New agents in cancer clinical trials

Adams, Julian; Elliott, Peter J.

doi:10.1038/sj.onc.1204088

Cited by 81 publications

(57 citation statements)

References 63 publications

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“…One agent capable of blocking the classical NF-κB pathway is Bortezomib, a proteasome-inhibitor, which blocks proteasome-degradation of IκBα, allowing it to sequester NF-κB in the cytoplasm in an inactive state. 36 In this report, we demonstrate that Bortezomib inhibits the growth and induces apoptosis in PEL cell lines, which is associated with inhibition of the classical NF-κB pathway. Bortezomib has received FDA approval for the treatment of multiple myeloma, a disease that frequently demonstrates constitutive activity of the classical NF-κB pathway.…”

Section: Discussionmentioning

confidence: 94%

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

Matta¹,

Chaudhary²

2005

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 94%

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

Matta¹,

Chaudhary²

2005

Cancer Biology & Therapy

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“…IL-8 is the prototypical member of the C-X-C chemokine family and was initially identified as a chemo-attractant for neutrophils (Watanabe et al, 1989) but was subsequently shown to possess additional biological activities, including stimulation of angiogenesis and tumor growth (Koch et al, 1992;Sparmann and Bar-Sagi, 2004). In nude mice xenograft model system, IL-8 expression has been implicated in the initiation of tumor-associated inflammation and neovascularization and shown to directly correlate with metastatic potential (Adams and Elliott, 2000). A role for IL-8 in the pathogenesis of KS has been suggested by its high levels in the serum of KS patients as compared with matched controls and in the supernatant of AIDS-KS cell lines as compared with human umbilical vein endothelial cells (HUVECs) (Masood et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-κB activation

Sun

Matta

et al. 2006

Oncogene

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“…More recently, a series of dipeptide boronic acid analog proteasome inhibitors that specifically inhibit the chymotryptic enzyme activity of the proteasome have been synthesized (14,15). One of these, PS-341, is a low molecular weight, water-soluble dipeptide that targets the chymotryptic site in the 20S proteasome.…”

Section: Antle Cell Lymphoma (Mcl)mentioning

confidence: 99%

Inhibition of Constitutive NF-κB Activation in Mantle Cell Lymphoma B Cells Leads to Induction of Cell Cycle Arrest and Apoptosis

Pham

Tamayo

Yoshimura

et al. 2003

The Journal of Immunology

297

231

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Constitutive activation of the NF-κB has been documented to be involved in the pathogenesis of many human malignancies, including hemopoietic neoplasms. In this study, we examined the status of NF-κB in two non-Hodgkin’s lymphoma cell lines derived from mantle cell lymphoma (MCL) samples and in patient MCL biopsy specimens by EMSA and confocal microscopic analysis. We observed that NF-κB is constitutively activated in both the MCL cell lines and in the MCL patient biopsy cells. Since NF-κB has been shown to play an important role in a variety of cellular processes, including cell cycle regulation and apoptosis, targeting the NF-κB pathways for therapy may represent a rational approach in this malignancy. In the MCL cell lines, inhibition of constitutive NF-κB by the proteasome inhibitor PS-341 or a specific pIκBα inhibitor, BAY 11-7082, led to cell cycle arrest in G1 and rapid induction of apoptosis. Apoptosis was associated with the down-regulation of bcl-2 family members bcl-xL and bfl/A1, and the activation of caspase 3, that mediates bcl-2 cleavage, resulting in the release of cytochrome c from the mitochondria. PS-341or BAY 11-induced G1 cell cycle arrest was associated with the inhibition of cyclin D1 expression, a molecular genetic marker of MCL. These studies suggest that constitutive NF-κB expression plays a key role in the growth and survival of MCL cells, and that PS-341 and BAY 11 may be useful therapeutic agents for MCL, a lymphoma that is refractory to most current chemotherapy regimens.

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New agents in cancer clinical trials

Cited by 81 publications

References 63 publications

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

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

Induction of IL-8 expression by human herpesvirus 8 encoded vFLIP K13 via NF-κB activation

Inhibition of Constitutive NF-κB Activation in Mantle Cell Lymphoma B Cells Leads to Induction of Cell Cycle Arrest and Apoptosis

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