To: zeta1961 who wrote (719 ) 4/25/2007 2:48:24 PM From: Jibacoa Read Replies (1) | Respond to of 802 Another note on INGN 241Preclinical Studies Identify Novel Approach for Enhancing the Anticancer Activity of Introgen's INGN 241 Wednesday April 25, 2:30 pm ET Data Published in Molecular Cancer Therapeutics AUSTIN, Texas--(BUSINESS WIRE)--Introgen Therapeutics, Inc. (NASDAQ:INGN - News) today announced the publication of new preclinical data describing how an intrinsic cell survival pathway impacts the anticancer activity of INGN 241. Inhibition of this pathway, known as NF-kB, enhanced the tumor killing effects of INGN 241 in cell culture and in preclinical models of human tumors. Researchers at Introgen and The University of Texas M. D. Anderson Cancer Center conducted the studies and the data appear in the current issue of Molecular Cancer Therapeutics."These studies demonstrate that mda-7, the active component of INGN 241, activates NF-kB in lung tumor cells," said Rajagopal Ramesh, PhD, associate professor in the Department of Thoracic and Cardiovascular Surgery at M. D. Anderson Cancer Center and principal author on the study. "Although the potent effects of mda-7 ultimately overcome NF-kB and lead to cancer cell death, these studies show that inhibition of NF-kB enhances the anti-cancer activity of INGN 241. This suggests that combining INGN 241 with NF-kB inhibitors could yield improved clinical effects. Many pharmaceutical companies are actively developing drugs targeting NF-kB, and these agents should enhance activity of INGN 241." A variety of chemotherapies and cytokines used in the treatment of cancer are known to activate NF-kB signaling. The current studies were undertaken to assess if INGN 241 had a similar effect. Results of tissue culture studies indicated that NF-kB levels in lung cancer cells were higher following administration of INGN 241 compared with controls and increased in a time-dependent manner. Additional cell culture analyses demonstrated that INGN 241 inhibited cell proliferation in cells with activated NF-kB, and that this effect was enhanced with inhibition of NF-kB. INGN 241 activity also was enhanced in animal models of lung tumors engineered to inhibit NF-kB activation. The studies also identified two other proteins, MEKK1 and caspase-3, which mediate the cell-killing effects of INGN 241. Based on these results, it is anticipated that the combination of INGN 241 and inhibitors of NF-kB will have an enhanced therapeutic effect and be suitable for clinical evaluation. Snip Bernard