Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Millennium Pharmaceuticals, Inc. (MLNM) -- Ignore unavailable to you. Want to Upgrade?

To: Icebrg who wrote (1646)	6/20/2003 11:11:41 AM
From: tuck	Respond to of 3044

>>The Journal of Immunology, 2003, 171: 88-95. Inhibition of Constitutive NF-B Activation in Mantle Cell Lymphoma B Cells Leads to Induction of Cell Cycle Arrest and Apoptosis1 Lan V. Pham, Archito T. Tamayo, Linda C. Yoshimura, Piao Lo and Richard J. Ford2 Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 Constitutive activation of the NF-B 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-B 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-B is constitutively activated in both the MCL cell lines and in the MCL patient biopsy cells. Since NF-B has been shown to play an important role in a variety of cellular processes, including cell cycle regulation and apoptosis, targeting the NF-B pathways for therapy may represent a rational approach in this malignancy. In the MCL cell lines, inhibition of constitutive NF-B by the proteasome inhibitor PS-341 or a specific pIB 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-B 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. << Cheers, Tuck