The proteasome inhibitor bortezomib (PS-341) inhibits growth and induces apoptosis in primary effusion lymphoma cells

Matta, Hittu; Chaudhary, Preet M.

doi:10.4161/cbt.4.1.1379

Cited by 66 publications

(56 citation statements)

References 34 publications

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“…A major mechanism of action for bortezomib is inactivation of nuclear factor (NF)-B, via stabilization of the NF-B inhibitor IB [9 -14], which contributes to apoptosis, cell cycle or growth arrest, and stress response. Bortezomib also enhances apoptosis by promoting the release of cytochrome C [15], stimulating generation of reactive oxygen species [16], upregulating the tumor suppressor protein p53 and the two inhibitors of cyclin-dependent kinase (CDK), p21 and p27 [11, 13, 15], and increasing expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors [17]. Bortezomib may also have numerous effects on the B-cell lymphoma 2 (Bcl-2) family of proteins, including activation of proapoptotic Bcl-2 proteins [10, 15, 16, 18] and inhibition of antiapoptotic Bcl-2 proteins [9, 16, 18].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

2012

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Although patients with B-cell non-Hodgkin's lymphoma (NHL) usually respond to initial conventional chemotherapy, they often relapse and mortality has continued to increase over the last three decades in spite of salvage therapy or high dose therapy and stem cell transplantation. Outcomes vary by subtype, but there continues to be a need for novel options that can help overcome chemotherapy resistance, offer new options as consolidation or maintenance therapy postinduction, and offer potentially less toxic combinations, especially in the elderly population. The bulk of these emerging novel agents for cancer treatment target important biological cellular processes. Bortezomib is the first in the class of proteasome inhibitors (PIs), which target the critical process of intracellular protein degradation or recycling and editing through the proteasome. Bortezomib is approved for the treatment of relapsed or refractory mantle cell lymphoma.The mechanisms of proteasome inhibition are very complex by nature (because they affect many pathways) and not fully understood. However, mechanisms of action shared by bortezomib and investigational PIs such as carfilzomib, marizomib, ONX-0912, and MLN9708 are distinct from those of other NHL treatments, making them attractive options for combination therapy. Preclinical evidence suggests that the PIs have additive and/or synergistic activity with a large number of agents both in vitro and in vivo, from cytotoxics to new biologicals, supporting a growing number of combination studies currently underway in NHL patients, as reviewed in this article. The results of these studies will help our understanding about how to best integrate proteasome inhibition in the management of NHL and continue to improve patient outcomes. The Oncologist 2012; 17:694 -707 OVERVIEWIn the U.S., Ͼ70,000 patients are diagnosed with non-Hodgkin's lymphoma (NHL) annually [1], and one in three patients dies within 5 years of diagnosis [2]. Of note, the incidence of NHL has increased dramatically (Ͼ80% over the last three decades). The broad spectrum of malignancies comprising NHL can be classified according to cell of origin (B, T, or natural killer cell), as well as mature or immature phenotype, as seen in the World Health Organization classification (Table 1) [3,4].The distribution of the different subtypes of NHL varies geographically worldwide.Response rates to conventional chemotherapy are typically Ͼ50%, and many patients achieve a complete response (CR). Even so, most patients eventually relapse [5], and there is no generally accepted therapeutic approach for relapsed or refractory lymphoma the objective response rate (ORR) and CR rate and has been the main improvement in the treatment of B-cell NHL during the last three decades. Though it varies with B-cell NHL subtype, a significant number of patients relapse with no greatly defined standard therapies. For DLBCL, the combination of high-dose chemotherapy and stem cell transplantation is effective for relapsed NHL [7] but is clearly worse in p...

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Section: Mechanisms Of Actionmentioning

confidence: 99%

Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

2012

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“…Both therapies have been shown to induce apoptosis in PEL cell lines (25,26). Matta demonstrated that the activity of bortezomib was associated with inhibition of nuclear factor kappa-B pathways, upregulation of p53, p21, and p27, and activation of the caspase cascade (27). Bortezomib was also shown to work synergistically with cytotoxic chemotherapy on PEL cell lines.…”

Section: Discussionmentioning

confidence: 94%

Primary Effusion Lymphoma Diagnosed by Pericardiocentesis

Nemunaitis¹,

Schussler²,

Shiller³

et al. 2009

Baylor University Medical Center Proceedings

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“…In vitro, the combination of bortezomib with doxorubicin (An et al, 2004;Matta & Chaudhary, 2005) or dexamethasone (An et al, 2004) exerted additive or synergistic inhibitory effects on PEL cell growth. Some authors found that the synergistic effects were schedule-dependent and only observed when bortezomib was used prior to doxorubicin, and simultaneously or prior to dexamethasone (An et al, 2004).…”

Section: Correspondence ª 2008 the Authorsmentioning

confidence: 99%

“…Recently, the proteasome inhibitor bortezomib (PS-341) has been shown to inhibit cell growth and induce apoptosis of PEL cell lines (An et al, 2004;Matta & Chaudhary, 2005;Abou-Merhi et al, 2007). This antitumour effect resulted from the inhibition of the nuclear factor-jB pathway, which is constitutively activated in PEL, and critical for PEL cell survival (Keller et al, 2000).…”

Section: Correspondence ª 2008 the Authorsmentioning

confidence: 99%

Bortezomib (PS‐341) in patients with human herpesvirus 8‐associated primary effusion lymphoma

Boulanger¹,

Meignin²,

Oksenhendler³

2008

Br J Haematol

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The proteasome inhibitor bortezomib (PS-341) inhibits growth and induces apoptosis in primary effusion lymphoma cells

Cited by 66 publications

References 34 publications

Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

Primary Effusion Lymphoma Diagnosed by Pericardiocentesis

Bortezomib (PS‐341) in patients with human herpesvirus 8‐associated primary effusion lymphoma

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