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Biotech / Medical : Incyte (INCY) -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (2655)	5/11/2011 12:42:50 AM
From: software salesperson	Read Replies (1) \| Respond to of 3202

from 5/10 BofA presentation rationale for rux pancreatic cancer trial: 1) animal models show heightened sensitivity to apoptosis from chemotherapeutics when JAK pathway is taken out at the same time 2) penetrate tumor 3) prevent severe cachexia development it will be a P2b study that could be registrational the endpoint will be overall survival it will be for 2nd line capecitabine + rux vs. capecitabine sales

To: Biomaven who wrote (2655)	12/29/2011 4:03:45 PM
From: scaram(o)uche	Respond to of 3202

Proc Natl Acad Sci U S A. 2011 Dec 27. [Epub ahead of print] TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2. Delhase M, Kim SY, Lee H, Naiki-Ito A, Chen Y, Ahn ER, Murata K, Kim SJ, Lautsch N, Kobayashi KS, Shirai T, Karin M, Nakanishi M. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115. The decision between survival and death in cells exposed to TNF relies on a highly regulated equilibrium between proapoptotic and antiapoptotic factors. The TNF-activated antiapoptotic response depends on several transcription factors, including NF-?B and its RelA/p65 subunit, that are activated through phosphorylation-mediated degradation of I?B inhibitors, a process controlled by the I?B kinase complex. Genetic studies in mice have identified the I?B kinase-related kinase TANK-binding kinase 1 (TBK1; also called NAK or T2K) as an additional regulatory molecule that promotes survival downstream of TNF, but the mechanism through which TBK1 exerts its survival function has remained elusive. Here we show that TBK1 triggers an antiapoptotic response by controlling a specific RelA/p65 phosphorylation event. TBK1-induced RelA phosphorylation results in inducible expression of plasminogen activator inhibitor-2 (PAI-2), a member of the serpin family with known antiapoptotic activity. PAI-2 limits caspase-3 activation through stabilization of transglutaminase 2 (TG2), which cross-links and inactivates procaspase-3. Importantly, Tg2(-/-) mice were found to be more susceptible to apoptotic cell death in two models of TNF-dependent acute liver injury. Our results establish PAI-2 and TG2 as downstream mediators in the antiapoptotic response triggered upon TBK1 activation.