Affiliation: Johns Hopkins University
- In vitro basis for treatment with hypomethylating agents and histone deacetylase inhibitors: can epigenetic changes be used to monitor treatment?Steven D Gore
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD 21287, USA
Leuk Res 33:S2-6. 2009..Trials are ongoing to investigate early methylation changes and DNA damage markers to understand the mechanisms of these drugs and as potential predictors of clinical response...
- Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemiaSteven D Gore
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, CRB1 288, 1650 Orleans St, Baltimore, MD 21231, USA
J Clin Oncol 28:1047-53. 2010..Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate...
- New ways to use DNA methyltransferase inhibitors for the treatment of myelodysplastic syndromeSteven D Gore
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA
Hematology Am Soc Hematol Educ Program 2011:550-5. 2011..New information on the impact of DNMT inhibitors on the immune system and on stem cells will likely lead to novel uses of these drugs in MDS and other hematologic and nonhematologic malignancies...
- Inhibitors of signaling in myelodysplastic syndromeSteven D Gore
Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Cancer Research Building 288, 1650 Orleans Street, Baltimore, MD 21231 1000, USA
Best Pract Res Clin Haematol 17:613-22. 2004..Future therapies in MDS will attempt to resolve cytopenias, eliminate malignant clones and allow differentiation by attacking specific mechanisms of the disease...
- Epigenetic targets in human neoplasmsTamer E Fandy
Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA
Epigenomics 2:221-32. 2010..Evaluating the combination of different epigenetic modifiers and ensuring their optimization are the next challenges towards the establishment of epigenetic therapy...
- Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasmsSteven D Gore
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21287, USA
Cancer Res 66:6361-9. 2006..The promising percentage of major hematologic responses justifies the testing of such combinations in prospective randomized trials...
- Future directions in myelodysplastic syndrome: newer agents and the role of combination approachesSteven D Gore
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Cancer Control 15:40-9. 2008..Utilizing convergent or complementary molecular mechanisms with in vitro or in vivo evidence of synergy is a fresher and maybe a more efficacious approach to combination therapy...
- Enhancing survival outcomes in the management of patients with higher-risk myelodysplastic syndromesSteven D Gore
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
Cancer Control 16:2-10. 2009..This review examines the classification and diagnosis of higher-risk MDS patients, the management goals for these patients, clinical experience involved with treatments, guidelines, and recommendations for therapeutic options...
- Phase I and pharmacokinetic study of flavopiridol followed by 1-beta-D-arabinofuranosylcytosine and mitoxantrone in relapsed and refractory adult acute leukemiasJudith E Karp
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA
Clin Cancer Res 11:8403-12. 2005..These findings warrant continuing development of flavopiridol at 50 mg/m2/d x 3 days in combination with cytotoxic and biological agents for acute leukemias...
- DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromesElizabeth A Griffiths
Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins Hospital, Baltimore, MD 21231, USA
Semin Hematol 45:23-30. 2008..Combination therapy offers the possibility of hematologic improvement and remission to myelodysplastic patients with previously untreatable disease...
- Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignanciesTamer E Fandy
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
Blood 114:2764-73. 2009..This trial is registered with http://www.clinicaltrials.gov under NCT00101179...
- Impact of prolonged infusions of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemiaSteven D Gore
The Johns Hopkins Oncology Center, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA
Clin Cancer Res 8:963-70. 2002..Two patients on the 21/28 schedule developed hematological improvement. Prolonged infusions of PB are well tolerated making this an attractive platform for the clinical investigation of HDAC inhibition...
- Durable molecular remissions with a single cycle of timed sequential consolidation chemotherapy in acute promyelocytic leukemiaSteven D Gore
The Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
Am J Hematol 79:119-27. 2005..However, the toxicity of the consolidation module and the development of secondary myelodysplasia despite decreased total therapy emphasize the need to further improve and refine curative therapy for APL...
- Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk acute myelogenous leukemiaJudith E Karp
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231 1000, USA
Clin Cancer Res 13:4467-73. 2007..We have now completed a phase II study of sequential flavopiridol, ara-C, and mitoxantrone in 62 adults with poor-risk AML...
- Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk featuresJudith E Karp
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231 1000, USA
Clin Cancer Res 14:3077-82. 2008..Tipifarnib is an oral farnesyltransferase inhibitor with activity in AML. We conducted a phase II trial of maintenance tipifarnib monotherapy for 48 adults with poor-risk AML in first CR...
- Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemiasIvana Gojo
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA
Blood 109:2781-90. 2007..No responses by classical criteria were seen. Our results show that MS-275 effectively inhibits HDAC in vivo in patients with advanced myeloid leukemias and should be further tested, preferably in patients with less-advanced disease...
- Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purging for acute myeloid leukaemia beyond first remission: a 10-year experienceB Douglas Smith
Johns Hopkins Oncology Center, Bunting Blaustein Cancer Research Building, Rm 246, 1650 Orleans Street, Baltimore, MD 21231, USA
Br J Haematol 117:907-13. 2002..4HC-purged autologous BMT produced results similar to allogeneic BMT for AML patients beyond first remission...
- Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemiaJudith E Karp
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231 1000, USA
Leuk Res 34:877-82. 2010..Short OS and DFS correlated with adverse cytogenetics, regardless of age or treatment in CR. The addition of allogeneic BMT in CR translates into long OS and DFS in the majority of eligible patients...
- Extended follow-up of autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide (4-HC) purging for indolent or transformed non-Hodgkin lymphomasYvette L Kasamon
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Biol Blood Marrow Transplant 17:365-73. 2011..Thus, 4-HC-purged ABMT can produce extended remissions in a subgroup of patients with indolent lymphomas...
- Six (or more) drugs in search of a mechanism: DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromesSteven D Gore
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Baltimore, MD 21231, USA
J Natl Compr Canc Netw 4:83-90. 2006..Such information will be critical in the development of more effective congeners and drug combinations in ongoing attempts to improve the outcome of patients with MDS...
- Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposideJudith E Karp
Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD 21231 1000, USA
Blood 113:4841-52. 2009..These clinical studies are registered at www.clinicaltrials.gov as #NCT00112853...
- Arsenic trioxide - An old drug rediscoveredAshkan Emadi
Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231 1000, United States
Blood Rev 24:191-9. 2010..The chemistry, mechanisms of action, and clinical side effects of As(2)O(3) are also discussed...
- Differentiation therapy in poor risk myeloid malignancies: Results of a dose finding study of the combination bryostatin-1 and GM-CSFB Douglas Smith
Johns Hopkins Medical Institute, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA
Leuk Res 35:87-94. 2011..We developed a dose finding trial to assess toxicity, differentiating activity, and clinical impact of the combination of bryostatin-1 and GM-CSF...
- 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. 2005..To characterize the pharmacokinetic behavior of 5-azacitidine (5-AC), a cytidine nucleoside analog, when given with phenylbutyrate, a histone deaceytlase inhibitor...
- A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemiasJudith E Karp
Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231 1000, USA
Blood 110:1762-9. 2007..This clinical trial is registered with the National Cancer Institute's PDQ at www.clinicaltrials.gov as no. JHOC-J0561...
- DNA demethylating agents and histone deacetylase inhibitors in hematologic malignanciesTamer E Fandy
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Cancer J 13:40-8. 2007..This review focuses on the pharmacology of the known DNA methyltransferase and histone deacetylase inhibitors and their potential as promising anticancer drugs...
- Intravenous azacitidine for MDSSteven D Gore
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Clin Adv Hematol Oncol 5:234. 2007
- Novel approaches for myelodysplastic syndromes: beyond hypomethylating agentsArturo Loaiza-Bonilla
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA
Curr Opin Hematol 17:104-9. 2010..Several novel therapeutic approaches exist for treatment of patients with myelodysplastic syndrome, with goals to improve quality of life and prolong survival. This review highlights new therapies from the last 18 months...
- Flavopiridol synergizes TRAIL cytotoxicity by downregulation of FLIPLTamer E Fandy
School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA
Cancer Chemother Pharmacol 60:313-9. 2007..We investigated the effect of flavopiridol pretreatment on TRAIL cytotoxicity and on the expression of FLIP(L) in different TRAIL-resistant cell lines, because FLIP expression is known to confer TRAIL-resistance...
- Combination therapy with DNA methyltransferase inhibitors in hematologic malignanciesSteven D Gore
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Nat Clin Pract Oncol 2:S30-5. 2005....
- DNA methyltransferase inhibitors: class effect or unique agents?Elizabeth A Griffiths
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
Leuk Lymphoma 49:650-1. 2008
- Oral valacyclovir as prophylaxis against herpes simplex virus reactivation during high dose chemotherapy for leukemiaRobert Z Orlowski
The Sidney Kimmel Comprehensive Cancer Center, Divisions of Hematological Malignancies, Baltimore, Maryland 21287 8985, USA
Leuk Lymphoma 45:2215-9. 2004....
- Progressive chromatin repression and promoter methylation of CTNNA1 associated with advanced myeloid malignanciesYing Ye
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cancer Res 69:8482-90. 2009....
- Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter hypermethylationElizabeth A Griffiths
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Leuk Lymphoma 51:1711-9. 2010....
- Emerging drugs for the treatment of myelodysplastic syndromePhilip J Nivatpumin
Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Expert Opin Emerg Drugs 10:569-90. 2005..Our improved understanding of the molecular pathogenesis of MDS has resulted in several new promising therapeutic agents. This review will consider the rational development of new agents based on the molecular biology of MDS...
- State of the translational science: summary of Baltimore workshop on gene re-expression as a therapeutic target in cancer January 2003Arthur Zelent
Section of Hematological Oncology, Institute of Cancer Research, Chester Beatty Laboratories, London, England
Clin Cancer Res 10:4622-9. 2004..Other classes of agents that may be rationally combined with these classes of drugs include retinoids, steroid hormones, and cytotoxic drugs...
- Alkyl-substituted polyaminohydroxamic acids: a novel class of targeted histone deacetylase inhibitorsSheeba Varghese
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan 48202, USA
J Med Chem 48:6350-65. 2005..On the basis of these results, PAHAs 6-21 represent an important new chemical class of HDAC inhibitors...
- Clinical translation of epigenetics in cancer: eN-CORe--a report on the second workshopArthur Zelent
Section of Hemato-Oncology, Institute of Cancer Research, London, United Kingdom
Mol Cancer Ther 4:1810-9. 2005..The aim of this article is to summarize topics discussed at this workshop and highlight conclusions as to the immediate and long-term future of epigenetic therapy in cancer...
- Addition of histone deacetylase inhibitors in combination therapyHetty E Carraway
J Clin Oncol 25:1955-6. 2007
- Commentary: topoisomerases as targets in acute leukemia: I, II, I plus II or none?Sami N Malek
Leuk Res 27:1-3. 2003
- Derepression in the desert: the third workshop on clinical translation of epigenetics in cancer therapeuticsArthur Zelent
Institute of Cancer Research, Sutton, Surrey, United Kingdom
Cancer Res 68:4967-70. 2008
- DecitabineSteven D Gore
Nat Rev Drug Discov 5:891-2. 2006
- Future directions for the use of hypomethylating agentsGuillermo Garcia-Manero
Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
Semin Hematol 42:S50-9. 2005..This review discusses the potential use of methylation reversing agents in the treatment of solid tumors and in benign hematologic disorders along with the rationale for combination therapies using hypomethylating agents...
- Central role of Fas-associated death domain protein in apoptosis induction by the mitogen-activated protein kinase kinase inhibitor CI-1040 (PD184352) in acute lymphocytic leukemia cells in vitroXue Wei Meng
Division of Oncology Research, Guggenheim 1342C, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
J Biol Chem 278:47326-39. 2003..Collectively, these results identify the MAPK pathway as a potential therapeutic target in ALL and delineate a mechanism by which MEK inhibition triggers apoptosis in ALL cells...
- Myelodysplastic syndromes clinical practice guidelines in oncologyPeter L Greenberg
Stanford Hospital and Clinics, Stanford, CA, USA
J Natl Compr Canc Netw 4:58-77. 2006
- Autoimmune phenomena in patients with myelodysplastic syndromes and chronic myelomonocytic leukemiaMuhammad Wasif Saif
Division of Hematology Oncology, Wallace Tumour Institute, University of Alabama, Room 262 A, 1824 6th Avenue South, Birmingham, AL 35294 3300, USA
Leuk Lymphoma 43:2083-92. 2002..We also review the incidence, nature, course and response to therapy of these manifestations and discuss potential pathogenic mechanisms...
- Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasiaBruce D Cheson
Department of Hematology/Oncology, Georgetown University Hospital, Washington, DC, USA
Blood 108:419-25. 2006..Because limitations of the IWG criteria have surfaced, based on practical and reported experience, some modifications were warranted. In this report, we present recommendations for revisions of some of the initial criteria...
- Arsenic Trioxide in Primary Curative APL TherapySteven Gore; Fiscal Year: 2007..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. ..
- 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. ..
- Mechanism of combined 'epigenetic therapy' in myeloid malignanciesSteven Gore; Fiscal Year: 2009....