Genomes and Genes
Summary: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
Publications309 found, 100 shown here
- Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cellsHsing Chen Tsai
The Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Cancer Cell 21:430-46. 2012..The DNA methylation inhibitors decitabine and azacitidine are efficacious for hematological neoplasms at lower, less toxic, doses...
- Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cellsYoshimasa Saito
Department of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA
Cancer Cell 9:435-43. 2006..These results suggest that DNA demethylation and histone deacetylase inhibition can activate expression of miRNAs that may act as tumor suppressors...
- Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancerRosalyn A Juergens
Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21231, USA
Cancer Discov 1:598-607. 2011..We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively ..
- Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III studyPierre Fenaux
Hopital Avicenne, Universite Paris XIII, Bobigny, France
Lancet Oncol 10:223-32. 2009..In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens.
- Gene reactivation by 5-aza-2'-deoxycytidine-induced demethylation requires SRCAP-mediated H2A.Z insertion to establish nucleosome depleted regionsXiaojing Yang
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS Genet 8:e1002604. 2012..Furthermore, we elucidate that chromatin remodeling translates the demethylation ability of DNMT inhibitors to their downstream efficacies, suggesting future therapeutic implications for chromatin remodelers...
- 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapyJudith K Christman
Department of Biochemistry and Molecular Biology and UNMC Eppley Cancer Center, University of Nebraska Medical Center, 984525 University Medical Center, Omaha, Nebraska, NE 68198 4525, USA
Oncogene 21:5483-95. 2002..The implications of these mechanistic studies for development of less toxic inhibitors of DNA methylation are discussed...
- Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancerU Lehmann
Institute of Pathology, Medizinische Hochschule Hannover, Carl Neuberg Strasse 1, D 30625, Hannover, Germany
J Pathol 214:17-24. 2008..8). In conclusion, this study demonstrates that various microRNA genes are also affected by epigenetic inactivation due to aberrant hypermethylation and that this is an early and frequent event in breast cancer development...
- Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignanciesJean 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...
- Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemiaWilliam Blum
Department of Medicine, Division of Hematology and Oncology, The Ohio State University, Columbus, OH 43210, USA
J Clin Oncol 25:3884-91. 2007..To determine an optimal biologic dose (OBD) of decitabine as a single agent and then the maximum-tolerated dose (MTD) of valproic acid (VA) combined with decitabine in acute myeloid leukemia (AML)...
- Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized studyHagop 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...
- Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabineCarlo Stresemann
Division of Epigenetics, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
Int J Cancer 123:8-13. 2008..We also discuss the mechanism of DNA methyltransferase inhibition and emphasize the need for the identification of predictive biomarkers for the further advancement of epigenetic therapies...
- Epigenetic regulation of microRNA expression in colorectal cancerEva Bandres
Division of Oncology, Laboratory of Pharmacogenomics, Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Navarra, Spain
Int J Cancer 125:2737-43. 2009..In summary, our results aid in the understanding of miRNA gene regulation showing that aberrant DNA methylation and histone modifications work together to induce silencing of miRNAs in CRC...
- 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signalKalpana Ghoshal
Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
Mol Cell Biol 25:4727-41. 2005..These results demonstrate a unique mechanism for the selective degradation of DNMT1, the maintenance DNA methyltransferase, by well-known DNA-hypomethylating agents...
- Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancerO Aguilera
Instituto de Investigaciones Biomédicas Alberto Sols and Departamento de Bioquímica, Facultad de Medicina, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Madrid, Spain
Oncogene 25:4116-21. 2006....
- RNA-dependent inhibition of ribonucleotide reductase is a major pathway for 5-azacytidine activity in acute myeloid leukemiaJosephine Aimiuwu
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
Blood 119:5229-38. 2012..In conclusion, we identify RRM2 as a novel molecular target of 5-azaC in AML. Our findings provide a basis for its more widespread clinical use either alone or in combination...
- Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemiasR Itzykson
Service d Hématologie Clinique Hôpital Avicenne, Assistance Publique Hopitaux de Paris AP HP, Universite Paris 13, Bobigny, France
Leukemia 25:1147-52. 2011The impact of ten-eleven-translocation 2 (TET2) mutations on response to azacitidine (AZA) in MDS has not been reported...
- Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemiaPierre Fenaux
Service d Hematologie Clinique, Hospital Avicenne, Assistance Publique Hopitaux de Paris AP HP, Universite Paris XIII, Bobigny, France
J Clin Oncol 28:562-9. 2010In a phase III randomized trial, azacitidine significantly prolonged overall survival (OS) compared with conventional care regimens (CCRs) in patients with intermediate-2- and high-risk myelodysplastic syndromes...
- Functional diversity of DNA methyltransferase inhibitors in human cancer cell linesCarlo Stresemann
Division of Epigenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Cancer Res 66:2794-800. 2006..These results show a substantial diversity in the molecular activities of DNA methyltransferase inhibitors and provide valuable insights into the developmental potential of individual drugs...
- Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persistsDavid Mossman
Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia
BMC Cancer 10:366. 2010..We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes...
- Targeting DNA methylation for epigenetic therapyXiaojing Yang
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Trends Pharmacol Sci 31:536-46. 2010..This review delineates the latest cancer epigenetic models, the recent discovery of hypomethylation agents as well as their application in the clinic...
- Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soyMing Zhu Fang
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 8020, USA
Clin Cancer Res 11:7033-41. 2005..To determine whether other polyphenolic compounds have similar activities, we studied the effects of soy isoflavones on DNA methylation...
- Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidineRaphael Itzykson
Clinique Hôpital Avicenne, Assistance Publique Hopitaux de Paris, Paris, France
Blood 117:403-11. 2011Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown...
- DNA methylation as a therapeutic target in cancerJean 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...
- Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2'-deoxycytidineCarvell T Nguyen
Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center and Hospital, University of Southern California, Keck School of Medicine, Los Angeles, California 90089, USA
Cancer Res 62:6456-61. 2002..In addition, 5-Aza-CdR increased acetylation and H3-K4 methylation at the unmethylated p14 promoter, suggesting it can induce chromatin remodeling independently of its effects on cytosine methylation...
- Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cellsX Yang
The Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231, USA
Cancer Res 61:7025-9. 2001..These data suggest that the activities of both DNMT1 and HDAC are key regulators of methylation-mediated ER gene silencing...
- Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndromeAndres O Soriano
Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
Blood 110:2302-8. 2007..We conducted a phase 1/2 study of the combination of 5-azacitidine (5-AZA), valproic acid (VPA), and ATRA in patients with acute myeloid leukemia or high-risk myelodysplastic ..
- In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemiaJaebok Choi
Division of Oncology, Department of Medicine, Washington University, St Louis, MO 63110, USA
Blood 116:129-39. 2010..Here, we show that the FDA-approved hypomethylating agents, decitabine (Dec) and azacitidine (AzaC), induce FOXP3 expression in CD4(+)CD25(-) T cells both in vitro and in vivo...
- Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)Oliver C Goodyear
School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom
Blood 119:3361-9. 2012..b>Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of ..
- MDS and secondary AML display unique patterns and abundance of aberrant DNA methylationMaria E Figueroa
Department of Medicine Hematology Oncology Division, Weill Cornell Medical College, New York, NY 10065, USA
Blood 114:3448-58. 2009..This trial was registered at www.clinicaltrials.gov as J0443...
- Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndromeEmmanuel Raffoux
Departement d Hematologie, Hopital Saint Louis, Assistance Publique Hopitaux de Paris, and Université Denis Diderot Paris 7, EA 3518, Institut Universitaire d Hematologie, Paris
Oncotarget 1:34-42. 2010In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)...
- Targeting of 5-aza-2'-deoxycytidine residues by chromatin-associated DNMT1 induces proteasomal degradation of the free enzymeKatan Patel
Breakthrough Research Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Nucleic Acids Res 38:4313-24. 2010..The proteasome inhibitor MG132 prevents DNMT1 degradation and reduces hypomethylation induced by 5-aza-dC...
- Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine*Valeria Santini
Azienda Ospedaliera Universitaria Careggi, Florence, Italy
Eur J Haematol 85:130-8. 2010..We present previously unpublished data from two large phase III trials describing common adverse events (AEs) associated with azacitidine and methods to manage them.
- DNA methylation changes after 5-aza-2'-deoxycytidine therapy in patients with leukemiaAllen S Yang
Department of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Cancer Res 66:5495-503. 2006..In conclusion, we show dose-dependent hypomethylation after decitabine at low doses. Increasing the dose, which has been shown previously to result in a reduced response rate, was not accompanied by further hypomethylation...
- DNA methylation changes following 5-azacitidine treatment in patients with myelodysplastic syndromeHuong Thi Thanh Tran
Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Korea
J Korean Med Sci 26:207-13. 2011DNA methyltransferase inhibitor, 5-azacitidine (AC) is effective in myelodysplastic syndromes (MDS) and can induce re-expression in cancer. We analyzed the methylation of 25 tumor suppressor genes in AC-treated MDS...
- Integrative analysis of epigenetic modulation in melanoma cell response to decitabine: clinical implicationsRuth Halaban
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, United States of America
PLoS ONE 4:e4563. 2009..Our integrative analysis show that improved therapy can be achieved by comprehensive analysis of cancer cells, identified biomarkers for patient's selection and monitoring response, as well as targets for improved combination therapy...
- Antimitogenic and chemosensitizing effects of the methylation inhibitor zebularine in ovarian cancerCurtis Balch
Medical Sciences Program, Indiana University, 302 Jordan Hall, 1001 East Third Street, Bloomington, IN 47405, USA
Mol Cancer Ther 4:1505-14. 2005..In summary, zebularine seems to be a promising clinical candidate, singly or combined with conventional regimens, for the therapy of drug-resistant ovarian cancer...
- Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for ReseMichael Lubbert
Albert Ludwigs University, Freiburg, Germany
J Clin Oncol 29:1987-96. 2011..To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy...
- Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failureThomas Prebet
Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA
J Clin Oncol 29:3322-7. 2011b>Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure...
- A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell linesPaul W Hollenbach
Celgene Corporation, San Francisco, California, United States of America
PLoS ONE 5:e9001. 2010The cytidine nucleoside analogs azacitidine (AZA) and decitabine (DAC) are used for the treatment of patients with myelodysplastic syndromes and acute myeloid leukemia (AML)...
- GSTP1 DNA methylation and expression status is indicative of 5-aza-2'-deoxycytidine efficacy in human prostate cancer cellsKaren Chiam
Dame Roma Mitchell Cancer Research Laboratories, Discipline of Medicine, University of Adelaide, Hanson Institute, Adelaide, Australia
PLoS ONE 6:e25634. 2011..We conclude that the DNA methylation and protein expression status of GSTP1 are good indicators of DNMTi efficacy...
- Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapyHagop M Kantarjian
Leukemia Department, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Blood 116:3163-70. 2010..a thrombopoietin mimetic, in patients with low- or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine therapy...
- A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elementsAllen 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...
- The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cellsC Flotho
Division of Pediatric Hematology Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany
Leukemia 23:1019-28. 2009The three DNA methyltransferase (DNMT)-inhibiting cytosine nucleoside analogues, azacitidine, decitabine and zebularine, which are currently studied as nonintensive therapy for myelodysplastic syndromes and acute myeloid leukemia (AML), ..
- Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumorsJoo Mi Yi
Cancer Biology Division, Johns Hopkins Kimmel Cancer Center, USA
Cancer Res 68:8094-103. 2008..Our findings provide additional insight for the dynamics of aberrant DNA methylation associated with aberrant gene silencing in human tumors...
- Phase I study of decitabine-mediated gene expression in patients with cancers involving the lungs, esophagus, or pleuraDavid S Schrump
Thoracic Oncology Section Surgery Branch, Cancer Therapy Evaluation Program, National Cancer Institute NIH, 10 Center Drive, Bethesda, MD 20892, USA
Clin Cancer Res 12:5777-85. 2006..A phase I trial was done to examine pharmacokinetics, toxicities, and gene expression mediated by 5-aza-2'-deoxycytidine (DAC) in patients with thoracic malignancies...
- BCL2L10 is a predictive factor for resistance to azacitidine in MDS and AML patientsThomas Cluzeau
INSERM U1065, Centre Méditerranéen de Médecine Moléculaire, Team Cell Death, Differentiation, Inflammation and Cancer, Nice, France
Oncotarget 3:490-501. 2012b>Azacitidine is the leading compound to treat patients suffering myelodysplastic syndrome (MDS) or AML with less than 30% of blasts, but a majority of patients is primary refractory or rapidly relapses under treatment...
- 5-Aza-cytidine is a potent inhibitor of DNA methyltransferase 3a and induces apoptosis in HCT-116 colon cancer cells via Gadd45- and p53-dependent mechanismsRegine Schneider-Stock
Department of Pathology, Division Molecular Genetics, Otto von Guericke University, Leipziger Str 44, 39120 Magdeburg, Germany
J Pharmacol Exp Ther 312:525-36. 2005..Our data demonstrate that 5-aza-CR action in HCT-116 is mediated by p53 and its downstream effectors p21(WAF1) and GADD45. This is the first report to show a link between p53 and regulation of DNMT1 and de novo methyltransferase DNMT3a...
- Decitabine and suberoylanilide hydroxamic acid (SAHA) inhibit growth of ovarian cancer cell lines and xenografts while inducing expression of imprinted tumor suppressor genes, apoptosis, G2/M arrest, and autophagyMin Yu Chen
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Cancer 117:4424-38. 2011..In this study, demethylating agents and HDAC inhibitors were tested for their ability to induce re-expression of tumor suppressor genes, inhibiting growth of ovarian cancer cells in culture and in xenografts...
- Azacytidine and decitabine induce gene-specific and non-random DNA demethylation in human cancer cell linesSabine Hagemann
Division of Epigenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany
PLoS ONE 6:e17388. 2011..Our results provide detailed insights into the DNA methylation patterns induced by azacytidine and decitabine and suggest the involvement of complex regulatory mechanisms in drug-induced DNA demethylation...
- Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasiaOliver Goodyear
CRUK Institute for Cancer Studies, University of Birmingham, Birmingham
Blood 116:1908-18. 2010..In this study, we demonstrate that azacitidine (AZA) and sodium valproate (VPA) up-regulate expression of melanoma-associated antigens (MAGE antigens) on ..
- DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3BStela S Palii
Department of Biochemistry and Molecular Biology, University of Florida, College of Medicine, Box 100245, 1600 SW Archer Rd, Gainesville, FL 32610, USA
Mol Cell Biol 28:752-71. 2008....
- Chromatin remodeling is required for gene reactivation after decitabine-mediated DNA hypomethylationJiali Si
Department of Leukemia, The University of Texas M D Anderson Cancer Center, TX, USA
Cancer Res 70:6968-77. 2010..Our findings suggest that gene expression is the key in optimizing DAC treatment strategies in the clinic...
- Identification of novel target genes by an epigenetic reactivation screen of renal cancerInmaculada Ibanez de Caceres
Departments of Surgical Oncology and Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Cancer Res 66:5021-8. 2006....
- Human bone marrow stem cells co-cultured with neonatal rat cardiomyocytes display limited cardiomyogenic plasticityRemco Koninckx
Laboratory of Experimental Hematology, Virga Jesse Hospital, Hasselt, Belgium
Cytotherapy 11:778-92. 2009..Stem cells were obtained from patients with ischemic heart disease...
- p53-inducible ribonucleotide reductase (p53R2/RRM2B) is a DNA hypomethylation-independent decitabine gene target that correlates with clinical response in myelodysplastic syndrome/acute myelogenous leukemiaPetra A Link
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
Cancer Res 68:9358-66. 2008..0047) between p53R2 mRNA induction and clinical response in MDS/AML. These data establish p53R2 as a novel hypomethylation-independent decitabine gene target associated with clinical response...
- Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylationMaria Rius
Division of Tumor Biochemistry, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
Mol Cancer Ther 8:225-31. 2009..In conclusion, our study identifies 5-azaCyd as a novel substrate for hCNT1 and provides direct evidence that hCNT1 is involved in the DNA-demethylating effects of this drug...
- Evaluation of a 7-day continuous intravenous infusion of decitabine: inhibition of promoter-specific and global genomic DNA methylationWolfram E Samlowski
Huntsman Cancer Institute and the Department of Internal Medicine Oncology, University of Utah, Salt Lake City, UT 84112 5550, USA
J Clin Oncol 23:3897-905. 2005..A clinical study was designed to examine the molecular effects and toxicity of a continuous 1-week intravenous infusion of decitabine in solid tumor patients...
- 5-Aza-2'-deoxycytidine (decitabine) can relieve p21WAF1 repression in human acute myeloid leukemia by a mechanism involving release of histone deacetylase 1 (HDAC1) without requiring p21WAF1 promoter demethylationStuart A Scott
Department of Pathology, University of Saskatchewan, Saskatoon Cancer Centre, 20 Campus Drive, Saskatoon, Saskatchewan, Canada
Leuk Res 30:69-76. 2006..This latter finding is of relevance to the clinical use of these agents in AML as we found the p21WAF1 promoter to be unmethylated in vivo...
- SLIT2 attenuation during lung cancer progression deregulates beta-catenin and E-cadherin and associates with poor prognosisRuo Chia Tseng
Institute of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China
Cancer Res 70:543-51. 2010..Our findings indicate that SLIT2 suppresses lung cancer progression, defining it as a novel "theranostic" factor with potential as a therapeutic target and prognostic predictor in lung cancer. Cancer Res; 70(2); 543-51...
- Intratracheally administered 5-azacytidine is effective against orthotopic human lung cancer xenograft models and devoid of important systemic toxicitySameer Mahesh
Department of Medicine, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Clin Lung Cancer 11:405-11. 2010..The purpose of this study is to explore the therapeutic potential of regional administration (via the airways) of the demethylating agent 5-azacytidine (5-Aza) for the treatment of early lung cancer...
- The depletion of DNA methyltransferase-1 and the epigenetic effects of 5-aza-2'deoxycytidine (decitabine) are differentially regulated by cell cycle progressionMazin Al-Salihi
Protein Phosphorylation Unit, Medical Research Council Dundee, Scotland
Epigenetics 6:1021-8. 2011....
- Functional DNA demethylation is accompanied by chromatin accessibilityKurinji Pandiyan
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 USA
Nucleic Acids Res 41:3973-85. 2013....
- Azacitidine for the treatment of patients with acute myeloid leukemia: report of 82 patients enrolled in an Italian Compassionate ProgramLuca Maurillo
Institute of Hematology, Tor Vergata Foundation Polyclinic, Rome, Italy
Cancer 118:1014-22. 2012The efficacy of azacitidine for the treatment of high-risk myelodysplastic syndromes has prompted the issue of its potential role even in the treatment of acute myeloid leukemia (AML).
- 5-Azacytidine supports the long-term repopulating activity of cord blood CD34(+) cellsMotoyuki Suzuki
Fujisaki Cell Center, Hayashibara Biochemical Laboratories, Inc, Okayama, Japan
Am J Hematol 77:313-5. 2004..These results indicated the involvement of DNA methylation and demethylation in controlling immaturity of hematopoietic progenitor cells and the usefulness of 5-AzaC for regulating this immaturity...
- DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitorsW G Zhu
Department of Internal Medicine and the Comprehensive Cancer Center, The Ohio State University, Columbus 43210-1240, USA
Cancer Res 61:1327-33. 2001..These results demonstrate that DNA methylation status is an important determinant of apoptotic susceptibility to HDAC inhibitors...
- The absence of p53 is critical for the induction of apoptosis by 5-aza-2'-deoxycytidineMaria Nieto
Department of Immunology and Oncology, Spanish National Center of Biotechnology CNB, Madrid, Spain
Oncogene 23:735-43. 2004..Together, our results put forward the hypothesis that the absence of p53 may determine a higher chemotherapeutic index for 5-aza-dC...
- Role of the DNA methyltransferase variant DNMT3b3 in DNA methylationDaniel J Weisenberger
Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089 9181, USA
Mol Cancer Res 2:62-72. 2004..Methylation analyses of immunodeficiency, chromosomal instabilities, and facial abnormalities cells revealed that an Alu repeat sequence was highly methylated, suggesting that Alu sequences are not DNMT3b targets...
- Effects of 5-aza-2'-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell diseaseYogen Saunthararajah
University of Illinois at Chicago, Section of Hem Onc, MBRB Rm 3150 MC734, 900 S Ashland Ave, Chicago, IL 60607, USA
Blood 102:3865-70. 2003..Chronic dosing and sustained increases in hemoglobin F and total hemoglobin levels may be possible. Further studies in SSD and thalassemia are indicated...
- Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemiaD A Pollyea
Division of Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO 80045, USA
Leukemia 26:893-901. 2012..In this phase-1 study, we determined the maximum tolerated dose (MTD) and the efficacy for sequential azacitidine and lenalidomide as remission induction and continuation therapy in elderly, previously untreated patients...
- Effect of CpG island methylation on microRNA expression in the k-562 cell lineYang Yang
Department of Hematology and BMT Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
Biochem Genet 50:122-34. 2012..Expression levels of miR-369, miR-615, and miR-410 were not regulated by DNA methylation in this cell line...
- Genome-wide methylation profiling in decitabine-treated patients with acute myeloid leukemiaPearlly Yan
Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, 460 W 12th Ave, Columbus, OH 43210, USA
Blood 120:2466-74. 2012..Decitabine-related methylation changes were concordant with those previously reported in distinct genes. In summary, our study supports the feasibility of methylome analyses as a pharmacodynamic endpoint for hypomethylating therapies...
- Therapy with azanucleosides for myelodysplastic syndromesAlfonso Quintas-Cardama
Department of Leukemia, The University of Texas, M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Nat Rev Clin Oncol 7:433-44. 2010..Two agents, 5-azacitidine and decitabine, have been approved by the FDA for treatment of MDS...
- The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastomaAnna Djos
Department of Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, SE 413 45, Gothenburg, Sweden
Mol Cancer 11:40. 2012..Data from our previously performed genome-wide DNA methylation array analysis indicated that other members of the RASSF gene family are targeted by DNA methylation in neuroblastoma...
- Azacitidine-resistant SKM1 myeloid cells are defective for AZA-induced mitochondrial apoptosis and autophagyThomas Cluzeau
Cell Death, Differentiation, Inflammation and Cancer Team, INSERM U895, Nice, France
Cell Cycle 10:2339-43. 2011b>Azacitidine (AZA) is the current treatment for patients with high-risk myelodysplastic syndrome, but resistance is a common feature of AZA-treated patients...
- Activity of azacitidine in chronic myelomonocytic leukemiaRubens Costa
Division of Hematology Oncology, Western Pennsylvania Cancer Institute, Western Pennsylvania Hospital, Pittsburgh, PA 15224, USA
Cancer 117:2690-6. 2011Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML)...
- Decitabine maintains hematopoietic precursor self-renewal by preventing repression of stem cell genes by a differentiation-inducing stimulusZhenbo Hu
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
Mol Cancer Ther 9:1536-43. 2010..Using decitabine to deplete DNMT1 after this early repression phase does not impair progressive differentiation...
- Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromesLewis R Silverman
Department of Medicine Oncology, Mount Sinai School of Medicine, New York, NY 10029, USA
Cancer 117:2697-702. 2011In the AZA-001 trial, azacitidine (75 mg/m(2) /d subcutaneously for Days 1-7 of every 28-day cycle) demonstrated improved survival compared with conventional care regimens in patients with International Prognostic Scoring System-defined ..
- p53 independent epigenetic-differentiation treatment in xenotransplant models of acute myeloid leukemiaK P Ng
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA
Leukemia 25:1739-50. 2011..Modifying in vivo dose and schedule to emphasize this pathway of decitabine action can bypass a mechanism of resistance to standard therapy...
- Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineeringK Fukuda
Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan
Artif Organs 25:187-93. 2001..These cells expressed Nkx2.5, GATA4, TEF-1, and MEF2-C mRNA before 5-azacytidine treatment, and expressed MEF2-A and MEF2-D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte transplantation...
- Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trialU Platzbecker
Medical Clinic and Polyclinic I, University Hospital Carl Gustav Carus Technical University of Dresden, Dresden, Germany
Leukemia 26:381-9. 2012This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34(+) blood cells to pre-empt relapse in patients with CD34(+) myelodysplastic syndromes (MDS) or ..
- Decitabine and vorinostat cooperate to sensitize colon carcinoma cells to Fas ligand-induced apoptosis in vitro and tumor suppression in vivoDafeng Yang
Department of Biochemistry and Molecular Biology, Georgia Health Sciences University, Augusta, GA 30912, USA
J Immunol 188:4441-9. 2012..Thus, our data suggest that combined modalities of chemotherapy to sensitize the tumor cell to Fas-mediated apoptosis and CTL immunotherapy is an effective approach for the suppression of colon cancer metastasis...
- Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemiaWilliam Blum
Division of Hematology, Department of Medicine, The Ohio State University Comprehensive Cancer Center, B310 Starling Loving Hall, Columbus, OH 43210, USA
Blood 119:6025-31. 2012..This study demonstrates the feasibility and preliminary clinical activity of decitabine plus bortezomib in AML and identifies FLT3 as a novel pharmacodynamic end point for future trials...
- Increased PRAME antigen-specific killing of malignant cell lines by low avidity CTL clones, following treatment with 5-Aza-2'-DeoxycytidineMengyong Yan
Unit of Molecular Haematology and Cancer Biology, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
Cancer Immunol Immunother 60:1243-55. 2011..Together these data point to a general increased augmentation of cancer immunogenocity by DAC involving both antigen-specific and non-specific mechanisms...
- Pretreatment of rat bone marrow mesenchymal stem cells with a combination of hypergravity and 5-azacytidine enhances therapeutic efficacy for myocardial infarctionShu Kuan Ling
Department of Life Science and Engineering, Harbin Institute of Technology, Harbin 150001, China
Biotechnol Prog 27:473-82. 2011....
- Noncytotoxic differentiation treatment of renal cell cancerSoledad Negrotto
Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
Cancer Res 71:1431-41. 2011..The distinctive mechanism of action of a dose and schedule of DAC designed for noncytotoxic depletion of DNMT1 suggests a potential role in treating RCC...
- Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AMLJoseph M Scandura
Leukemia Program, Weill Cornell Medical College, New York, NY, USA
Blood 118:1472-80. 2011..We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876...
- Hypomethylating agents and other novel strategies in myelodysplastic syndromesGuillermo Garcia-Manero
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Box 428, 1515 Holcombe Blvd, PO Box 301402, Houston, TX 77025, USA
J Clin Oncol 29:516-23. 2011..Treatment options for patients with higher-risk MDS include hypomethylating agents (azacitidine and decitabine), intensive chemotherapy (ICT), and allogeneic stem-cell transplantation (alloSCT)...
- Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding studyMarcos de Lima
Department of Stem Cell Transplantation and Cell Therapy, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Cancer 116:5420-31. 2010..b>Azacitidine is a DNA methyltransferase inhibitor with activity in myeloid disease...
- Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: azacitidine compared with low dose ara-CPierre Fenaux
Hopital Avicenne, Assistance Publique Hôpitaux de Paris and Paris 13 University, Bobigny, France
Br J Haematol 149:244-9. 2010..MDS) who are ineligible for intensive treatment, was found to be associated with poorer survival compared with azacitidine. This analysis further compared the efficacy and the toxicity of these two drug regimens...
- Regulation of human endogenous retrovirus-K expression in melanomas by CpG methylationSven Stengel
Retrovirus Induced Immunosuppression, Robert Koch Institute, Nordufer 20, Berlin, Germany
Genes Chromosomes Cancer 49:401-11. 2010..These results demonstrate that increased HERV-K expression in melanomas may be due to increased promoter activity and demethylation of the 5'LTR...
- Pharmacokinetics of 5-azacitidine administered with phenylbutyrate in patients with refractory solid tumors or hematologic malignanciesMichelle A Rudek
Division of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
J Clin Oncol 23:3906-11. 2005To characterize the pharmacokinetic behavior of 5-azacitidine (5-AC), a cytidine nucleoside analog, when given with phenylbutyrate, a histone deaceytlase inhibitor.
- Chromatin-modifying agents permit human hematopoietic stem cells to undergo multiple cell divisions while retaining their repopulating potentialHiroto Araki
Section of Hematology Oncology, Department of Medicine, University of Illinois at Chicago, 909 S Wolcott Avenue, Chicago, IL 60612, USA
Blood 109:3570-8. 2007..These data indicate that HSC treated with chromatin-modifying agents are capable of undergoing repeated cell divisions in vitro while retaining their marrow-repopulating potential...
- High-resolution mapping of DNA methylation in human genome using oligonucleotide tiling arrayHiroshi Hayashi
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4 6 1 Komaba, Meguro ku, Tokyo, Japan
Hum Genet 120:701-11. 2007..Our method recognizes DNA methylation with little bias by genomic location and, therefore, is useful for comprehensive high-resolution analysis of DNA methylation providing new findings in the epigenomics...
- Pharmacology of 5-Aza-2'-deoxycytidine (decitabine)Richard L Momparler
Centre de Recherche, Hopital Sainte Justine, Montreal, Quebec, Canada
Semin Hematol 42:S9-16. 2005..Translation of the pharmacology of 5AZA-CdR into therapeutic regimens based on scientific rationale can be used to obtain this objective...
- Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancersEmile 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...
- 5-Azacytidine induced methyltransferase-DNA adducts block DNA replication in vivoH Kenny Kuo
Department of Biochemistry, Duke University, Durham, NC 27710, USA
Cancer Res 67:8248-54. 2007..Such replication-dependent DNA breaks may represent an important pathway that contributes to genome rearrangement and/or cytotoxicity...
- Global demethylation of rat chondrosarcoma cells after treatment with 5-aza-2'-deoxycytidine results in increased tumorigenicityChristopher A Hamm
Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, United States of America
PLoS ONE 4:e8340. 2009..Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells...
- Epigenetic inactivation of the miR-124-1 in haematological malignanciesKwan Yeung Wong
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
PLoS ONE 6:e19027. 2011..Amongst haematological cancers, miR-124-1 was more frequently hypermethylated in NHL, and hence warrants further study...
- De novo induction of a cancer/testis antigen by 5-aza-2'-deoxycytidine augments adoptive immunotherapy in a murine tumor modelZ Sheng Guo
Thoracic Oncology Section and Tumor Immunology Section, Surgery Branch, National Cancer Institute NIH, Bethesda, MD 20892, USA
Cancer Res 66:1105-13. 2006..These data show a novel strategy of combined chemoimmunotherapy of cancer targeting a CTA induced de novo in a broad range of tumor histologies, and support further evaluation of chromatin-remodeling agents for human cancer therapy...
- Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosusQianjin Lu
Cancer Center and Geriatric Center, University of Michigan, Ann Arbor, MI 48109, USA
Arthritis Rheum 46:1282-91. 2002..The present study investigated the nature of the methylation change that affects LFA-1 expression in vitro and in human lupus...
- A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradationJharna Datta
Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, OH 43210, USA
Cancer Res 69:4277-85. 2009..Further, this compound did not exhibit significant toxicity in a rat hepatoma (H4IIE) cell line. This study provides a novel class of DNA hypomethylating agents that have the potential for use in epigenetic cancer therapy...
- Reactivation of Fetal Gamma-globin Genes for the Treatment of Beta-globin DisordeOsamu Tanabe; Fiscal Year: 2010..abstract_text> ..
- Targeting aberrant epigenetics by nanomedicineShujun Liu; Fiscal Year: 2013..Inhibition of aberrant DNA methylation by decitabine or 5-azacitidine restores normal patterns of cell proliferation, differentiation and apoptosis, however, the clinical response ..
- Reactivation of Tumor Suppressor Genes in Breast Cancer by Dietary Supplements asZhongfa Liu; Fiscal Year: 2010..Reactivation of TSGs by azanucleoside DNA methylation inhibitors, such as decitabine and 5-azacitidine will result in restoration of their biological functions and represents a novel, superior chemotherapeutic ..
- Reprogramming of endothelial cells for improved cardiomyogenicity in vivoMELISSA ANN THAL; Fiscal Year: 2012..Most importantly, our results may significantly improve an existing cellular therapy and improve the lives of the over 16 million patients in the United States living with coronary heart disease. ..
- Processing and consequences of DNA-protein crosslinks in E. coliKenneth N Kreuzer; Fiscal Year: 2012..Aspects of this model will be tested, including the role of the site- specific crosslinks in triggering the tmRNA system and the fate of the RNA and RNA polymerase in the blocked complexes. ..
- The epigenetic basis of cytoplasmic incompatibilityKRISTIN KALIE JERNIGAN; Fiscal Year: 2012..This research will determine, for the first time, if Wolbachia induces an infectious epigenetic alteration to cause CI. ..
- Myelodysplastic Syndromes: Patterns of Care and OutcomesXiaomei Ma; Fiscal Year: 2010..diagnosis and the use of various treatment strategies, included the recently approved DNA demethylating agents, azacitidine and decitabine;(2) identify factors that influence the survival of MDS patients after accounting for comorbid ..
- in vivo Studies of Clinical Stage Globin ModulatorsSUSAN PARK PERRINE; Fiscal Year: 2011..The therapeutics are already approved for other conditions. Upon completion of the proposed studies, the most potent agent can be tested in the patient populations, and a new therapy can be rapidly applied to patient care. ..
- Phase I Clinical Trials of Anti-Cancer AgentsMark J Ratain; Fiscal Year: 2013..1) XK469 as a single dose every 3 weeks, 2) cilengitide by prolonged continuous infusion, 3) PXD101 and 5-azacitidine in leukemia, and 4) a randomized dose-escalation study of sorafenib using 12- hour ambulatory blood pressure ..
- Loss of miR-29s as predictor of response to demethylating agentsCarlo M Croce; Fiscal Year: 2010..We also intend to validate our hypothesis in mouse models. ..
- Comparative Effectiveness: Erythropoietic Stimulating Agents in Treatment of MDSAmy J Davidoff; Fiscal Year: 2010..High-risk MDS patients and those with poor or lapsed response to ESAs may receive 5 azacitidine or decitabine...
- Inhaled DNA demethylating therapy for lung cancer and bronchial premalignancyYiyu Zou; Fiscal Year: 2013..If successful, such intervention may postpone or effectively prevent the occurrence of lung cancer in the large population of individuals at risk. ..
- Targeting Epigenomics in Myeloid NeoplasmsSteven D Gore; Fiscal Year: 2013..The third aim will examine to what extent epigenetic modifications differ when the HDAC inhibitor is given concomitantly with the DNMT inhibitor versus sequential administration ..
- DE NOVO DNA METHYLATION IN BLADDER CANCERGANGNING NONE LIANG; Fiscal Year: 2013....
- ANTITUMOR DRUG EFFECTS ON PHOSPHATIDYLINOSITIDE TURNOVERJOHANNA STOECKLER; Fiscal Year: 1990..These studies may provide insights into the cytotoxic, differentiation-inducing and immunosuppressive effects of these antimetabolites and suggest ways to overcome host toxicities or enhance therapeutic efficacy...
- Epigenetic-based therapy of Hodgkin lymphomaAnas Younes; Fiscal Year: 2011..strategy using an isotype selective HDAC inhibitor MGCD0103 in combinafion with a hypomethylafing agent (azacitidine), and in the second we use the pan DAC inhibitor panobinostat (LBH589) in the same pafients populafion...
- ERYTHROPOIESIS AND HEMOGLOBIN REGULATION IN MANBLANCHE ALTER; Fiscal Year: 1990....
- HTLV-III SEQUENCES AT THE TRANSCRIPTIONAL LEVELJOSEPH MOSCA; Fiscal Year: 1991....
- TURNING SCAR INTO VIABLE MYOCARDIUMRace Kao; Fiscal Year: 2004..Success of this project may provide innovative approaches to treat myocardial infarction or cardio-myopathies associated with muscle cell loss and interstitial fibrosis. ..
- CDK INHIBITORS AND RESPONSE TO DHAC IN MESOTHELIOMARobert Kratzke; Fiscal Year: 2001..3) Response to azacytidine based therapy correlates with the presence of hypermethylation of the p16INK4a gene. 4) Response to azacytidine based therapy is inversely correlated with gene rearrangement of p16INK4a in mesothelioma tumors. ..
- Phase II trial of valproic acid in myelodysplasiaPeter Klein; Fiscal Year: 2006..VPA offers the significant advantages that it is a clinically well-characterized, relatively safe medication that can be administered orally and can be accurately monitored by well-established methods. ..
- DeNovo DNA Methyltransferases as Anticancer Drug TargetsJudith Christman; Fiscal Year: 2002..2) Use a novel SDS-PAGE gel assay that measures inhibitor binding affinity for DNMTs to predict the potency of a variety of new inhibitory targets for DNMTs 1, 3a and 3b. ..
- DNA METHYLATION, GENE EXPRESSION AND AUTOIMMUNITYBruce Richardson; Fiscal Year: 1992..These studies may help elucidate the pathogenesis of some forms of autoimmunity...
- REGULATION OF DEOXYCYTIDINE KINASE IN LEUKEMIC CELLSLANIER AYSCUE; Fiscal Year: 1999....
- THE ACTION OF ARA-C AND 5-AZA-C ON MEMBRANE SYNTHESISCAROLE JELSEMA; Fiscal Year: 1980..The present research proposes to examine the effect of these agents on membrane synthesis by in vitro enzyme assays, as well as morphologically, by autoradiography and electron microscopy. ..
- Regulation of Apical Polarity in Breast CancerSOPHIE LELIEVRE; Fiscal Year: 2006..unreadable] [unreadable] [unreadable]..
- Transcriptional Regulation in hMLH1-Silenced Colon CellsW Sedwick; Fiscal Year: 2007..2/3 of these MSI cancers are classified as cancers of sporadic origin because their occurrence does not correlate with a known familial defect. ..
- DEMETHYLATION THERAPY OF THYROID CARCINOMAKenneth Ain; Fiscal Year: 2004..Such patient-oriented research will proceed in the context of active mentorship in thyroid oncology and translational research centered on Oncology fellows. ..
- MECHANISM OF 5-AZACR-MEDIATED ALTERATION IN GENE ACT.Judith Christman; Fiscal Year: 1992..Cloned hepatitis B virus DNA will be used as the substrate for all experiments since the expression of viral genes is affected by methylation and 5azaCR treatment...
- Intestinal Cancer Chemoprevention: Molecular MechanismsWancai Yang; Fiscal Year: 2009..abstract_text> ..
- 5-AZACYTIDINE INDUCED DIFFERENTIATIONPeter Jones; Fiscal Year: 1980..The ability of 5-azacytidine and other analogs of cytidine to inhibit DNA methylation are being determined since we have preliminary evidence suggesting that this inhibition is related to their mechanism of action...
- Control of hTERT in initiation and progression of agingTrygve Tollefsbol; Fiscal Year: 2002..These studies are intended to strengthen the potential for development of therapeutic control of hTERT expression during aging and in age-associated diseases such as cancer. ..
- SUSTAINED GENE EXPRESSION FROM RETROVIRAL VECTORSCHRISTOPHER KLUG; Fiscal Year: 2002..abstract_text> ..
- MOLECULAR STUDIES OF DNA STRUCTURAL LESIONSG Beardsley; Fiscal Year: 1992..Using NMR spectroscopy, we will investigate the physicochemical consequences of these lesions. Through construction of computer graphic models we will investigate the detailed structural consequences of lesions in DNA...
- Neoplasia and Methylated CpG Islands AmplificationJean 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. ..
- Diet and DNA methylation in colon mucosa and adenomasJean Pierre Issa; Fiscal Year: 2007..These studies should provide definitive information on interactions between diet and DNA methylation in human colorectal mucosa and cancer. [unreadable] [unreadable]..
- DNA METHYLATION IN DEVELOPMENT AND CANCERPeter Jones; Fiscal Year: 2000....
- RATIONAL SEQUENCING OF NUCLEOSIDE DRUG ANALOGUESEdwin Cadman; Fiscal Year: 1980..Current work is designed to investigate the intracellular perturbations that result from various pyrimidine inhibitors (PALA, FdUrd) and then exploit these changes in designing sequence studies with nucleoside analogues. ..
- METHYLATION PROFILING IN COLORECTAL CANCERJean 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. ..
- DNA Methylation in Colon Cancer MetastasisJean Pierre Issa; Fiscal Year: 2008..abstract_text> ..
- Phase I study of 5-aza-2?-deoxycitidine in acute lymphocytic leukemiaGuillermo Garcia Manero; Fiscal Year: 2008..In this proposal, we plan to develop a new form of low-dose chemotherapy, decitabine, for these patients. Early results indicate that this is active and safe. [unreadable] [unreadable] [unreadable]..
- Cell Cycle Controlling Genes in Adult Acute LymphomaGuillermo Garcia Manero; Fiscal Year: 2005..abstract_text> ..
- Phase1/11 study of 5-aza-2'-deoxycytidine and valproic *Guillermo Garcia Manero; Fiscal Year: 2005..Decitabine will be generously provided by SuperGen (r). Valproic acid is an FDA approved anti-convulsant. ..
- CANCER AND LEUKEMIA GROUP B--MOUNT SINAILewis Silverman; Fiscal Year: 2002..With these associated investigators in 12 affiliated institutions, Mount Sinai plans to participate in all Group activities. ..
- Mechanism of combined 'epigenetic therapy' in myeloid malignanciesSteven Gore; Fiscal Year: 2009..with myeloid malignancies designed to estimate clinical response rates to a novel schedule of the DNMTi 5- azacitidine (SAC), alone and in combination with the oral HDACi MS-275 to determine whether the addition of the HDACi ..
- DNA METHYLTRANSFERASE/HISTONE DEACETYLASE INHIBITIONSteven Gore; Fiscal Year: 2002..This will enable determination of the "molecular response rate" to this therapy and preliminary exploration of correlation between these molecular endpoints and clinical response. ..
- Arsenic Trioxide in Primary Curative APL TherapySteven Gore; Fiscal Year: 2008..Success of this trial will potentially be followed by the testing of regimen against more conventional and more extensive treatment for APL in a Phase III trial. [unreadable] [unreadable] [unreadable]..
- Phase I/II Study of MS-275 and 5-Azacytidine in Patients with Advanced Non-SmallCHARLES RUDIN; Fiscal Year: 2008..If successful, this approach could alter the poor prognosis of individuals with this disease. [unreadable] [unreadable] [unreadable]..
- Gene Methylation and Therapeutic Response in Lung CancerSteven Belinsky; Fiscal Year: 2005..The validation of these genes as biomarkers of lung cancer risk and their detection in sputum and/or serum could ultimately support chemoprevention trials for preventing lung cancer. ..
- MARKERS FOR LUNG CARCINOGENESIS IN BRONCHIAL EPITHELIUMSteven Belinsky; Fiscal Year: 2001..f., simply markers of exposure) and help identify genetic alterations that are candidate markers of respiratory carcinogenesis. ..
- TUMOR SUPPRESSOR GENE METHYLATION IN LUNG ADENOCARCINOMASteven A Belinsky; Fiscal Year: 2010..Transient transfection of minimized promoters into cell lines with an endogenously active or silenced gene will be used to elucidate the sequence of changes involved in repression of promoter activity. REVISED: July 7, 2005 ..
- Commitment of Stem Cells to the Adipocyte LineageROBERT BOWERS; Fiscal Year: 2007..Further, the ability of the identified genes/proteins to induce adipocyte lineage commitment will be tested with both ex vivo and in vivo models. Targets for obesity therapies may be found. [unreadable] [unreadable]..
- Aberrant gene expression in CD4+CD28-T cells: mechanismsBruce C Richardson; Fiscal Year: 2010..These studies will identify mechanisms modifying gene expression in this pathologic subset, and suggest ways to restore normal gene expression in these cells. ..
- FETAL GLOBIN INDUCTION IN BETA THALASSEMIASusan Perrine; Fiscal Year: 2002..These studies should determine the proportion and some genotypes of beta thalassemia patients which can benefit from Pulsed Butyrate plus/minus rhu-EP0 therapy. ..
- SIGNIFICANCE OF AGE DEPENDENT CHANGES IN DNA METHYLATIONBruce Richardson; Fiscal Year: 2002..This approach may also prove useful in characterizing genes that have altered expression with aging in lymphocytes and other cell types, and that may contribute to the development of autoimmunity and malignancies in the elderly. ..
- Pharmacophore-Modeled Screening for HbF-Inducing AgentsSusan Perrine; Fiscal Year: 2004..virtual screening using molecular modeling with confirmation by reporter assay and selection of a specific HDAC activity should generate additional compounds for development of an optimal HbF inducer for an effective life-long treatment ..
- Environmental effects on lupus T cell DNA methylation and gene expressionBruce Richardson; Fiscal Year: 2009..Evidence that dietary modification can ameliorate aberrant gene expression in vitro and disease severity in the murine model will lead to studies extending these results to lupus patients. ..
- The Role of MicroRNA in HepatocarcinogenesisKalpana Ghoshal; Fiscal Year: 2007..Further, this proposal fits well with the mission/goals set forth by multiple institutes that include NCI, NIDDK and NIAAA n the etiology, prevention and treatment of hepatocellular carcinomas. [unreadable] [unreadable] [unreadable]..
- Erythropoiesis & pulse arginine butyrate in sickle cellSusan Perrine; Fiscal Year: 2005..Abstract Not Provided ..