Experimental Therapeutics of Leukemia

Summary

Principal Investigator: John C Byrd
Abstract: The Ohio State University is requesting support for a Specialized Program of Research Excellence (SPORE) in leukemia. The focus and goal of this application is highly translational research that improves our understanding of leukemia development, risk stratification and therapy. Central to the success of this SPORE is a cadre of senior investigators who have worked together for years to identify new prognostic factors and treatments for different types of leukemia. Realizing the value of this group and the potential for a Leukemia SPORE to further enhance translational research outcome, OSU has committed financial resources of over $1.4 million per year to support this effort. This SPORE will work to develop novel prognostic factors and therapies to benefit leukemia patients, and additionally will actively engage women and minorities in this endeavor both at the investigator and patient levels. The Projects in this SPORE are: Project 1 - Drs. de la Chapelle &Byrd: Early Predisposing Genes and Risk Stratification for CLL. This project will examine biology of DAPK1 and the prognostic significance of early events in risk stratification of CLL. Project 2 - Drs. Bloomfield &Marcucci: Molecular Characterization and Risk Stratification of Acute Myeloid Leukemia (AML). This project will study the impact of select prognostic gene (FLT3 ITD, MLL PTD, NPM1, WT-1, CEBPA, KIT) mutations, aberrant gene (BAALC, ERG, FLT3, MN1 and EVI1) expression, and mRNA/miRNA expression profiles, on predicting treatment outcome of newly diagnosed AML patients. Project 3 - Drs. Byrd &Lin: Lenalidomide as an Immune Modulating Agent for Chronic Lymphocytic Leukemia (CLL). This work will focus on the mechanism of lenalidomide-induced CLL cell activation and its contribution both to efficacy and to tumor flare, and will examine strategies to reduce morbidity and improve efficacy. Project 4 - Drs. Caligiuri, Marcucci, &Blum: Pre-Clinical and Clinical Investigation of MLL-PTD AML. This project will focus on utilizing a novel MLL PTD mouse model to characterize events in leukemic transformation and to pre-clinically study novel therapeutic approaches for this subset of patients. This project will also initiate a clinical trial of epigenetic therapy to improve the outcome of patients with MLL PTD[+] AML. Project 5 - Drs. Grever &Lee: Pre-clinical and Clinical Development of Silvestrol in CLL. This project will investigate how the novel agent silvestrol mediates B-cell specific cytotoxicity via translational inhibition of apoptotic proteins crucial to B-cell survival, and will facilitate Phase I development of this agent through the NCI. Five Cores accompany these Projects: (A-SPORE Leukemia Tissue Bank;B-Biostatistics;C-Biomedical Informatics;D-Medicinal Chemistry and;E-Administration and Operations). In addition, we have developed a robust developmental research program and career development program to augment the efforts of this SPORE. We believe that this SPORE group, as a multidisciplinary, highly interactive and accomplished team, will have a substantial impact on improving the clinical outcome of leukemia patients.
Funding Period: 2009-08-17 - 2014-07-31
more information: NIH RePORT

Top Publications

  1. pmc Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia
    William 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
  2. pmc Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties
    Sarwish Rafiq
    Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, OH 43210, USA
    J Immunol 190:2702-11. 2013
  3. pmc Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: a novel epigenetic-targeting approach in acute myeloid leukemia
    A Mims
    Department of Internal Medicine, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
    Leukemia 27:871-8. 2013
  4. pmc In vivo quantification of active decitabine-triphosphate metabolite: a novel pharmacoanalytical endpoint for optimization of hypomethylating therapy in acute myeloid leukemia
    Hongyan Wang
    Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
    AAPS J 15:242-9. 2013
  5. pmc Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: results of sequential cancer and leukemia group B studies
    Jennifer A Woyach
    Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 31:440-7. 2013
  6. pmc Identification of endoplasmic reticulum stress-inducing agents by antagonizing autophagy: a new potential strategy for identification of anti-cancer therapeutics in B-cell malignancies
    Emilia Mahoney
    Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA
    Leuk Lymphoma 54:2685-92. 2013
  7. pmc Emerging drug profile: cyclin-dependent kinase inhibitors
    James S Blachly
    Division of Hematology
    Leuk Lymphoma 54:2133-43. 2013
  8. pmc Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia
    Houda Alachkar
    Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA
    J Hematol Oncol 6:21. 2013
  9. pmc Patients with chronic lymphocytic leukemia with high-risk genomic features have inferior outcome on successive Cancer and Leukemia Group B trials with alemtuzumab consolidation: subgroup analysis from CALGB 19901 and CALGB 10101
    Jeffrey A Jones
    Division of Hematology, The Ohio State University, Columbus, OH, USA
    Leuk Lymphoma 54:2654-9. 2013
  10. ncbi Improving the treatment outcome of patients with chronic lymphocytic leukemia through targeted antibody therapy
    Deborah M Stephens
    Division of Hematology, Department of Internal Medicine, The Arthur G James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    Hematol Oncol Clin North Am 27:303-27. 2013

Research Grants

  1. Chicago Prevention and Intervention Epicenter (Chicago PIE)
    ROBERT ALAN WEINSTEIN; Fiscal Year: 2013
  2. SPORE in Soft Tissue Sarcoma
    Samuel Singer; Fiscal Year: 2013

Detail Information

Publications124 found, 100 shown here

  1. pmc Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia
    William 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...
  2. pmc Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties
    Sarwish Rafiq
    Integrated Biomedical Science Graduate Program, The Ohio State University, Columbus, OH 43210, USA
    J Immunol 190:2702-11. 2013
    ..These findings bear relevance to potential combination strategies with each of these anti-CD20 Abs in the treatment of CLL...
  3. pmc Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: a novel epigenetic-targeting approach in acute myeloid leukemia
    A Mims
    Department of Internal Medicine, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
    Leukemia 27:871-8. 2013
    ....
  4. pmc In vivo quantification of active decitabine-triphosphate metabolite: a novel pharmacoanalytical endpoint for optimization of hypomethylating therapy in acute myeloid leukemia
    Hongyan Wang
    Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
    AAPS J 15:242-9. 2013
    ..Higher levels are seemingly associated with clinical response. Monitoring the DAC-TP intracellular level may serve as a novel pharmacological endpoint for designing more effective DAC-based regimens...
  5. pmc Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: results of sequential cancer and leukemia group B studies
    Jennifer A Woyach
    Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 31:440-7. 2013
    ..Chronic lymphocytic leukemia (CLL) is a disease of the elderly, yet few clinical trials include a significant number of older patients, and outcomes after specific therapies can be different depending on age...
  6. pmc Identification of endoplasmic reticulum stress-inducing agents by antagonizing autophagy: a new potential strategy for identification of anti-cancer therapeutics in B-cell malignancies
    Emilia Mahoney
    Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA
    Leuk Lymphoma 54:2685-92. 2013
    ..These results identify a novel strategy potentially effective in CLL treatment, by repositioning two well-known drugs as a combinatorial therapy with anti-cancer properties...
  7. pmc Emerging drug profile: cyclin-dependent kinase inhibitors
    James S Blachly
    Division of Hematology
    Leuk Lymphoma 54:2133-43. 2013
    ..In additional to flavopiridol and dinaciclib, we also review the current status of other members of this class, and provide commentary as to the future direction of combination therapy including CDK inhibitors. ..
  8. pmc Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia
    Houda Alachkar
    Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA
    J Hematol Oncol 6:21. 2013
    ..We examined here the preclinical activity of silvestrol in FLT3-ITD and FLT3 wild-type (wt) AML...
  9. pmc Patients with chronic lymphocytic leukemia with high-risk genomic features have inferior outcome on successive Cancer and Leukemia Group B trials with alemtuzumab consolidation: subgroup analysis from CALGB 19901 and CALGB 10101
    Jeffrey A Jones
    Division of Hematology, The Ohio State University, Columbus, OH, USA
    Leuk Lymphoma 54:2654-9. 2013
    ..004). Results were similar when restricting to patients who received at least one dose of alemtuzumab consolidation, demonstrating limited ability to overcome the poor outcome associated with high-risk genetic features...
  10. ncbi Improving the treatment outcome of patients with chronic lymphocytic leukemia through targeted antibody therapy
    Deborah M Stephens
    Division of Hematology, Department of Internal Medicine, The Arthur G James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    Hematol Oncol Clin North Am 27:303-27. 2013
    ..This review discusses the currently approved and novel mAbs for the treatment of CLL...
  11. pmc Protein phosphatase 2A: a target for anticancer therapy
    Danilo Perrotti
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210 2207, USA
    Lancet Oncol 14:e229-38. 2013
    ..Here, we discuss PP2A as a druggable tumour suppressor in view of the possible introduction of PP2A-activating drugs into anticancer therapeutic protocols...
  12. pmc Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients
    Guido Marcucci
    The Ohio State University, Comprehensive Cancer Center, Biomedical Research Tower 460 W 12th Ave, Columbus, OH 43210, USA
    J Clin Oncol 31:2086-93. 2013
    ....
  13. pmc Targeted delivery of microRNA-29b by transferrin-conjugated anionic lipopolyplex nanoparticles: a novel therapeutic strategy in acute myeloid leukemia
    Xiaomeng Huang
    Molecular, Cellular and Developmental Biology, The Ohio State University, Columbus, Ohio 43210, USA
    Clin Cancer Res 19:2355-67. 2013
    ..To overcome these limitations, we developed a novel transferrin-conjugated nanoparticle delivery system for synthetic miR-29b (Tf-NP-miR-29b)...
  14. pmc Identification of a 24-gene prognostic signature that improves the European LeukemiaNet risk classification of acute myeloid leukemia: an international collaborative study
    Zejuan Li
    University of Chicago, Chicago, IL 60637, USA
    J Clin Oncol 31:1172-81. 2013
    ..To identify a robust prognostic gene expression signature as an independent predictor of survival of patients with acute myeloid leukemia (AML) and use it to improve established risk classification...
  15. pmc Germline allele-specific expression of DAPK1 in chronic lymphocytic leukemia
    Quan Xiang Wei
    Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany
    PLoS ONE 8:e55261. 2013
    ..Our data indicate that ASE at the DAPK1 gene locus is a recurrent event, mediated by epigenetic mechanisms and potentially predisposing to CLL...
  16. pmc Milatuzumab-conjugated liposomes as targeted dexamethasone carriers for therapeutic delivery in CD74+ B-cell malignancies
    Yicheng Mao
    Division of Hematology, The Comprehensive Cancer Center, Division of Pharmaceutics and Medicinal Chemistry, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA
    Clin Cancer Res 19:347-56. 2013
    ..Herein, we developed novel milatuzumab-conjugated liposomes as a targeted dexamethasone carrier for therapeutic delivery in CD74(+) B-cell malignancies and explored its effect against the disease...
  17. pmc ER stress and autophagy: new discoveries in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol
    Emilia Mahoney
    Division of Hematology, Department of Internal Medicine, College of Pharmacy, The Ohio State University OSU, Columbus, OH 43210, USA
    Blood 120:1262-73. 2012
    ....
  18. pmc Molecular prognostic factors in cytogenetically normal acute myeloid leukemia
    Alison Walker
    Comprehensive Cancer Center, Ohio State University, B324 Starling Loving Hall, 320 W 10th Avenue, Columbus, OH 43210, USA
    Expert Rev Hematol 5:547-58. 2012
    ..As the number of mutations continues to expand, bioinformatic algorithms that allow for integration of multiple markers will be necessary to provide optimal care for patients with this disease...
  19. pmc Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation
    Anjali Mishra
    Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
    Cancer Cell 22:645-55. 2012
    ..Drug targeting that reverses miR-29b repression cures otherwise fatal LGL leukemia. We show how excessive IL-15 initiates cancer and demonstrate effective drug targeting for potential therapy of human LGL leukemia...
  20. pmc Variations of the ataxia telangiectasia mutated gene in patients with chronic lymphocytic leukemia lack substantial impact on progression-free survival and overall survival: a Cancer and Leukemia Group B study
    Gerard Lozanski
    Department of Pathology, The Ohio State University, Columbus, OH 43210, USA
    Leuk Lymphoma 53:1743-8. 2012
    ..70), PFS (p =0.59) or OS (p =0.13) were observed. Our data indicate that truncating ATM mutations are rare in patients with CLL. Furthermore, in this dataset, these non-silent variants had limited impact on PFS and OS...
  21. pmc Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia
    Rosa Lapalombella
    Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
    Blood 120:4621-34. 2012
    ..Together, these findings demonstrate that XPO1 is a valid target in CLL with minimal effects on normal cells and provide a basis for the development of SINEs in CLL and related hematologic malignancies...
  22. pmc Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia
    Krzysztof Mrozek
    The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210 1228, USA
    J Clin Oncol 30:4515-23. 2012
    ..To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML)...
  23. pmc Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia
    Bo Yu
    Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA
    Blood 121:136-47. 2013
    ..The broader implications of similar approaches in overcoming immunostimulatory properties of RNA-directed therapeutics in hematologic malignancies are also discussed...
  24. pmc inv(16)/t(16;16) acute myeloid leukemia with non-type A CBFB-MYH11 fusions associate with distinct clinical and genetic features and lack KIT mutations
    Sebastian Schwind
    The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
    Blood 121:385-91. 2013
    ..We conclude that non-type A fusions associate with distinct clinical and genetic features, including lack of KIT mutations, and a unique gene-expression profile...
  25. pmc Zinc-dependent regulation of the Adh1 antisense transcript in fission yeast
    Kate M Ehrensberger
    Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 288:759-69. 2013
    ..Our studies reveal how multiple mechanisms can synergistically control the ratio of sense to antisense transcripts and highlight a novel mechanism by which adh1 gene expression can be controlled by cellular zinc availability...
  26. pmc New recurrent balanced translocations in acute myeloid leukemia and myelodysplastic syndromes: cancer and leukemia group B 8461
    Alison Walker
    Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
    Genes Chromosomes Cancer 52:385-401. 2013
    ....
  27. pmc Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis
    Sahar A Saddoughi
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
    EMBO Mol Med 5:105-21. 2013
    ..Thus, these data suggest that targeting I2PP2A/SET by FTY720 suppresses lung tumour growth, at least in part, via PP2A activation and necroptosis mediated by the kinase domain of RIPK1...
  28. pmc Antibody-based therapeutics for the treatment of human B cell malignancies
    Sivasubramanian Baskar
    Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Curr Allergy Asthma Rep 13:33-43. 2013
    ..This review describes recent advancements in some of these adoptive immunotherapeutic strategies targeting B cell malignancies...
  29. pmc Inhibition of the receptor tyrosine kinase Axl impedes activation of the FLT3 internal tandem duplication in human acute myeloid leukemia: implications for Axl as a potential therapeutic target
    Il Kyoo Park
    Department of Microbiology, Virology, Immunology, and Medical Genetics, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA
    Blood 121:2064-73. 2013
    ..This also suggests that Axl should be pursued as a potential target for the treatment of FLT3-ITD(+) AML...
  30. pmc The proteasome inhibitor carfilzomib functions independently of p53 to induce cytotoxicity and an atypical NF-κB response in chronic lymphocytic leukemia cells
    Sneha V Gupta
    College of Pharmacy, The Ohio State University, Columbus, Ohio, USA
    Clin Cancer Res 19:2406-19. 2013
    ..CLL remains an incurable disease, and new treatments are especially needed in the relapsed/refractory setting. We therefore investigated the effects of the proteasome inhibitor carfilzomib (CFZ) in CLL cells...
  31. pmc A stem cell-like gene expression signature associates with inferior outcomes and a distinct microRNA expression profile in adults with primary cytogenetically normal acute myeloid leukemia
    K H Metzeler
    The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
    Leukemia 27:2023-31. 2013
    ..Fifteen miRs were upregulated in both younger and older CE(high) patients, including miRs relevant for stem cell function. Our results support the clinical relevance of LSCs and improve risk stratification in AML. ..
  32. pmc Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species
    Li Pan
    Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States
    Nat Prod Rep 31:924-39. 2014
    ....
  33. pmc Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia
    John C Byrd
    The authors affiliations are listed in the Appendix
    N Engl J Med 371:213-23. 2014
    ..We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome...
  34. pmc Ocaratuzumab, an Fc-engineered antibody demonstrates enhanced antibody-dependent cell-mediated cytotoxicity in chronic lymphocytic leukemia
    Carolyn M Cheney
    Division of Hematology Department of Internal Medicine The Ohio State University Columbus, OH USA
    MAbs 6:749-55. 2014
    ..If supported by clinical investigation, this feature could potentially allow for subcutaneous dosing at low doses that could expand the potential of administering chemoimmunotherapy in developing countries. ..
  35. pmc How will B-cell-receptor-targeted therapies change future CLL therapy?
    Jeffrey A Jones
    Division of Medicinal Chemistry, College of Pharmacy, and
    Blood 123:1455-60. 2014
    ..This perspective provides a view of where these agents may take us in the future as CLL therapy evolves with this exciting new class of drugs. ..
  36. pmc A novel liposomal formulation of FTY720 (fingolimod) for promising enhanced targeted delivery
    Yicheng Mao
    Center for Affordable Nanoengineering of Polymeric Biomedical Devices CANPBD, The Ohio State University, Columbus, OH, USA Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA
    Nanomedicine 10:393-400. 2014
    ....
  37. pmc Sensitive liquid chromatography/mass spectrometry methods for quantification of pomalidomide in mouse plasma and brain tissue
    Yao Jiang
    Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, United States
    J Pharm Biomed Anal 88:262-8. 2014
    ..5mg/kg. This assay can be applied for thorough characterization of pomalidomide pharmacokinetics and tissue distribution in mice. ..
  38. pmc Bruton's tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL)
    Jennifer A Woyach
    Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH
    Blood 123:1207-13. 2014
    ..Collectively, our data confirm the importance of kinase-functional BTK in CLL. ..
  39. pmc Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification
    Meir Wetzler
    Haematologica 99:308-13. 2014
    ....
  40. pmc Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial
    Susan O'Brien
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Electronic address
    Lancet Oncol 15:48-58. 2014
    ..We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia...
  41. pmc Epigenetics meets genetics in acute myeloid leukemia: clinical impact of a novel seven-gene score
    Guido Marcucci
    Guido Marcucci, Pearlly Yan, Kati Maharry, David Frankhouser, Deedra Nicolet, Klaus H Metzeler, Jessica Kohlschmidt, Krzysztof Mrózek, Yue Zhong Wu, Donna Bucci, John P Curfman, Susan P Whitman, Ann Kathrin Eisfeld, Jason H Mendler, Sebastian Schwind, Heiko Becker, John C Byrd, Ramiro Garzon, Michael A Caligiuri, Stefano Volinia, and Clara D Bloomfield, The Ohio State University Comprehensive Cancer Center Ralf Bundschuh, The Ohio State University, Columbus, OH Kati Maharry, Deedra Nicolet, and Jessica Kohlschmidt, Alliance for Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester, MN Andrew J Carroll, University of Alabama at Birmingham, Birmingham, AL Maria R Baer, Czech Republic
    J Clin Oncol 32:548-56. 2014
    ..However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML...
  42. pmc Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib
    Jennifer A Woyach
    From the Division of Hematology, Department of Internal Medicine J A W, T M L, A S R, S M J, K A B, A L, A J J, J C Byrd, the Department of Biomedical Informatics H G O, A S Y, and the Department of Pathology G L, Ohio State University, Columbus the Department of Medicine, Division of Hematology Oncology, Weill Cornell Medical College, New York R R F the Division of Molecular Genetics, German Cancer Research Center, Heidelberg M Z, P L, and the Department of Internal Medicine III, University of Ulm, Ulm S S both in Germany Pharmacyclics, Sunnyvale, CA L X, D H H L, S M S, D F j, J J B, B Y C the Duke Cancer Institute, Duke University, Durham, NC S S D, J Z the Division of Hematology Oncology, Department of Medicine, Faculty of Science and Technology
    N Engl J Med 370:2286-94. 2014
    ..We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance...
  43. pmc Intronic miR-3151 within BAALC drives leukemogenesis by deregulating the TP53 pathway
    Ann Kathrin Eisfeld
    The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
    Sci Signal 7:ra36. 2014
    ..Thus, this oncogenic miR-3151 may also have a role in solid tumors. ..
  44. pmc Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia
    John C Byrd
    Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, OH 43210, USA
    N Engl J Med 369:32-42. 2013
    ..Bruton's tyrosine kinase (BTK), an essential component of B-cell-receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells...
  45. pmc Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes
    Jason A Dubovsky
    Department of Internal Medicine, Division of Hematology
    Blood 122:2539-49. 2013
    ..This trial was registered at www.clinicaltrials.gov as #NCT01105247 and #NCT01217749. ..
  46. pmc Targeted drug delivery and cross-linking induced apoptosis with anti-CD37 based dual-ligand immunoliposomes in B chronic lymphocytic leukemia cells
    Bo Yu
    Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA
    Biomaterials 34:6185-93. 2013
    ..Our findings suggest that the dual-ligand ILs may provide a preferred strategy of personalized nanomedicine for the treatment of B-cell malignancies...
  47. pmc Cyclophosphamide, alvocidib (flavopiridol), and rituximab, a novel feasible chemoimmunotherapy regimen for patients with high-risk chronic lymphocytic leukemia
    Deborah M Stephens
    Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, United States
    Leuk Res 37:1195-9. 2013
    ..CAR was tolerable and active in high-risk CLL patients without TLS toxicity. With continued monitoring of toxicities, a phase Ib/II study of this combination as frontline therapy is warranted. ..
  48. pmc Glycovariant anti-CD37 monospecific protein therapeutic exhibits enhanced effector cell-mediated cytotoxicity against chronic and acute B cell malignancies
    Sarwish Rafiq
    Integrated Biomedical Science Graduate Program The Ohio State University Columbus, OH USA Division of Hematology, Department of Internal Medicine The Ohio State University Columbus, OH USA
    MAbs 5:723-35. 2013
    ..Collectively, these data suggest potential use of the novel therapeutic agent SMIP-016(GV) with enhanced effector function for B cell malignancies, including CLL and ALL therapy. ..
  49. pmc Characterization of a new chronic lymphocytic leukemia cell line for mechanistic in vitro and in vivo studies relevant to disease
    Erin Hertlein
    Department of Internal Medicine, Division of Hematology, Comprehensive Cancer Center at The Ohio State University, Columbus, Ohio, United States of America
    PLoS ONE 8:e76607. 2013
    ..These studies describe a new CLL cell line that extends currently available models to study gene function in this disease. ..
  50. pmc Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia
    Liat Goldberg
    Cancer Research Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
    Blood 122:2694-703. 2013
    ..Pim1 and the RAS pathway are potential therapeutic targets of these high-risk leukemias. ..
  51. pmc Eradicating acute myeloid leukemia in a Mll(PTD/wt):Flt3(ITD/wt) murine model: a path to novel therapeutic approaches for human disease
    Kelsie M Bernot
    The Ohio State University Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH
    Blood 122:3778-83. 2013
    ..Taken together, these data support that liposomal bortezomib, as a single agent, eradicates Mll(PTD/wt):Flt3(ITD/wt) AML in mouse and may represent a powerful and potentially curative approach to high-risk human disease. ..
  52. pmc PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells
    Paolo Neviani
    J Clin Invest 123:4144-57. 2013
    ..Targeting the JAK2/PP2A/β-catenin network in quiescent HSCs with PADs (e.g., FTY720) has the potential to treat TKI-refractory CML and relieve lifelong patient dependence on TKIs...
  53. pmc Lymphocyte cytosolic protein 1 is a chronic lymphocytic leukemia membrane-associated antigen critical to niche homing
    Jason A Dubovsky
    Division of Hematology, Department of Internal Medicine
    Blood 122:3308-16. 2013
    ..In addition, we identify LCP1 as a membrane-associated target in CLL with confirmed pathogenic significance. This clinical trial was registered at clinicaltrials.gov; study ID number: OSU-0025 OSU-0156. ..
  54. pmc GAS6 expression identifies high-risk adult AML patients: potential implications for therapy
    S P Whitman
    The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
    Leukemia 28:1252-8. 2014
    ....
  55. pmc Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy
    Jennifer A Woyach
    Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, and
    Blood 123:1810-7. 2014
    ..Thus, prolonged lymphocytosis is common following ibrutinib treatment, likely represents the persistence of a quiescent clone, and does not predict a subgroup of patients likely to relapse early. ..
  56. pmc The CD37-targeted antibody-drug conjugate IMGN529 is highly active against human CLL and in a novel CD37 transgenic murine leukemia model
    K A Beckwith
    1 Medical Scientist Training Program, The Ohio State University, Columbus, OH, USA 2 Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
    Leukemia 28:1501-10. 2014
    ..Our results demonstrate the utility of a novel mouse model for evaluating anti-human CD37 therapeutics and highlight the potential of IMGN529 for treatment of CLL and other CD37-positive B-cell malignancies. ..
  57. pmc Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells
    Erin Hertlein
    Department of Internal Medicine, Division of Hematology, The Comprehensive Cancer Center at The Ohio State University, Columbus, OH 43210, USA
    Blood 116:2554-8. 2010
    ..Based on these data, future development of the milatuzumab-immunoliposome formulation as a therapeutic agent for CLL is warranted...
  58. pmc CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain-engineered monoclonal antibody
    Farrukh T Awan
    Division of Hematology Oncology, Department of Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA
    Blood 115:1204-13. 2010
    ..These findings provide strong support for further clinical development of XmAb5574 as both a monotherapy and in combination with lenalidomide for the therapy of CLL and related CD19(+) B-cell malignancies...
  59. pmc Prognostic significance of expression of a single microRNA, miR-181a, in cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
    Sebastian Schwind
    The Ohio State University, Comprehensive Cancer Center, Biomedical Research Tower, 460 W 12th Ave, Columbus, OH 43210, USA
    J Clin Oncol 28:5257-64. 2010
    ....
  60. pmc The clinical application of monoclonal antibodies in chronic lymphocytic leukemia
    Samantha M Jaglowski
    Division of Hematology Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA
    Blood 116:3705-14. 2010
    ..In addition, recent efforts to combine currently applied therapeutic antibodies with other biologic and targeted therapies with efficacy in CLL offers the potential to move toward alternative non-chemotherapy-based treatment approaches...
  61. pmc How much? How frequent? How long? A clinical guide to new therapies in myelodysplastic syndromes
    William Blum
    Division of Hematology, Department of Medicine, The Ohio State University and Comprehensive Cancer Center, Columbus, OH 43210, USA
    Hematology Am Soc Hematol Educ Program 2010:314-21. 2010
    ....
  62. pmc Phase I trial of lenalidomide and CCI-779 in patients with relapsed multiple myeloma: evidence for lenalidomide-CCI-779 interaction via P-glycoprotein
    Craig C Hofmeister
    The Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 29:3427-34. 2011
    ..The preclinical combination of lenalidomide with the mTOR inhibitor CCI-779 has displayed synergy in vitro and represents a novel combination in MM...
  63. pmc Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the pathogenesis of mouse and human CLL
    Shih Shih Chen
    Department of Molecular Virology, Immunology, and Medical Genetics, Human Cancer Genetics Program, The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
    Blood 117:862-71. 2011
    ..Collectively, this study confirms the importance of the silencing of ID4 in murine and human CLL pathogenesis...
  64. pmc High expression of IGFBP2 is associated with chemoresistance in adult acute myeloid leukemia
    Andrea Kühnl
    Department of Hematology and Oncology, Charite University Hospital, Campus Benjamin Franklin, Berlin, Germany
    Leuk Res 35:1585-90. 2011
    ..Thus, our data suggest a role of IGFBP2 and IGF signaling in chemoresistance of AML. Patients with high IGFBP2 expression might benefit from molecular therapies targeting the IGF pathway...
  65. pmc Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712
    Jennifer A Woyach
    The Ohio State University, 320 West 10 Ave, Columbus, OH 43210, USA
    J Clin Oncol 29:1349-55. 2011
    ..The long-term follow-up of these regimens with respect to progression, survival, risk of secondary leukemia, and impact of genomic risk factors has been limited...
  66. pmc ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category
    Klaus H Metzeler
    Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, USA
    Blood 118:6920-9. 2011
    ..This first study of ASXL1 mutations in primary CN-AML demonstrates that ASXL1-mutated older patients, particularly within the ELN Favorable group, have unfavorable outcomes and may be candidates for experimental treatment approaches...
  67. pmc Antitumor effects of OSU-2S, a nonimmunosuppressive analogue of FTY720, in hepatocellular carcinoma
    Hany A Omar
    Division of Medicinal Chemistry, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA
    Hepatology 53:1943-58. 2011
    ..Finally, OSU-2S exhibited high in vivo potency in suppressing xenograft tumor growth in both ectopic and orthotopic models without overt toxicity...
  68. pmc Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765
    Sarah E M Herman
    Integrated Biomedical Science Graduate Program, The Ohio State University Medical Center, Columbus, OH, USA
    Blood 117:6287-96. 2011
    ..Based on these collective data, future efforts targeting BTK with the irreversible inhibitor PCI-32765 in clinical trials of CLL patients is warranted...
  69. pmc Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia
    Sebastian Schwind
    Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
    Blood 118:4188-98. 2011
    ..We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets...
  70. pmc The prognostic and functional role of microRNAs in acute myeloid leukemia
    Guido Marcucci
    Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA
    Blood 117:1121-9. 2011
    ..We review herein results of current studies analyzing changes of microRNA expression in AML and discuss their potential biologic, diagnostic, and prognostic relevance...
  71. pmc Targeting human clonogenic acute myelogenous leukemia cells via folate conjugated liposomes combined with receptor modulation by all-trans retinoic acid
    Hong Li
    Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
    Int J Pharm 402:57-63. 2010
    ..The results demonstrate that the efficiency of FR-mediated targeting of FT-L-DOX was preferentially enhanced by ATRA induced FR-β upregulation in AML clonogenic cells...
  72. pmc Dose escalation of lenalidomide in relapsed or refractory acute leukemias
    William Blum
    Division of Hematology, The Ohio State University and The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
    J Clin Oncol 28:4919-25. 2010
    ..Lenalidomide is effective in myeloma and low-risk myelodysplastic syndromes with deletion 5q. We report results of a phase I dose-escalation trial of lenalidomide in relapsed or refractory acute leukemia...
  73. pmc Lenalidomide treatment promotes CD154 expression on CLL cells and enhances production of antibodies by normal B cells through a PI3-kinase-dependent pathway
    Rosa Lapalombella
    Division of Hematology and Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA
    Blood 115:2619-29. 2010
    ..This study is registered at http://clinicaltrials.gov as NCT00466895...
  74. pmc Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemia
    Shujun Liu
    Division of Hematology Oncology, The Ohio State University, Columbus, OH 43210, USA
    Cancer Cell 17:333-47. 2010
    ....
  75. pmc 17-DMAG targets the nuclear factor-kappaB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition
    Erin Hertlein
    Department of Internal Medicine, Division of Hematology and Oncology, Comprehensive Cancer Center at The Ohio State University, 410West 12th Avenue, Columbus, OH 43210, USA
    Blood 116:45-53. 2010
    ..Therefore, the effect of 17-DMAG on NF-kappaB signaling pathways represents a novel therapy warranting further clinical pursuit in this and other B-cell lymphoproliferative disorders...
  76. pmc Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition
    Wenjun Ni
    Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, United States of America
    PLoS ONE 5:e13792. 2010
    ..This study aimed to evaluate pharmacogenetic factors associated with inter-individual variability in pharmacokinetics and outcomes associated with flavopiridol therapy...
  77. pmc BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
    Sebastian Schwind
    Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
    Blood 116:5660-9. 2010
    ....
  78. pmc FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
    Susan P Whitman
    The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
    Blood 116:3622-6. 2010
    ..FLT3-ITD identifies older CN-AML patients with molecular high risk and is associated with gene- and microRNA-expression signatures that provide biologic insights for novel therapeutic approaches...
  79. pmc Thalidomide and lenalidomide as new therapeutics for the treatment of chronic lymphocytic leukemia
    Farrukh T Awan
    Division of Hematology Oncology, Department of Medicine, Medical College of Georgia, Augusta, GA, USA
    Leuk Lymphoma 51:27-38. 2010
    ..This review examines the existing literature on the use of IMiDs in patients with CLL and provides suggestions for future research in this area...
  80. pmc Evidence-based mini-review: Should patients over the age of 60 with INT-2 or high-risk myelodysplastic syndrome undergo allogeneic stem cell transplantation prior to progression to acute myelogenous leukemia?
    Mark A Schroeder
    Washington University Medical School, St Louis, MO 63110, USA
    Hematology Am Soc Hematol Educ Program 2010:322-4. 2010
    ..He was started on hypomethylating agent treatment and referred for consultation regarding the role of hematopoietic stem cell transplantation. HLA typing results demonstrated that he had an HLA-identical sibling...
  81. pmc Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
    Heiko Becker
    Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
    Blood 116:788-92. 2010
    ..Our results indicate that WT1mut CN-AML represents a distinct entity with poor treatment response across age groups. This study has been registered at www.clinicaltrials.gov as #NCT00900224...
  82. pmc Potential of plant-derived natural products in the treatment of leukemia and lymphoma
    David M Lucas
    Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 410 W 12th Avenue, Columbus, OH 43210, USA
    Curr Drug Targets 11:812-22. 2010
    ....
  83. pmc IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
    Guido Marcucci
    Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 28:2348-55. 2010
    ....
  84. pmc The novel deacetylase inhibitor AR-42 demonstrates pre-clinical activity in B-cell malignancies in vitro and in vivo
    David M Lucas
    Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA
    PLoS ONE 5:e10941. 2010
    ..We therefore investigated the novel DAC inhibitor AR-42 to determine its efficacy in B-cell malignancies...
  85. pmc Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals
    Sarah E M Herman
    Integrated Biomedical Science Graduate Program, TheOhio State University, Columbus, OH, USA
    Blood 116:2078-88. 2010
    ..Collectively, these studies provide rationale for the clinical development of CAL-101 as a first-in-class targeted therapy for CLL and related B-cell lymphoproliferative disorders...
  86. pmc Phase I clinical and pharmacokinetic study of a novel schedule of flavopiridol in relapsed or refractory acute leukemias
    William Blum
    Division of Hematology and Oncology and the Comprehensive Cancer Center, Department of Medicine, The Ohio State University, B310 Starling Loving Hall, 320 West 10 Avenue, Columbus, OH 43210, USA
    Haematologica 95:1098-105. 2010
    ....
  87. pmc CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability
    Brian J Lannutti
    Calistoga Pharmaceuticals Inc, Seattle, WA, USA
    Blood 117:591-4. 2011
    ..These effects have been observed across a broad range of immature and mature B-cell malignancies, thereby providing a rationale for the ongoing clinical evaluation of CAL-101...
  88. pmc Clinical outcome and gene- and microRNA-expression profiling according to the Wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study
    Heiko Becker
    Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
    Haematologica 96:1488-95. 2011
    ..To validate this finding, we investigated pretreatment features and outcome associated with rs16754 in a large cohort of patients with cytogenetically normal acute myeloid leukemia...
  89. pmc Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia
    Parvathi Ranganathan
    Division of Hematology, Department of Medicine, The Ohio State University, Columbus 43210, USA
    Blood 120:1765-73. 2012
    ..01). In summary, KPT-SINE are highly potent in vitro and in vivo in AML. The preclinical results reported here support clinical trials of KPT-SINE in AML...
  90. pmc The B-cell receptor signaling pathway as a therapeutic target in CLL
    Jennifer A Woyach
    Department of Internal Medicine, Division of Hematology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
    Blood 120:1175-84. 2012
    ..This review provides a summary of BCR signaling, tools for studying this pathway relevant to drug development in CLL, and early progress made with therapeutics targeting BCR-related kinases...
  91. pmc Complex karyotype predicts for inferior outcomes following reduced-intensity conditioning allogeneic transplant for chronic lymphocytic leukaemia
    Samantha M Jaglowski
    Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, USA
    Br J Haematol 159:82-7. 2012
    ..In patients with high-risk interphase cytogenetics, CK remained predictive of worse OS (P = 0·02) and EFS (P = 0·009). These findings support further evaluation of metaphase karyotype in transplant risk assessment...
  92. pmc Dual targeting of the cyclin/Rb/E2F and mitochondrial pathways in mantle cell lymphoma with the translation inhibitor silvestrol
    Lapo Alinari
    Department of Internal Medicine, College of Medicine, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
    Clin Cancer Res 18:4600-11. 2012
    ..We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression...
  93. pmc Pharmacokinetics and tissue disposition of lenalidomide in mice
    Darlene M Rozewski
    Division of Pharmaceutics, College of Pharmacy, 230 Parks Hall, 500W 12th Avenue, Columbus, Ohio 43210, USA
    AAPS J 14:872-82. 2012
    ..Atypical lenalidomide tissue distribution was observed in spleen and brain. The observed dose-dependent pharmacokinetics should be taken into consideration in translational and preclinical mouse studies...

Research Grants30

  1. Chicago Prevention and Intervention Epicenter (Chicago PIE)
    ROBERT ALAN WEINSTEIN; Fiscal Year: 2013
    ..The impact on ICU infection and prescribing characteristics of doctors will be assessed. To further assess the interventions, costs of averted outcomes and of the interventions will be compared. OPRIONAL OBEJCTIVE SCORE: 2 ..
  2. SPORE in Soft Tissue Sarcoma
    Samuel Singer; Fiscal Year: 2013
    ..abstract_text> ..