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Title: Enhancing or eliminating signals for cell survival to treat disease. Author: Tweardy DJ, Jing N. Journal: Trans Am Clin Climatol Assoc; 2006; 117():33-51; discussion 51-2. PubMed ID: 18528463. Abstract: Approximately half of all medical illnesses can be attributed to insufficient or excessive apoptosis. Apoptosis resistance is a cardinal feature of cancer, mediated in many instances, by signal transducer and activator of transcription (STAT) 3. We identified G-quartet oligodeoxynucleotides (GQ-ODNs) as potent and selective inhibitors of Stat3 DNA binding activity in vitro. We report here that GQ-ODNs are capable of inhibiting the growth of nude mouse xenografts of breast and prostate tumors. We developed a rat model of severe hemorrhagic shock (HS) to assess the benefits of promoting Stat3 activity in diseases marked by excessive apoptosis. Administration of the Stat3-activating cytokine IL-6 at the initiation of resuscitation from HS activated intra-cardiac Stat3, reversed cardiac apoptosis, left ventricular dysfunction and hypovolemic circulatory collapse (HCC) and resulted in a 5-fold reduction in mortality; pre-treatment of rats with GQ-ODN prevented the reversal of cardiac apoptosis and HCC by IL-6. Thus, targeting of Stat3 may be a useful for treatment of multiple cancers; agents that activate Stat3 may be beneficial in acute insults that cause apoptosis in organs critical for survival.[Abstract] [Full Text] [Related] [New Search]