications

  1. ncbi Accelerated age-related CpG island methylation in ulcerative colitis
    J P Issa
    University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 61:3573-7. 2001
  2. pmc Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling
    Woonbok Chung
    Department of Leukemia, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 3:e2079. 2008
  3. pmc An Sp1/Sp3 binding polymorphism confers methylation protection
    Yanis A Boumber
    Department of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, Texas, United States of America
    PLoS Genet 4:e1000162. 2008
  4. pmc Mechanisms of resistance to decitabine in the myelodysplastic syndrome
    Taichun Qin
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 6:e23372. 2011
  5. ncbi Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection
    Jean Pierre Issa
    Section of Translational Research, Department of Leukemia at the MD Anderson Cancer Center, University of Texas, Houston 77030, USA
    Nat Clin Pract Oncol 2:S24-9. 2005
  6. ncbi Decitabine in chronic leukemias
    Jean Pierre J Issa
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Semin Hematol 42:S43-9. 2005
  7. ncbi Age-related epigenetic changes and the immune system
    Jean Pierre Issa
    Department of Leukemia, University of Texas at M D Anderson Cancer Center, Houston, TX 77401, USA
    Clin Immunol 109:103-8. 2003
  8. ncbi Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies
    Jean Pierre J Issa
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 103:1635-40. 2004
  9. ncbi Azacitidine
    Jean Pierre Issa
    Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston 77030, USA
    Nat Rev Drug Discov . 2005
  10. doi Colon cancer: it's CIN or CIMP
    Jean Pierre Issa
    University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Clin Cancer Res 14:5939-40. 2008

Research Grants

  1. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2001
  2. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2006
  3. University of Texas M.D. Anderson Cancer SPORE-Leukemia
    Jean Pierre Issa; Fiscal Year: 2007
  4. Randomized study of combined epigenetic therapy
    Jean Pierre Issa; Fiscal Year: 2007
  5. Randomized study of combined epigenetic therapy
    Jean Pierre Issa; Fiscal Year: 2009
  6. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2007
  7. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2007
  8. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2006
  9. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2002
  10. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2003

Detail Information

Publications126 found, 100 shown here

  1. ncbi Accelerated age-related CpG island methylation in ulcerative colitis
    J P Issa
    University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 61:3573-7. 2001
    ....
  2. pmc Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling
    Woonbok Chung
    Department of Leukemia, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 3:e2079. 2008
    ..Our data identify new targets of transcriptional silencing in cancer, and provide new biomarkers that could be useful in screening for prostate cancer and other cancers...
  3. pmc An Sp1/Sp3 binding polymorphism confers methylation protection
    Yanis A Boumber
    Department of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, Texas, United States of America
    PLoS Genet 4:e1000162. 2008
    ..Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state...
  4. pmc Mechanisms of resistance to decitabine in the myelodysplastic syndrome
    Taichun Qin
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 6:e23372. 2011
    ..Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS...
  5. ncbi Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection
    Jean Pierre Issa
    Section of Translational Research, Department of Leukemia at the MD Anderson Cancer Center, University of Texas, Houston 77030, USA
    Nat Clin Pract Oncol 2:S24-9. 2005
    ..In the future, combination strategies to increase gene reactivation and to take advantage of increased expression of target genes may be critical for achieving optimal results...
  6. ncbi Decitabine in chronic leukemias
    Jean Pierre J Issa
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Semin Hematol 42:S43-9. 2005
    ....
  7. ncbi Age-related epigenetic changes and the immune system
    Jean Pierre Issa
    Department of Leukemia, University of Texas at M D Anderson Cancer Center, Houston, TX 77401, USA
    Clin Immunol 109:103-8. 2003
    ..The contribution of epigenetic changes to the altered immune function observed in aging humans deserves careful investigation...
  8. ncbi Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies
    Jean Pierre J Issa
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 103:1635-40. 2004
    ..There was no correlation between P15 methylation at baseline or after therapy and response to decitabine. We conclude that decitabine is effective in myeloid malignancies, and low doses are as or more effective than higher doses...
  9. ncbi Azacitidine
    Jean Pierre Issa
    Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston 77030, USA
    Nat Rev Drug Discov . 2005
    ..It is also a pioneering example of an agent that targets 'epigenetic' gene silencing, a mechanism that is exploited by cancer cells to inhibit the expression of genes that counteract the malignant phenotype...
  10. doi Colon cancer: it's CIN or CIMP
    Jean Pierre Issa
    University of Texas M D Anderson Cancer Center, Houston, TX, USA
    Clin Cancer Res 14:5939-40. 2008
    ..There are at least three different subsets with distinct clinico-pathologic features, with important implications for preventions, screening, and therapy...
  11. ncbi Decitabine
    Jean Pierre Issa
    Department of Leukemia, M D Anderson Cancer Center, Houston, TX 77030, USA
    Curr Opin Oncol 15:446-51. 2003
    ..These advances have turned this agent from just another cytosine analogue into a targeted drug aimed at reversing epigenetic silencing in cancer cells. Here, recent clinical and translational studies with decitabine are reviewed...
  12. ncbi Phase II study of low-dose decitabine in patients with chronic myelogenous leukemia resistant to imatinib mesylate
    Jean Pierre J Issa
    Department of Leukemia and Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 23:3948-56. 2005
    ..To determine the activity of decitabine, a DNA methylation inhibitor, in imatinib-refractory or intolerant chronic myelogenous leukemia...
  13. ncbi Azacitidine
    Jean Pierre J Issa
    Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Rev Drug Discov 4:275-6. 2005
  14. ncbi CpG island methylator phenotype in cancer
    Jean Pierre Issa
    Jean Pierre Issa is at the Department of Leukemia, M D Anderson Cancer Center, Unit 425, 1515 Holcombe, Houston, Texas 77030, USA
    Nat Rev Cancer 4:988-93. 2004
    ..Furthermore, CIMP-associated cancers seem to have a distinct epidemiology, a distinct histology, distinct precursor lesions and distinct molecular features...
  15. ncbi Epigenetic variation and human disease
    Jean Pierre Issa
    Department of Leukemia, The University of Texas at M D Anderson Cancer Center, Houston 77030, USA
    J Nutr 132:2388S-2392S. 2002
    ..It is suggested that epigenetic variation related to aging, lifestyle, exposures and possibly genetic factors, is one of the modulators of acquired, age-related human diseases, including neoplasia...
  16. pmc Epigenetic changes in the myelodysplastic syndrome
    Jean Pierre Issa
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA
    Hematol Oncol Clin North Am 24:317-30. 2010
    ....
  17. doi Time to think outside the (genetic) box
    Jean Pierre J Issa
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA
    Cancer Prev Res (Phila) 4:6-8. 2011
    ..Here, we discuss the implications of this work in terms of the etiology, risk, and potential prevention of cancer...
  18. ncbi DNA methylation as a therapeutic target in cancer
    Jean Pierre J Issa
    University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Clin Cancer Res 13:1634-7. 2007
    ..These drugs have now been approved for clinical use in the United States in the treatment of myelodysplastic syndrome, thus opening the floodgate for a whole new approach to cancer therapy--epigenetic therapy...
  19. ncbi Epigenetic regulation of ARHI in breast and ovarian cancer cells
    Yinhua Yu
    Department of Experimental Therapeutics, The University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Ann N Y Acad Sci 983:268-77. 2003
    ..Reactivation of both the silenced paternal and imprinted maternal alleles can be achieved by demethylation and inhibition of histone deacetylation...
  20. pmc Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities
    Farhad Ravandi
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 115:5746-51. 2009
    ..Outcome of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) with chromosome 5 and 7 abnormalities (excluding del 5[q]) has been poor, with <10% of patients alive at 2 years...
  21. ncbi Hypermethylation of the retinoic acid receptor-beta(2) gene in head and neck carcinogenesis
    Emile M Youssef
    Departments of Thoracic Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77345, USA
    Clin Cancer Res 10:1733-42. 2004
    ..This study was conducted to determine whether RAR-beta(2) gene expression in such lesions can be silenced by promoter methylation...
  22. ncbi Results of decitabine (5-aza-2'deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia
    Hagop M Kantarjian
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 98:522-8. 2003
    ..Decitabine is a hypomethylating agent that has shown encouraging preliminary anti-CML activity. This study evaluated the activity and toxicity of decitabine in different phases of CML...
  23. pmc Report of a phase 1/2 study of a combination of azacitidine and cytarabine in acute myelogenous leukemia and high-risk myelodysplastic syndromes
    Gautam Borthakur
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Leuk Lymphoma 51:73-8. 2010
    ..Complete remission was achieved in 2 of 6 minimally pre-treated patients. We conclude that the combination of azacitidine and cytarabine is feasible but has limited activity in relapsed/refractory AML...
  24. pmc Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience
    Hagop M Kantarjian
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 109:1133-7. 2007
    ..The comparative efficacy of these 2 forms of treatment in MDS is unknown. The objective of the current study was to compare the efficacy and toxicity profiles of decitabine and intensive chemotherapy in MDS...
  25. pmc Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer
    Yutaka Kondo
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Mol Cell Biol 23:206-15. 2003
    ..Our results suggest that reduced H3 Lys-4 methylation and increased H3 Lys-9 methylation play a critical role in the maintenance of promoter DNA methylation-associated gene silencing in colorectal cancer...
  26. ncbi Rare CpG island methylator phenotype in ulcerative colitis-associated neoplasias
    Kazuo Konishi
    Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Gastroenterology 132:1254-60. 2007
    ..Whether this translates into hypermethylation in UC-associated cancers (UC-Cs) is not known...
  27. ncbi Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation
    Jean Charles Soria
    Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Clin Cancer Res 8:1178-84. 2002
    ....
  28. ncbi Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries
    Annie O Chan
    Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Clin Cancer Res 11:8281-7. 2005
    ..International differences in molecular pathology have not been studied extensively but have implications for the management of patients in different countries and of immigrant patients...
  29. pmc The heterogeneous prognosis of patients with myelodysplastic syndrome and chromosome 5 abnormalities: how does it relate to the original lenalidomide experience in MDS?
    Hagop Kantarjian
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Cancer 115:5202-9. 2009
    ..To define the prognosis in myelodysplastic syndrome (MDS) and deletion 5q with or without other cytogenetic abnormalities...
  30. ncbi 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
    Andreia A Canalli
    Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Leuk Res 29:881-5. 2005
    ..003). These results indicate that differences in DNA methylation of specific molecular pathways may contribute to the prognostic differences known to occur between pediatric and adult patients with ALL...
  31. ncbi Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome
    Hagop M Kantarjian
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 109:265-73. 2007
    ..In this study, the authors update their experience with decitabine in patients with MDS and analyze the cytogenetic response patterns and prognostic factors associated with decitabine therapy...
  32. pmc Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia
    Guillermo Garcia-Manero
    Department of Leukemia, Box 428, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Blood 108:3271-9. 2006
    ..In summary, this combination of epigenetic therapy in leukemia was safe and active, and was associated with transient reversal of aberrant epigenetic marks...
  33. ncbi Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy
    Elias Jabbour
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 116:3830-4. 2010
    ..The prognosis of patients with myelodysplastic syndrome (MDS) after decitabine failure is not known...
  34. ncbi Histone deacetylase inhibitors: a review of their clinical status as antineoplastic agents
    Guillermo Garcia-Manero
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Invest 23:635-42. 2005
    ..In this article, we provide a brief introduction to the field of histone deacetylation inhibition in cancer and review the most relevant clinical data so far published...
  35. ncbi Current and future management options for myelodysplastic syndromes
    Jeffrey Bryan
    Department of Leukemia, The University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Drugs 70:1381-94. 2010
    ..This review focuses on supportive care modalities, the approved agents indicated for the treatment of MDS and future directions for the treatment of MDS, including agents under clinical investigation...
  36. ncbi Comparison of epigenetic and genetic alterations in mucinous cystic neoplasm and serous microcystic adenoma of pancreas
    Sang Geol Kim
    Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4095, USA
    Mod Pathol 16:1086-94. 2003
    ..The differences in genetic alterations but not epigenetic alterations may explain the pathogenesis and progression to malignancy of these cystic tumors of pancreas...
  37. pmc Feasibility of therapy with hypomethylating agents in patients with renal insufficiency
    G Nicolas Batty
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Clin Lymphoma Myeloma Leuk 10:205-10. 2010
    ..To our knowledge, the feasibility of therapy with hypomethylating agents (HAs) in patients with renal insufficiency (RI) has not been examined...
  38. ncbi Decitabine in the treatment of myelodysplastic syndromes
    Fabio P S Santos
    Department of Leukemia, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0428, Houston, TX 77030, USA
    Expert Rev Anticancer Ther 10:9-22. 2010
    ..There are still some issues concerning the ideal dose and schedule of decitabine for treating patients with MDS. This article focuses on the most recent clinical studies of decitabine for therapy of MDS...
  39. doi Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation
    Yutaka Kondo
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
    Nat Genet 40:741-50. 2008
    ..These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation...
  40. ncbi Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner
    Jie Wang
    Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 67:10647-52. 2007
    ..We conclude that promoter DNA methylation can be differentially regulated and DeltaDNMT3Bs are involved in regulation of such promoter-specific de novo DNA methylation...
  41. ncbi A parallel phase I/II clinical trial design for combination therapies
    Xuelin Huang
    Department of Biostatistics and Applied Mathematics, University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Biometrics 63:429-36. 2007
    ..The simulations show that the proposed design saves sample size, has better power, and efficiently assigns more patients to doses with higher efficacy levels...
  42. ncbi Phenotype of microsatellite-stable colorectal carcinomas with CpG island methylation
    Lucian R Chirieac
    Department of Pathology, Division of Pathology and Laboratory Medicine, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Am J Surg Pathol 29:429-36. 2005
    ..5, P = 0.03). Our epigenotype-phenotype correlation study shows that microsatellite-stable CRC with CpG island methylation have a distinctive pathologic phenotype with both similarities to and differences from MSI-H tumors...
  43. ncbi Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System
    Hagop Kantarjian
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 113:1351-61. 2008
    ....
  44. ncbi Targeting aberrant chromatin structure in colorectal carcinomas
    Kazuo Konishi
    Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
    Cancer J 13:49-55. 2007
    ..Drugs that inhibit DNA methylation and histone deacetylation are in use in the clinic and should be tested in colorectal malignancy...
  45. ncbi MGMT promoter methylation and field defect in sporadic colorectal cancer
    Lanlan Shen
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Natl Cancer Inst 97:1330-8. 2005
    ..The DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal cancer. We hypothesized that MGMT methylation could be one of the mediators of field cancerization in the colon mucosa...
  46. ncbi PPARgamma-active triterpenoid CDDO enhances ATRA-induced differentiation in APL
    Yoko Tabe
    Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Cancer Biol Ther 6:1967-77. 2007
    ..In summary, these results provide rationale for the combined targeting of RAR and PPARgamma nuclear receptors in the therapy of APL...
  47. doi Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation
    Weiwei Feng
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Cancer 112:1489-502. 2008
    ..Two imprinted genes, paternally expressed 3 (PEG3) and aplasia Ras homologue member I (ARHI), are the most frequently down-regulated in ovarian cancers on gene expression arrays...
  48. doi Therapeutic advances in leukemia and myelodysplastic syndrome over the past 40 years
    Hagop Kantarjian
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Cancer 113:1933-52. 2008
    ..In patients with MDS, it was recently demonstrated that epigenetic therapy with hypomethylating agents improved survival. Much therapeutic progress has been witnessed in leukemia and MDS, and much more is expected to occur soon...
  49. doi Decitabine effect on tumor global DNA methylation and other parameters in a phase I trial in refractory solid tumors and lymphomas
    David J Stewart
    M D Anderson Cancer Center, Houston, Texas, USA
    Clin Cancer Res 15:3881-8. 2009
    ..By hypomethylating genes, decitabine may up-regulate factors required for chemotherapeutic cytotoxicity. Platinum-resistant cells may have reduced expression of the copper/platinum transporter CTR1...
  50. ncbi PML-RARalpha and AML1-ETO translocations are rarely associated with methylation of the RARbeta2 promoter
    Yoko Tabe
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 448, Houston, TX 77030, USA
    Ann Hematol 85:689-704. 2006
    ..These results demonstrate that oncogenic PML-RARalpha and AML1-ETO translocations are rarely associated with RARbeta2 promoter methylation in primary AML samples...
  51. pmc Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer
    Lanlan Shen
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030
    Proc Natl Acad Sci U S A 104:18654-9. 2007
    ..Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease...
  52. pmc Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma
    Yutaka Suehiro
    Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Clin Cancer Res 14:2560-9. 2008
    ....
  53. ncbi Epigenetic changes in colorectal cancer
    Yutaka Kondo
    Department of Leukemia, University of Texas at M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Metastasis Rev 23:29-39. 2004
    ..Understanding epigenetic alterations as a driving force in neoplasia opens new fields of research in epidemiology, risk assessment, and treatment in CRCs...
  54. ncbi RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis
    Yanis A Boumber
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA
    Cancer Res 67:1997-2005. 2007
    ..In MDS, RIL methylation is a marker of adverse prognosis independent of chromosome 5 and 7 deletions. Our data suggest that RIL is a good candidate TSG silenced by hypermethylation in cancer...
  55. pmc LINE-1 methylation in plasma DNA as a biomarker of activity of DNA methylation inhibitors in patients with solid tumors
    Ana Aparicio
    Department of Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
    Epigenetics 4:176-84. 2009
    ..Ongoing studies will determine whether changes in LINE-1 methylation in plasma DNA occur as a result of treatment with DNA methylation inhibitors and parallel changes in tumor tissue DNA...
  56. ncbi Decitabine and its role in the treatment of hematopoietic malignancies
    Elizabeth R Plimack
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Leuk Lymphoma 48:1472-81. 2007
    ..Investigations of combinations of decitabine with other agents, including histone deacetylase inhibitors, are currently ongoing in the hope of substantially prolonging survival in patients with hematologic malignancies...
  57. ncbi Evolution of decitabine development: accomplishments, ongoing investigations, and future strategies
    Elias Jabbour
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer 112:2341-51. 2008
    ..Combination therapies that augment the epigenetic effect of decitabine will likely improve responses and extend its use for the treatment of other malignancies...
  58. ncbi Biochemistry and biology of ARHI (DIRAS3), an imprinted tumor suppressor gene whose expression is lost in ovarian and breast cancers
    Yinhua Yu
    The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Methods Enzymol 407:455-68. 2006
    ..Growth of ovarian and breast cancer xenografts is reversibly suppressed by ARHI, but expression of the NTD mutant produced only a limited inhibitory effect on growth of xenografts...
  59. pmc Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine
    Gautam Borthakur
    Department of Leukemia, M D Anderson Cancer Center, Houston, TX 77030, USA
    Leuk Lymphoma 49:690-5. 2008
    ..We conclude that clinically significant responses with decitabine can be seen in patients post-azacitidine failure without significant toxicity...
  60. ncbi Aberrant methylation and silencing of ARHI, an imprinted tumor suppressor gene in which the function is lost in breast cancers
    Jiuhong Yuan
    Department of Experimental Therapeutics, The University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 63:4174-80. 2003
    ..Other epigenetic modifications such as hypermethylation in CpG island III may also contribute to the loss of ARHI expression...
  61. ncbi Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas
    Sang Geol Kim
    Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, 77030, USA
    Gastroenterology 124:1300-10. 2003
    ..Carcinomas of the extrahepatic bile ducts, ampulla of Vater, and duodenum are uncommon, and their epigenetic and genetic alterations are not well characterized...
  62. pmc Chromatin immunoprecipitation microarrays for identification of genes silenced by histone H3 lysine 9 methylation
    Yutaka Kondo
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 101:7398-403. 2004
    ..This unbiased approach confirms the tight coupling between DNA methylation and histone modifications in cancer and could be used to probe gene silencing in nonneoplastic conditions as well...
  63. ncbi Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome
    Andres O Soriano
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 110:2302-8. 2007
    ..VPA blood levels were higher in responders (P < .005). In conclusion, the combination studied is safe and has significant clinical activity. This clinical trial was registered at www.clinicaltrials.gov as no. NCT00326170...
  64. ncbi Differential methylation status of tumor-associated genes in head and neck squamous carcinoma: incidence and potential implications
    Shin ichiro Maruya
    Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 10:3825-30. 2004
    ..Concurrent methylation analysis of multiple, functionally distinct genes may provide important information on their differential alterations and potential association in head and neck squamous carcinogenesis...
  65. pmc Correlation between CpG methylation profiles and hormone receptor status in breast cancers
    Weiwei Feng
    Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Breast Cancer Res 9:R57. 2007
    ..The present study was undertaken to determine whether methylation of a set of growth-suppressor genes would correlate to the expression of estrogen receptors (ERs) and progesterone receptors (PRs)...
  66. ncbi Age-related DNA methylation changes in normal human prostate tissues
    Bernard Kwabi-Addo
    Department of Pathology, Baylor College of Medicine, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Clin Cancer Res 13:3796-802. 2007
    ..We examined the extent of gene methylation in pathologically normal human prostate as a function of age...
  67. pmc Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil based chemotherapy
    Lanlan Shen
    The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 13:6093-8. 2007
    ..We sought to determine the prognostic significance of CIMP in advanced colorectal cancer patients treated with 5-fluorouracil (5-FU) in an Eastern Cooperative Oncology Group clinical trial...
  68. ncbi Reactivation of the silenced and imprinted alleles of ARHI is associated with increased histone H3 acetylation and decreased histone H3 lysine 9 methylation
    Satoshi Fujii
    Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Hum Mol Genet 12:1791-800. 2003
    ....
  69. ncbi Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia
    Yasuhiro Oki
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 109:899-906. 2007
    ..A Phase II study was performed on low-dose decitabine, a DNA methyltransferase inhibitor, in combination with imatinib in patients with CML in accelerated phase (AP) and myeloid blastic phase (BP)...
  70. pmc Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia
    Yasuhiro Oki
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 111:2382-4. 2008
    ..Our data suggest a predominantly noncytotoxic mechanism of action for decitabine, leading to altered biology of the neoplastic clone and/or normal cells. This trial was registered at www.ClinicalTrials.gov as #NCT00067808...
  71. ncbi Silencing of bidirectional promoters by DNA methylation in tumorigenesis
    Jingmin Shu
    Department of Leukemia, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 66:5077-84. 2006
    ....
  72. ncbi Decitabine--bedside to bench
    Yasuhiro Oki
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Crit Rev Oncol Hematol 61:140-52. 2007
    ..Herein, we summarize the results of recent clinical trials of decitabine in hematologic malignancies, and review the translational research into decitabine's mechanism of clinical activity...
  73. pmc A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements
    Allen S Yang
    Department of Leukemia, M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Nucleic Acids Res 32:e38. 2004
    ..This method can be used as a surrogate marker of genome-wide methylation changes. In addition, it is less labor intensive and requires less DNA than previous methods of assessing global DNA methylation...
  74. ncbi Review: recent clinical trials in epigenetic therapy
    Yasuhiro Oki
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX, 77030, USA
    Rev Recent Clin Trials 1:169-82. 2006
    ..No agent in this class has been studied in a phase III trial, but several agents have been or are being studied in phase II trials. Further research is needed to determine the appropriate patient selection and dosing schedules...
  75. ncbi Analysis of epigenetic modifications by next generation sequencing
    Shoudan Liang
    Department of Bioinformatics and Computational Biology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Conf Proc IEEE Eng Med Biol Soc 2009:6730. 2009
    ..Several techniques useful in epigenetic data analysis will be discussed, mapping tags to reference genome incorporating all known SNPs, analysis of chIP-seq data, as well as restriction enzyme-based DNA methylation analysis...
  76. ncbi DNA methylation in the treatment of hematologic malignancies
    Jean Pierre Issa
    The University of Texas, M D Anderson Cancer Center, Houston, TX 77030, USA
    Clin Adv Hematol Oncol 3:684-6. 2005
  77. ncbi Quantitative promoter hypermethylation analysis of cancer-related genes in salivary gland carcinomas: comparison with methylation-specific PCR technique and clinical significance
    Eung Seok Lee
    Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Clin Cancer Res 14:2664-72. 2008
    ....
  78. ncbi Epidermal growth factor receptor copy number alterations correlate with poor clinical outcome in patients with head and neck squamous cancer
    Stephane Temam
    Molecular Biology Laboratory and Department of Thoracic Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 25:2164-70. 2007
    ..Recent studies showed that EGFR inhibitors are effective for patients with HNSCC. This study analyzed the genetic nature of EGFR gene in HNSCC and its clinical correlations...
  79. pmc Using short-term response information to facilitate adaptive randomization for survival clinical trials
    Xuelin Huang
    Department of Biostatistics, The University of Texas, M D Anderson Cancer Center, Houston, TX 77030, U S A
    Stat Med 28:1680-9. 2009
    ..The new design uses fewer patients, and can more effectively assign patients to the better treatment arms. We demonstrate these properties through simulation studies...
  80. pmc Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters
    Lanlan Shen
    Department of Leukemia, The University of Texas at M D Anderson Cancer Center, Houston, Texas, USA
    PLoS Genet 3:2023-36. 2007
    ....
  81. pmc High-throughput methylation profiling by MCA coupled to CpG island microarray
    Marcos R H Estecio
    Department of Leukemia, UT M D Anderson Cancer Center, Houston, Texas 77030, USA
    Genome Res 17:1529-36. 2007
    ..In summary, MCAM is a suitable technique to discover methylated genes and to profile methylation changes in clinical samples in a high-throughput fashion...
  82. ncbi Methylation and regulation of expression of different retinoic acid receptor beta isoforms in human colon cancer
    Emile M Youssef
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Biol Ther 3:82-6. 2004
    ....
  83. ncbi Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel
    Lanlan Shen
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 67:11335-43. 2007
    ..Our results confirm that epigenetic profiles are useful in identifying molecular mediators for cancer drug sensitivity (pharmaco-epigenomics)...
  84. ncbi Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers
    Emile M Youssef
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 64:2411-7. 2004
    ..These findings indicate that silencing of TIG1 promoter by hypermethylation is common in human cancers and may contribute to the loss of retinoic acid responsiveness in some neoplastic cells...
  85. ncbi Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia
    Hagop Kantarjian
    Department of Leukemia, MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX 77030, USA
    Blood 109:52-7. 2007
    ..We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS...
  86. ncbi DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia
    Guillermo Garcia-Manero
    Departments of Leukemia, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 8:2217-24. 2002
    ..Aberrant methylation of promoter-associated CpG islands is an epigenetic oncogenic mechanism. The objective of this study was to define the methylation characteristics of patients with acute lymphocytic leukemia (ALL)...
  87. ncbi Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 106:1794-803. 2006
    ..Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters...
  88. ncbi Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia
    Guillermo Garcia-Manero
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 97:695-702. 2003
    ..This epigenetic modification has been associated with gene silencing, malignant transformation, and aging. It is not known whether there are epigenetic differences between pediatric patients and adult patients with ALL...
  89. ncbi Decitabine dosing schedules
    Hagop M Kantarjian
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Semin Hematol 42:S17-22. 2005
    ..Even with all the information we have learned, there is still a need to determine the optimal dosing schedule and the development of alternative dosing forms...
  90. ncbi Mitoxantrone: a hypomethylating agent?
    Allen S Yang
    Department of Leukemia, University of Texas at M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Biol Ther 2:264-5. 2003
  91. ncbi Association of the CpG island methylator phenotype with family history of cancer in patients with colorectal cancer
    Marsha L Frazier
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 63:4805-8. 2003
    ..Patients with methylation at all four loci were 14 times more likely to have a family history of cancer than patients with methylation at none of the four loci. These findings suggest that there may be a genetic component to CIMP in CRC...
  92. ncbi Regulation of RARbeta1 expression in head and neck cancer cells by cell density-dependent chromatin remodeling
    Emile M Youssef
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Cancer Biol Ther 3:1002-6. 2004
    ..These findings reveal that the expression of RARbeta1 is regulated by cell density through changes in histone acetylation...
  93. ncbi Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results
    Hagop M Kantarjian
    Departments of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 8:2177-87. 2002
    ..We identified pretreatment and treatment-associated factors that were associated with higher major cytogenetic response rates and with improved survival...
  94. ncbi Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate
    Hagop M Kantarjian
    Departments of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 8:2167-76. 2002
    ..Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has shown encouraging activity in chronic myelogenous leukemia (CML)...
  95. pmc JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia
    Jaroslav Jelinek
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA
    Blood 106:3370-3. 2005
    ..We conclude that the JAK2 1849G>T mutation is common in Ph(-) MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias...
  96. ncbi DNA methylation patterns at relapse in adult acute lymphocytic leukemia
    Guillermo Garcia-Manero
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Clin Cancer Res 8:1897-903. 2002
    ..To study the role of DNA methylation in relapse mechanisms in acute lymphocytic leukemia (ALL), we have compared the methylation status of five genes at the time of initial presentation and at first relapse in 25 adult patients with ALL...
  97. ncbi Optimizing annealing temperature overcomes bias in bisulfite PCR methylation analysis
    Lanlan Shen
    Department of Leukemia, M D Anderson Cancer Center, Houston, TX 77030, USA
    Biotechniques 42:48, 50, 52 passim. 2007
  98. ncbi DNA methylation and environmental exposures in human hepatocellular carcinoma
    Lanlan Shen
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, 77030, USA
    J Natl Cancer Inst 94:755-61. 2002
    ..To determine whether CIMP is associated with the development of hepatocellular carcinoma (HCC) and with exposure to environmental agents, we examined the methylation status of CpG islands in HCCs from countries with various HCC risks...
  99. pmc Concordant CpG island methylation in hyperplastic polyposis
    Annie On On Chan
    Department of Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 4095, USA
    Am J Pathol 160:529-36. 2002
    ..The hypermethylator phenotype is related to patient-specific factors, such as carcinogenic exposure or genetic predisposition...
  100. ncbi Methylated CpG island amplification for methylation analysis and cloning differentially methylated sequences
    Minoru Toyota
    Graduate School of Biomedical Sciences, MD Anderson Cancer Center, Houston, TX, USA
    Methods Mol Biol 200:101-10. 2002
  101. ncbi Effect of cytarabine and decitabine in combination in human leukemic cell lines
    Taichun Qin
    Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 13:4225-32. 2007
    ..5-Aza-2'-deoxycytidine (DAC) is a cytosine analogue that inhibits DNA methylation and also has activity in myeloid leukemia. Therefore, we investigated combining these two drugs in human leukemia cell lines in vitro...

Research Grants21

  1. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2001
    ..Ultimately, this work aims at establishing that methylation profiling may carry the same clinical implications as that already established for genetic profiling in neoplasia. ..
  2. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2006
    ..abstract_text> ..
  3. University of Texas M.D. Anderson Cancer SPORE-Leukemia
    Jean Pierre Issa; Fiscal Year: 2007
    ..Through this leukemia SPORE, our research team will make a significant impact on leukemia prognosis. ..
  4. Randomized study of combined epigenetic therapy
    Jean Pierre Issa; Fiscal Year: 2007
    ..This grant will support the first testing, in a randomized setting, of combined epigenetic therapy, with both molecular and clinical endpoints. ..
  5. Randomized study of combined epigenetic therapy
    Jean Pierre Issa; Fiscal Year: 2009
    ..This grant will support the first testing, in a randomized setting, of combined epigenetic therapy, with both molecular and clinical endpoints. ..
  6. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2007
    ..abstract_text> ..
  7. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2007
    ..These studies should provide definitive information on interactions between diet and DNA methylation in human colorectal mucosa and cancer. ..
  8. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2006
    ..abstract_text> ..
  9. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2002
    ..Ultimately, this work aims at establishing that methylation profiling may carry the same clinical implications as that already established for genetic profiling in neoplasia. ..
  10. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2003
    ..Ultimately, this work aims at establishing that methylation profiling may carry the same clinical implications as that already established for genetic profiling in neoplasia. ..
  11. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2004
    ..These studies should provide definitive information on interactions between diet and DNA methylation in human colorectal mucosa and cancer. ..
  12. Neoplasia and Methylated CpG Islands Amplification
    Jean Pierre Issa; Fiscal Year: 2004
    ..Ultimately, methylation profiling may prove very valuable in identifying subsets of patients with distinct clinical courses and response to specific therapeutic interventions, including using methylation inhibitors. ..
  13. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2004
    ..abstract_text> ..
  14. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2005
    ..These studies should provide definitive information on interactions between diet and DNA methylation in human colorectal mucosa and cancer. ..
  15. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2005
    ..abstract_text> ..
  16. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2006
    ..These studies should provide definitive information on interactions between diet and DNA methylation in human colorectal mucosa and cancer. ..
  17. Randomized study of combined epigenetic therapy
    Jean Pierre J Issa; Fiscal Year: 2010
    ..This grant will support the first testing, in a randomized setting, of combined epigenetic therapy, with both molecular and clinical endpoints. ..