BACKGROUND Although current chemotherapy using bortezomib (Velcade) against multiple myeloma in adults has achieved significant responses and even remission, a majority of patients will develop acquired resistance to bortezomib. Increased thioredoxin level has been reported to be associated with carcinogenesis; however, the role of thioredoxin in bortezomib drug resistance of myeloma remains un...

Multiple myeloma is a malignant still incurable plasma cell disorder. Pharmacological treatment based on proteasome inhibition has improved patient outcome; however, bortezomib-resistance remains a major clinical problem. Inhibition of proteasome functionality affects cellular iron homeostasis and iron is a potent inducer of reactive oxygen species and cell death, unless safely stored in ferrit...

The purpose of the present study was to evaluate the potency of the proteasome inhibitor bortezomib +/- gemcitabine in vitro and in vivo in pancreatic carcinoma. It could be shown that bortezomib induced apoptosis and inhibited proliferation of pancreatic carcinoma very efficiently in vitro. In contrast, in an orthotopic pancreatic adenocarcinoma mouse model, gemcitabine treatment inhibited tum...

The proteasome inhibitor bortezomib is an effective anti-cancer agent for the plasma cell malignancy multiple myeloma but clinical response is hindered by the emergence of drug resistance through unknown mechanisms. Drug sensitive myeloma cells were exposed to bortezomib to generate drug resistant cells that displayed a significant increase in subunits of the energy sensor AMP-activated protein...

Bortezomib (Velcade) is used widely for the treatment of various human cancers; however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that bortezomib induces proteasome-independent degradation of the TRAF6 protein, but not mRNA, in myelodysplastic syndrome (MD...

Bortezomib is an antitumor drug that competitively inhibits proteasome beta-1 and beta-5 subunits. While the impact of bortezomib on protein stability is known, the effect of this drug on intracellular peptides has not been previously explored. A quantitative peptidomics technique was used to examine the effect of treating human embryonic kidney 293T (HEK293T) cells with 5-500 nM bortezomib for...

Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and per...

BACKGROUND Inhibition of the proteasome-ubiquitin pathway has shown to exert growth inhibitory effects on several human carcinoma cell lines. In this study, the influence of bortezomib on human neuroblastoma cells was investigated. MATERIALS AND METHODS Cell proliferation of seven human neuroblastoma cell lines under bortezomib treatment was assessed by a colorimetric XTT-based assay. Subsequ...

BACKGROUND Bortezomib is widely used for the treatment of multiple myeloma. Bone marrow stromal cells (BMSCs) endow myeloma cells with survival and growth advantages. However, the influence of bortezomib on BMSCs is not well elucidated. We examined the effects of bortezomib on the survival and growth of BMSCs in vitro. METHODS The effects of bortezomib on the survival and proliferation of the...

The proteasome inhibitor bortezomib (PS-341/Velcade) is used for the treatment of relapsed and refractory multiple myeloma and mantle-cell lymphoma. We recently reported its therapeutic potential against natural killer (NK)-cell neoplasms. Here, we investigated the molecular mechanisms of bortezomib-induced cell death in NK lymphoma cells. NK lymphoma cell lines (SNK-6 and NK-YS) and primary cu...