Lung cancer causes more than 140,000 deaths annually in the United States alone, and the prognosis for non-small cell lung cancer (NSCLC) is particularly poor. Therapies using small molecules that preferentially kill lung tumor cells by inducing cellular suicide (apoptosis) would therefore be highly desirable. Retinoids have shown promise as cancer preventive and cancer therapeutic agents. Retinoid signals are mediated by two classes of nuclear receptors: the retinoic acid receptors (RAR alpha, beta, and gamma) and the retinoid X receptors (RXR alpha, beta and gamma). These receptors usually bind as heterodimers to specific DNA sequences and/or interact with other transcriptional regulators, such as AP-1 (ref. 10) to regulate gene transcription. Synthetic retinoids can be made that activate only specific portions of the complex retinoid response network and activate selective biological programs. To identify retinoids with novel biological activities, we used a high-throughput "biological activity fingerprint" screen on a large library of retinoids and retinoid-related molecules (RRMs). We identified new structures that are highly effective against lung cancer cells in vitro, inducing apoptosis. We show here for one of these compounds that it is very effective against a human NSCLC in vivo in an animal model. These new molecules show a distinct pattern of receptor signaling.

The security dilemma is one of the most important theoretical ideas in international relations.1 In the years since Herbert Butterfield, John Herz, and Robert Jervis first developed the concept, 2 it has been extended and applied to "address many of the most important questions of international relations Shiping Tang is Professor at the School of International Relations and Public Affairs (SIRPA), Fudan University, Shanghai, China. Prior to his current appointment, he was Senior Fellow at the S. Rajaratnam School of International Studies, Nanyang Technological University, Singapore, where this article was finished.I thank Stephen Van Evera, two anonymous reviewers, and the editors of Security Studies for their perceptive criticism and suggestions. I also thank Alan Collins, Robert Jervis, Stuart Kaufman, Andrew Kydd, Ned Lebow, Barry Posen, Robert Powell, Randall Schweller, and Stephen Van Evera for responding to a survey on the security dilemma. Beatrice Bieger provided excellent assistance on the bibliography. I dedicate this article to Robert Jervis, on the thirtieth anniversary of his seminal article, "Cooperation Under the Security Dilemma." 1 I differentiate the term "security dilemma" from "security dilemma theory." The security dilemma is a concept for labeling a particular situation in international politics. Security dilemma theory is the body of knowledge that seeks to understand the underlying causes, regulations, and implications of the security dilemma. I also differentiate the security dilemma from its close relative-spiral. Also, we should differentiate a spiral from the spiral model.

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