Table of Contents

Reviews

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  • Brooke B. Ancrile,
  • Kevin M. O’Hayer,
  • and Christopher M. Counter

  Oncogenic Ras–Induced Expression of Cytokines: A New Target of Anti-Cancer Therapeutics

  Mol Interv February 2008 8:22-27; doi:10.1124/mi.8.1.6
  • Abstract
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  Strategies to combat cancer have expanded beyond therapeutics that attack or exploit the basis of unfettered cell proliferation. In recent years, an increasing emphasis has been placed on understanding the in vivo environmental conditions that nourish or otherwise support tumor growth. GTPases of the RAS family are intracellular proteins that normally participate in the relay of signals from the exterior cell surface to the cell nucleus. These proteins are the product of RAS-encoding oncogenes, which become mutated in a significant portion of human cancers and thereby pervert intracellular signals involved in cell division. Intriguingly, RAS also appears to function in cancer by fostering communication among cells from distinct tissues, and this level of RAS-mediated paracrine signaling offers an exciting avenue for the development of anti-cancer drugs. Indeed, modern molecular tools and biologic-based therapeutics show promise in animal models and early translational studies.

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  • Karsten Gronert

  Lipid Autacoids in Inflammation and Injury Responses: A Matter of Privilege

  Mol Interv February 2008 8:28-35; doi:10.1124/mi.8.1.7
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  Vertebrate tissues that are exposed to the environment are thereby prone to injury, in which case cell growth and repair must be condoned, but invasion by pathogens must be prevented. Certain aspects of inflammation and wound healing thus rest in a curious balance, which if displaced can result in inflammatory disease or infection. The very tissues that experience this balance most precariously have long been recognized to possess a special resilience to injury and infection, and an understanding of this resilience may well inform ongoing clinical research that addresses many important immune and allergic responses. Lipid autacoids appear to provide a check on processes of inflammation, and investigation into their mechanisms of action reminds us that therapeutic interventions into inflammation must not subvert the programmatic resolution of a highly complex, fundamentally defensive, process.

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  • Robert A. Newman,
  • Peiying Yang,
  • Alison D. Pawlus,
  • and Keith I. Block

  Cardiac Glycosides as Novel Cancer Therapeutic Agents

  Mol Interv February 2008 8:36-49; doi:10.1124/mi.8.1.8
  • Abstract
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  Digoxin, digitoxin, and ouabain are well-known cardiac glycosides with a reputation as effective agents in the treatment of congestive heart failure and cardiac arrhythmia. Perhaps equally well known is their narrow therapeutic window: plasma concentrations of these drugs in patients must be carefully monitored to safeguard against toxic side effects. Less well known, however, is the emerging role of this category of compounds in the treatment of proliferative diseases such as cancer. Promising findings have shown these compounds to be involved in complex cell signal transduction mechanisms, resulting in the selective control of human tumor but not normal cellular proliferation. As such, they represent a promising form of targeted cancer chemotherapy. New clinical studies of their anticancer potential as single or adjuvant treatments may provide insight into these agents as potent therapeutic options.