The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells

BACKGROUND: With the emergence of Src inhibitors in clinical trials, improved knowledge of the molecular responses of cancer cells to these agents is warranted. This will facilitate the development of tests to identify patients who may benefit from these agents, allow drug activity to be monitored and rationalize the combination of these agents with other treatment modalities. METHODS: This study evaluated the molecular and functional effects of Src inhibitor AZD0530 in human lung cancer cells, by Western blotting and reverse transcription-polymerase chain reaction, and by assays for cell viability, migration, and invasion. RESULTS: Src was activated in four of five cell lines tested and the level corresponded with the invasive potential and the histologic subtype. Clinically relevant, submicromolar concentrations of AZD0530 blocked Src and focal adhesion kinase, resulting in significant inhibition of cell migration and Matrigel invasion. Reactivation of STAT3 and up-regulation of JAK indicated a potential mechanism of resistance. AZD0530 gave a potent and sustained blockage of AKT and enhanced the sensitivity to irradiation. CONCLUSIONS: The results indicated that AZD0530, aside from being a potent inhibitor of tumor cell invasion which could translate to inhibition of disease progression in the clinic, may also lower resistance of lung cancer cells to pro-apoptotic signals.

Book review of “Germany in Transit: Nation and Migration, 1955-2005”. 588 pages, University of California Press, 2007, by Deniz Göktürk, David Gramling and Anton Kaes (eds.)

Though migration is an age-old feature of human activity, driven by various circumstances, its current place in the midst of global dynamics and the phenomenon of globalization is becoming increasingly critical. International immigration and its regulation have been largely shaped by the policies in the receiving countries, often determining preferences for nationality cohorts and work skills to satisfy their labor and human capital requirements. When immigration has been necessitated by political strife, host countries have displayed immense magnanimity as well. However, the growing realization of resource limitations and the strange quirks of cultural pluralism are in turn creating waves of dissonance. Literature and the media are now replete with an in depth look into the immigration debate in various nations of the world in trying to seek new directions and satisfactory solutions.