Research Topics
| R Z OrlowskiSummaryAffiliation: University of North Carolina Country: USA Publications
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Detail Information
Publications
Tumor growth inhibition induced in a murine model of human Burkitt's lymphoma by a proteasome inhibitorR Z Orlowski
The Johns Hopkins Oncology Center, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cancer Res 58:4342-8. 1998..These results, showing a 42% tumor growth delay, indicate that proteasome inhibitors have the potential of curbing the growth of a c-myc-related tumor...- Bortezomib and its role in the management of patients with multiple myelomaRobert Z Orlowski
University of North Carolina at Chapel Hill, 22 003 Lineberger Comprehensive Cancer Center, CB 7295, Mason Farm Road, Chapel Hill, NC 27599 7295, USA
Expert Rev Anticancer Ther 4:171-9. 2004..Bortezomib may provide significant benefits to patients both alone and in combination with other agents and at several time points during the natural history of multiple myeloma... - 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.... 
The role of the ubiquitination-proteasome pathway in breast cancer: applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancerRobert Z Orlowski
The Department of Medicine, Division of Hematology Oncology, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA
Breast Cancer Res 5:1-7. 2003..Such drugs, alone and especially in combination with current chemotherapeutics, may well represent important advances in the therapy of patients with breast cancer...- Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignanciesRobert Z Orlowski
Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina at Chapel Hill, 27599 7295, USA
J Clin Oncol 20:4420-7. 2002..To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacodynamics (PD) of the proteasome inhibitor bortezomib (previously known as PS-341) in patients with refractory hematologic malignancies... - Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignanciesRobert Z Orlowski
Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
Blood 105:3058-65. 2005..Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen... - Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progressionRobert Z Orlowski
Department of Medicine, Division of Hematology Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
J Clin Oncol 25:3892-901. 2007..This phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma... - Evidence that inhibition of p44/42 mitogen-activated protein kinase signaling is a factor in proteasome inhibitor-mediated apoptosisRobert Z Orlowski
Lineberger Comprehensive Cancer Center and Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
J Biol Chem 277:27864-71. 2002..These studies support a role for inactivation of signaling through the p44/42 MAPK pathway in proteasome inhibitor-mediated apoptosis... - Targeting the proteasome as a therapeutic strategy against haematological malignanciesRobert Z Orlowski
Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
Expert Opin Investig Drugs 15:117-30. 2006..The current state of knowledge about the activity of bortezomib, both alone and in combination with standard chemotherapeutics, as part of the emerging armamentarium against haematological malignancies is reviewed... - The role of the ubiquitin-proteasome pathway in apoptosisR Z Orlowski
The Department of Medicine, Division of Hematology Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Cell Death Differ 6:303-13. 1999..This review provides a summary of the experimental basis by which components of the ubiquitin-proteasome pathway have been linked to apoptosis, and attempts are made to formulate a hypothesis about its role in this process... - Successful pregnancy after cladribine therapy for hairy cell leukemiaRobert Z Orlowski
The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
Leuk Lymphoma 45:187-8. 2004..In this report, the first case of a patient diagnosed with HCL who then went on to a successful pregnancy is described, suggesting that fertility may be preserved in at least some female patients treated with this agent... 
Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myelomaDeborah J Kuhn
Lineberger Comprehensive Cancer Center and Department of Medicine, Division of Hematology Oncology, University of North Carolina, Chapel Hill, NC, USA
Blood 110:3281-90. 2007..Carfilzomib also overcame resistance to other conventional agents and acted synergistically with dexamethasone to enhance cell death. Taken together, these data provide a rationale for the clinical evaluation of carfilzomib in MM...- The proteasome as a target for cancer therapyPeter M Voorhees
The Lineberger Comprehensive Cancer Center, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA
Clin Cancer Res 9:6316-25. 2003..Below we discuss the rationale behind targeting the proteasome for cancer therapy, and review the preclinical and clinical data on proteasome inhibitors alone, and in combination with conventional chemotherapeutics... - Bortezomib therapy following first relapseRobert Z Orlowski
The Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Chapel Hill, North Carolina, USA
Oncology (Williston Park) 19:23-6. 2005 - Evidence that mitogen-activated protein kinase phosphatase-1 induction by proteasome inhibitors plays an antiapoptotic roleGeorge W Small
The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
Mol Pharmacol 66:1478-90. 2004..Furthermore, they suggest that a proteasome inhibitor/anthracycline regimen holds potential for enhanced antitumor activity in part through repression of MKP-1, supporting clinical evaluation of such combinations... - Repression of mitogen-activated protein kinase (MAPK) phosphatase-1 by anthracyclines contributes to their antiapoptotic activation of p44/42-MAPKGeorge W Small
University of North Carolina at Chapel Hill, 22-003 Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7295, USA
J Pharmacol Exp Ther 307:861-9. 2003..These studies support the ability of anthracyclines to activate antiapoptotic p44/42-MAPK phosphorylation in breast cancer, and indicate that this occurs in part through the novel mechanism of repression of MKP-1 transcription... - Proteasome inhibitors induce a p38 mitogen-activated protein kinase (MAPK)-dependent anti-apoptotic program involving MAPK phosphatase-1 and Akt in models of breast cancerYue Y Shi
22-003 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB # 7295, Mason Farm Road, Chapel Hill, NC 27599-7295, USA
Breast Cancer Res Treat 100:33-47. 2006..Further, they suggest that strategies targeting MKP-1 and Akt could enhance the anti-tumor efficacy of proteasome inhibitors against breast cancer... - Emerging role of novel combinations for induction therapy in multiple myelomaPeter M Voorhees
Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, NC 27599 7305, USA
Clin Lymphoma Myeloma 7:33-41. 2006..Herein we review the early promising clinical activity of these regimens in patients with newly diagnosed MM... - Bronchiolitis obliterans with organizing pneumonia after rituximab therapy for non-Hodgkin's lymphomaSuzanne E Biehn
University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 7295, USA
Hematol Oncol 24:234-7. 2006..Physicians utilizing rituximab should be aware of this association given the difficulty of differentiating between presentations of BOOP and neoplastic pulmonary processes... - Extended follow-up of outcome measures in multiple myeloma patients treated on a phase I study with bortezomib and pegylated liposomal doxorubicinSuzanne E Biehn
University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA
Ann Hematol 86:211-6. 2007.... - Targeting the ubiquitin-proteasome pathway in breast cancer therapyE Claire Dees
Department of Medicine, Division of Hematology/Oncology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA
Future Oncol 2:121-35. 2006.... - Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell deathPeter M Voorhees
Department of Medicine, Division of Haematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7305, USA
Br J Haematol 145:481-90. 2009..Taken together, our data provide a strong rationale for the clinical development of the CNTO 328/dex regimen for patients with myeloma... - The proteasome and proteasome inhibitors in cancer therapyPeter M Voorhees
Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
Annu Rev Pharmacol Toxicol 46:189-213. 2006.... - Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myelomaPeter M Voorhees
Division of Hematology Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7305, USA
Clin Cancer Res 13:6469-78. 2007.... - Emerging data on the use of anthracyclines in combination with bortezomib in multiple myelomaPeter M Voorhees
Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, NC 27599, USA
Clin Lymphoma Myeloma 7:S156-62. 2007..Herein, we review the preclinical data supporting the use of bortezomib with anthracyclines and the promising clinical data with these combinations... - Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagyQing Chen
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA
Blood 111:4690-9. 2008..These findings provide a rational framework for further development of SCF(Skp2) inhibitors as a novel class of antitumor agents... - Proteasome inhibitors in cancer therapyRobert Z Orlowski
The Department of Medicine and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA
Methods Mol Biol 301:339-50. 2005.... 
A phase I and pharmacologic study of the combination of bortezomib and pegylated liposomal doxorubicin in patients with refractory solid tumorsE Claire Dees
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Cancer Chemother Pharmacol 63:99-107. 2008..We conducted a phase I trial of bortezomib and pegylated liposomal doxorubicin (PLD) in patients with refractory solid tumors...- Clinical course of thrombocytopenia in patients treated with imatinib mesylate for accelerated phase chronic myelogenous leukemiaHendrik W van Deventer
Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Rm 3009 Old Clinic Building, Chapel Hill, NC 27599 7305, USA
Am J Hematol 71:184-90. 2002..Grade III-IV thrombocytopenia is common in accelerated phase CML and may be a marker for the inability to achieve cytogenetic response using single agent imatinib mesylate... - Evidence for involvement of calpain in c-Myc proteolysis in vivoGeorge W Small
The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Arch Biochem Biophys 400:151-61. 2002..These studies support a role for calpain in the control of c-Myc levels in vivo, and suggest that mutations impacting on sensitivity to calpain may contribute to c-Myc-mediated tumorigenesis... - Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancerSivagurunathan Somasundaram
The Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA
Cancer Res 62:3868-75. 2002.... - Mitogen-activated protein kinase phosphatase-1 is a mediator of breast cancer chemoresistanceGeorge W Small
The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Cancer Res 67:4459-66. 2007.... - NF-kappaB as a therapeutic target in cancerRobert Z Orlowski
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7295, USA
Trends Mol Med 8:385-9. 2002..However, as there is currently no drug that blocks specific NF-kappaB activation, conclusions drawn with small-molecule inhibitors must be interpreted carefully... - Tumor induction by the c-Myc target genes rcl and lactate dehydrogenase AB C Lewis
Program in Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cancer Res 60:6178-83. 2000..These findings confirm Rcl and LDH-A as critical components of the cell transformation program induced by c-Myc and suggest that Rcl is tumorigenic in cells that are provided with a permissive metabolic milieu... - Proteasome inhibitors in cancer therapy: lessons from the first decadeRobert Z Orlowski
Department of Lymphoma Myeloma, Division of Cancer Medicine, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Clin Cancer Res 14:1649-57. 2008..This saga provides a salient example of the promise of translational medicine and a paradigm by which other agents may be successfully brought from the bench to the bedside... - Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapyPieter Sonneveld
Department of Hematology, Erasmus Medical Center, Rotterdam, Netherlands
Cancer 112:1529-37. 2008.... - A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumorsDavid P Ryan
Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
Cancer 107:2688-97. 2006..The authors conducted a Phase I dose-finding trial to study the use of combined bortezomib plus irinotecan in patients with advanced solid tumors... - Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomibPaul G Richardson
Dana Farber Cancer Institute, Brigham and Women s Hospital, 44 Binney St, Dana 1B02, Boston, MA 02115, USA
J Clin Oncol 24:3113-20. 2006..To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma... - A practical update on the use of bortezomib in the management of multiple myelomaJesus San Miguel
Hematology Department, Hospital Clinico Universitario de Salamanca, Servicio de Hematologia, Paseo de San Vicente 58, Salamanca E 37007, Spain
Oncologist 11:51-61. 2006..Information is given on the practical management of the most common adverse events, including peripheral neuropathy and thrombocytopenia, and the use of bortezomib in renal and hepatic impairment... - Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancerBhuvaneswari Ramaswamy
Division of Hematology/Oncology and Comprehensive Breast Health Services, Ohio State University Medical Center, Columbus, OH, USA
Breast Cancer Res Treat 93:67-74. 2005..To our knowledge, this is first description of docetaxel-induced activation of mitogen-activated and stress-activated protein kinase pathways in human breast cancer... - Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myelomaSagar Lonial
Winship Cancer Institute, Emory University, Atlanta, GA, USA
Blood 106:3777-84. 2005..The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production... - Bortezomib in recurrent and/or refractory multiple myeloma. Initial clinical experience in patients with impared renal functionSundar Jagannath
Blood Stem Cell and Bone Marrow Transplantation, St Vincent s Comprehensive Cancer Center, New York, New York 10011 8202, USA
Cancer 103:1195-200. 2005..Bortezomib is a potent, reversible proteasome inhibitor that has been approved for the treatment of recurrent and/or refractory multiple myeloma, but its activity in patients with renal impairment has not been studied to date... - A phase 2 study of bortezomib in relapsed, refractory myelomaPaul G Richardson
Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
N Engl J Med 348:2609-17. 2003..Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity... - Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphomaRichard J Jones
Department of Lymphoma and Myeloma, University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
Clin Cancer Res 14:5416-25. 2008..The ubiquitin-proteasome pathway has been validated as a target in non-Hodgkin's lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib... - American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myelomaRobert A Kyle
Dana Farber Cancer Institute, Boston, MA, USA
J Clin Oncol 25:2464-72. 2007..To update the recommendations for the use of bisphosphonates in the prevention and treatment of bone disease in multiple myeloma. The Update Committee expanded the guideline to include a discussion of osteonecrosis of the jaw (ONJ)...