J E Karp
Affiliation: University of Maryland
- Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trialJ E Karp
University of Maryland Greenebaum Cancer Center, 22 S Greene St, Baltimore, MD 21201, USA
Blood 97:3361-9. 2001..The results of this first clinical trial of a signal transduction inhibitor in patients with acute leukemias suggest that inhibitors of FT may have important clinical antileukemic activity. (Blood. 2001;97:3361-3369)..
- Current status of clinical trials of farnesyltransferase inhibitorsJ E Karp
University of Maryland Greenebaum Cancer Center, Baltimore, Maryland 21201, USA
Curr Opin Oncol 13:470-6. 2001..Preclinical studies of farnesyltransferase inhibitor resistance and clinical trials of farnesyltransferase inhibitors in combination with other agents currently are in progress...
- Induction of acute lymphocytic leukemia differentiation by maintenance therapyT L Lin
The Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Leukemia 21:1915-20. 2007..These data suggest that induction of leukemia progenitor differentiation plays an important role in the mechanism of action of maintenance therapy in ALL...
- Farnesyl protein transferase inhibitors as targeted therapies for hematologic malignanciesJ E Karp
Department of Medicine, Greenebaum Cancer Center, University of Maryland School of Medicine, 22 S. Greene St, Baltimore, MD 21201, USA
Semin Hematol 38:16-23. 2001..The biologic and antitumor activity and favorable tolerability of R115777 support further clinical evaluation alone and in combination therapy in hematologic malignancies...
- New concepts in the treatment of acute myeloid malignancies: selected pathways for targeted therapyB D Smith
Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA
J Biol Regul Homeost Agents 19:23-32. 2005....
- A pharmacodynamic study of sorafenib in patients with relapsed and refractory acute leukemiasK W Pratz
Division of Hematologic Malignancies, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Leukemia 24:1437-44. 2010..Although sorafenib showed only modest clinical activity as a single agent in this heavily treated population, robust inhibition of FLT3 and ERK suggests that there may be a potential important role in combination therapies...
- Expression of breast cancer resistance protein in blast cells from patients with acute leukemiaD D Ross
University of Maryland Greenebaum Cancer Center the Department of Medicine, Division of Hematology Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Blood 96:365-8. 2000..High expression of BCRP mRNA is sufficiently frequent in AML to warrant more extensive investigations to determine the relation of disease subtype and treatment outcome to BCRP expression and function...
- Farnesyltransferase inhibitors (FTIs) in myeloid malignanciesJ E Karp
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Room 289, Baltimore, Maryland, USA
Ann Hematol 83:S87-8. 2004..It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents...
- Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitorsMark Levis
Kimmel Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA
Blood 108:3477-83. 2006..Additionally, our results suggest that nonselectivity may constitute an important component of the cytotoxic effect of FLT3 inhibitors in FLT3-mutant AML...
- 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...
- 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...
- 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....
- Developmental clinical trials: building one step at a timeJudith E Karp
Leuk Res 30:765-6. 2006
- Histone deacetylase inhibitor pharmacodynamic analysis by multiparameter flow cytometryEun Joo Chung
Medical Oncology Clinical Research Unit, Bethesda, MD 20892, USA
Ann Clin Lab Sci 35:397-406. 2005..The technique described has significant advantages for the PD assessment of HDAC inhibitors as monotherapy and as a component of combination therapy trials...
- Factors affecting the pharmacokinetic profile of MS-275, a novel histone deacetylase inhibitor, in patients with cancerMilin R Acharya
Clinical Pharmacology Research Core, National Cancer Institute, Bethesda, MD, USA
Invest New Drugs 24:367-75. 2006..To evaluate elimination pathways of the histone deacetylase inhibitor MS-275 in vitro and screen for relationships between demographic factors that may affect its pharmacokinetics in vivo...
- Phase I and pharmacokinetic study of Triapine, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignanciesIvana Gojo
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA
Leuk Res 31:1165-73. 2007..2-5.5 microM) was above levels required to achieve in vitro/in vivo leukemia growth inhibition. Based on these data, we conclude that Triapine warrants further investigation in hematologic malignancies...
- Ribonucleotide reductase: an old target with new potentialB Douglas Smith
Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD 21210, USA
Leuk Res 27:1075-6. 2003
- Involvement of reactive oxygen species in adaphostin-induced cytotoxicity in human leukemia cellsJoya Chandra
Division of Oncology Research, Guggenheim 1301, Mayo Clinic, 200 First St, SW, Rochester, MN 55901, USA
Blood 102:4512-9. 2003....
- Mcl-1 as a buffer for proapoptotic Bcl-2 family members during TRAIL-induced apoptosis: a mechanistic basis for sorafenib (Bay 43-9006)-induced TRAIL sensitizationXue Wei Meng
Divisions of Oncology Research, Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
J Biol Chem 282:29831-46. 2007..Collectively, these observations not only suggest a model in which Mcl-1 confers TRAIL resistance by serving as a buffer for Bak, Bim, and Puma, but also identify sorafenib as a potential modulator of TRAIL sensitivity...
- Farnesyltransferase inhibitors and myeloid malignancies: phase I evidence of Zarnestra activity in high-risk leukemiasJeffrey E Lancet
University of Rochester, James P Wilmot Cancer Center, Rochester, NY, USA
Semin Hematol 39:31-5. 2002..These results suggest that Zarnestra should be studied further in patients with myeloid leukemia...
- Regulation of leukemic cell adhesion, proliferation, and survival by beta-cateninEun Joo Chung
Medical Oncology Clinical Research Unit and Developmental Therapeutics Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Blood 100:982-90. 2002..Fas-mediated apoptosis was potentiated by inhibition of beta-catenin nuclear signaling. The data suggest that beta-catenin can play a significant role in promoting leukemic cell proliferation, adhesion, and survival...
- The long road to a cure for acute myelocytic leukemia: from intensity to specificityWilliam P Vaughan
University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
J Clin Oncol 26:3475-7. 2008
- 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...
- A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemiaMitch Raponi
Veridex, 3210 Merryfield Row, La Jolla, CA 92121, USA
Blood 111:2589-96. 2008..Therefore, these data indicate that a 2-gene expression assay may have utility in categorizing a population of patients with AML who are more likely to respond to tipifarnib...
- Development of farnesyltransferase inhibitors for clinical cancer therapy: focus on hematologic malignanciesJudith E Karp
Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21231, USA
Cancer Invest 25:484-94. 2007..Clinical trials and correlative laboratory studies in progress and under development will define the optimal roles of FTIs in cancer patients...
- 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...
- A phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloprolJudith E Karp
Leukemia Program, Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231 1000, USA
Leuk Res 32:71-7. 2008..Drug-related toxicities included fever and metabolic acidosis. Triapine 105 mg/m(2) followed by fludarabine 30 mg/m2 daily x 5 is active in refractory myeloid malignancies and warrants continuing study for patients with aggressive MPD...
- 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...
- Exploiting oxidative damage to overcome resistanceJudith E Karp
Leuk Res 30:1213-4. 2006
- Development of the farnesyltransferase inhibitor tipifarnib for therapy of hematologic malignanciesJudith E Karp
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Division of Hematologic Malignancies, The Bunting Blaustein Cancer Research Building, Baltimore, MD 21231, USA
Future Oncol 1:719-31. 2005..The full development of FTIs for the therapy of hematologic malignancies will require the design and testing of rational combinations of cytotoxic, biologic and immunomodulatory agents in the laboratory and the clinic...
- Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trialJudith E Karp
University of Maryland Greenebaum Cancer Center, Baltimore, Maryland 2120, USA
Clin Cancer Res 9:307-15. 2003..trigger apoptosis in fresh acute leukemia; and (b). recruit surviving leukemic cells to a proliferative state, thereby priming such cells for the S-phase-related cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C)...
- SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromesFrancis J Giles
Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX 77030, USA
Blood 102:795-801. 2003..Studies of other RTKI and/or other antiangiogenic approaches, with correlative studies to examine biologic effects, may be warranted in patients with AML/MDS...
- Farnesyl transferase inhibitors in myeloid malignanciesJeffrey E Lancet
University of Rochester, James P Wilmot Cancer Center, 601 Elmwood Avenue, Box 704 Rochester, NY 14642, USA
Blood Rev 17:123-9. 2003....
- Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapyJeffrey E Lancet
James P Wilmot Cancer Center, University of Rochester, 601 Elmwood Ave, Box 704, Rochester, NY 14642, USA
Blood 102:3880-9. 2003..It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents...
- Quantitative analysis of breast cancer resistance protein and cellular resistance to flavopiridol in acute leukemia patientsTakeo Nakanishi
Department of Medicine, Division of Hematology Oncology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
Clin Cancer Res 9:3320-8. 2003..In vitro cell viability and apoptosis were examined after 24 h exposure to flavopiridol...
- 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...
- Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabinofuranosylcytosine, mitoxantrone, and bevacizumabJudith E Karp
University of Maryland Greenebaum Cancer Center, Baltimore, Maryland, USA
Clin Cancer Res 10:3577-85. 2004..We conducted a Phase II clinical trial of bevacizumab administered after chemotherapy to adults with refractory or relapsed AML, using a timed sequential therapy (TST) approach...
- 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...
- Farnesyl transferase inhibitors in myeloid disordersJeffrey E Lancet
H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA
Oncology (Williston Park) 19:1043-9; discussion 1049-50, 1053-4. 2005....
- Phase I and pharmacologic study of infusional topotecan and Carboplatin in relapsed and refractory acute leukemiaScott H Kaufmann
Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55901, USA
Clin Cancer Res 11:6641-9. 2005..To assess the maximum tolerated dose, toxicities, pharmacokinetics, and antileukemic activity of topotecan and carboplatin in adults with recurrent or refractory acute leukemias...
- New agents in the treatment of acute myeloid leukemia: a snapshot of signal transduction modulationTing Bao
Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
Clin Adv Hematol Oncol 3:287-96, 302. 2005..This review will focus on several exciting components of these pathways and the agents targeting these pathways that are entering clinical trials...
- A phase I and pharmacologic study of idarubicin, cytarabine, etoposide, and the multidrug resistance protein (MDR1/Pgp) inhibitor PSC-833 in patients with refractory leukemiaKenneth S Bauer
Greenebaum Cancer Center, University of Maryland School of Pharmacy, Allied Health Building Suite 540, 100 Penn Street, Baltimore, MD 21201, USA
Leuk Res 29:263-71. 2005..This combination including PSC-833 was well tolerated. Although a pharmacokinetic interaction might have been expected, PSC-833 did not significantly alter the disposition of idarubicin...
- Farnesyl transferase inhibition in hematologic malignanciesJudith E Karp
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Harry and Jeanette Weinberg Building, Suite 1100, 401 North Broadway, Baltimore, MD 21231, USA
J Natl Compr Canc Netw 3:S37-40. 2005
- Overcoming drug resistance: targeting more than one siteJudith E Karp
Greenebaum Cancer Center, University of Maryland, Baltimore, MD 21201, USA
Leuk Res 26:107-9. 2002