Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma

Jakob, Christian; Egerer, Karl; Liebisch, Peter; Türkmen, Seval; Zavrski, Ivana; Kuckelkorn, Ulrike; Heider, Ulrike; Kaiser, Martin; Fleissner, Claudia; Sterz, Jan; Kleeberg, Lorenz; Feist, Eugen; Burmester, Gerd R.; Kloetzel, Peter M.; Sezer, Orhan

doi:10.1182/blood-2006-04-016360

Cited by 118 publications

(107 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Circulating proteasome levels were found to be an independent prognostic factor for survival in previously untreated patients with multiple myeloma. 30 Bortezomib (PS-341), 31 that is the first proteasome inhibitor approved by the Food and Drug Administration, was shown to induce the stabilization of I-kB, 32 c-Fos and c-Jun. 33,34 In multiple myeloma, the major effects of bortezomib were contributed to the inhibition of NF-kB activation.…”

Section: Introductionmentioning

confidence: 99%

Bortezomib inhibits human osteoclastogenesis

et al. 2007

View full text Add to dashboard Cite

In multiple myeloma, the overexpression of receptor activator of nuclear factor kappa B (NF-jB) ligand (RANKL) leads to the induction of NF-jB and activator protein-1 (AP-1)-related osteoclast activation and enhanced bone resorption. The purpose of this study was to examine the molecular and functional effects of proteasome inhibition in RANKL-induced osteoclastogenesis. Furthermore, we aimed to compare the outcome of proteasome versus selective NF-jB inhibition using bortezomib (PS-341) and I-jB kinase inhibitor PS-1145. Primary human osteoclasts were derived from CD14 þ precursors in presence of RANKL and macrophage colony-stimulating factor (M-CSF). Both bortezomib and PS-1145 inhibited osteoclast differentiation in a dose-and time-dependent manner and furthermore, the bone resorption activity of osteoclasts. The mechanisms of action involved in early osteoclast differentiation were found to be related to the inhibition of p38 mitogenactivated protein kinase pathways, whereas the later phase of differentiation and activation occurred due to inhibition of p38, AP-1 and NF-jB activation. The AP-1 blockade contributed to significant reduction of osteoclastic vascular endothelial growth factor production. In conclusion, our data demonstrate that proteasomal inhibition should be considered as a novel therapeutic option of cancer-induced lytic bone disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Bortezomib inhibits human osteoclastogenesis

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Bortezomib is used in the treatment of multiple myeloma (Fisher et al, 2006). Notably, multiple myeloma has been observed to result in increased proteasome levels in blood serum that decrease to normal levels in response to successful chemotherapy (Jakob et al, 2007). Studies in animals have indicated that bortezomib may also have clinically significant effects in pancreatic cancer (Nawrocki et al, 2004;Shah et al, 2001).…”

Section: Proteasomementioning

confidence: 99%

DNA Repair, Cancer and Cancer Therapy

Wang¹

2011

DNA Repair and Human Health

View full text Add to dashboard Cite

“…Proteasomes are highly expressed in transformed cells contributing to the aggressive growth of cancer cells. 25,26 Though this mechanism is incompletely understood, it seems to involve the rapid degradation of cell cycle and pro-apoptotic proteins, mediated primarily through the destabilization of TP53 and NFκB (reviewed in ref. 27).…”

confidence: 99%