The clinical manifestations of anti-cancer drug associated cardiac side effects are diverse and can range from acutely induced cardiac arrhythmias to severe contractile dysfunction, and potentially fatal heart failure. Anthracyclines and trastuzumab cardiac toxicity have been well described and left ventricular ejection fraction (LVEF) evaluation is commonly performed before their use. Bortezom...

PURPOSE To assess the safety of administering bortezomib to patients undergoing a radical prostatectomy, to assess pathologic changes induced by bortezomib in prostate cancer specimen, and to verify alterations by the drug in proteasome protein targets. EXPERIMENTAL DESIGN Bortezomib is a proteasome inhibitor that has shown activity in vitro and in vivo in prostate cancer. We performed a neoa...

To study the mechanism of acquired resistance to bortezomib, a new antitumor drug that is the first therapeutic proteasome inhibitor, we established a series of bortezomib-resistant T lymphoblastic lymphoma/leukemia cell lines, designated the JurkatBs, from the parental Jurkat line via repeated drug selection. There were no significant differences in the growth curves or colony formation betwee...

INTRODUCTION Bortezomib is a proteasome inhibitor that targets myeloma cell and its bone marrow microenvironment. Intravenous Bortezomib with or without dexamethasone, is effective and well tolerated in patients with relapsed/refractory multiple myeloma (MM). METHODS We used Bortezomib without corticosteroids, to avoid the risk of lung infection reactivations due to patient's Pseudomonas aeru...

We report preliminary observations on the efficacy of bortezomib in 20 patients with AL amyloidosis whose clonal disease was active despite treatment with a median of 3 lines of prior chemotherapy, including a thalidomide combination in all cases. Patients received a median of 3 (range 1-6) cycles of bortezomib and 9 (45%) patients received concurrent dexamethasone. Three (15%) patients achieve...

Dissociating graft-versus-tumor (GVT) effect from acute graft-versus-host disease (GVHD) still remains a great challenge in allogeneic bone marrow transplantation (allo-BMT). Bortezomib, a proteasome inhibitor, has shown impressive efficacy as a single agent in patients with hematologic malignancies but can result in toxicity when administered late after allogeneic transplantation in murine mod...

PURPOSE The proteasome inhibitor bortezomib inhibited cell growth and angiogenesis in neuroblastoma. Bortezomib has been shown to induce synergistic activity when combined with other antineoplastic agents. Here we have investigated the antitumor activity of bortezomib in combination with fenretinide, a synthetic retinoid, against neuroblastoma cells. EXPERIMENTAL DESIGN Different neuroblastom...

Chronic myeloid leukemia (CML) is treated effectively with tyrosine kinase inhibitors (TKIs); however, 2 key problems remain— the insensitivity of CML stem and progenitor cells to TKIs and the emergence of TKI-resistant BCR-ABL mutations. BCRABL activity is associated with increased proteasome activity and proteasome inhibitors (PIs) are cytotoxic against CML cell lines. We demonstrate that bor...

Although bortezomib is clinically approved for the treatment of mantle cell lymphoma (MCL), only limited effects of this treatment have been demonstrated. To improve survival for bortezomib-resistant patients, it is necessary to develop new therapeutic strategies. In the present study, we used biochemical and molecular methodologies to demonstrate that tissue transglutaminase (TG) activates dow...

Proteasome inhibitors are potent inducers of apoptosis in isolated lymphocytes from patients with chronic lymphocytic leukemia (CLL). However, the reversible proteasome inhibitor bortezomib (PS-341; Velcade) did not display substantial antitumor activity in CLL patients. Here, we compared the effects of bortezomib and a new irreversible proteasome inhibitor (NPI-0052) on 20S chymotryptic protea...