Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo

BACKGROUND: Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study. METHODS: We compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy) was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation. RESULTS: The in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression. CONCLUSION: This study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies

How firms grow: clustering as a dynamic model of internationalization

This paper provides a methodology for identifying the dynamics of international firm expansion, demonstrating systematic evidence of both ‘toe in the water’ and concentrated bursts of internationalization by US multinational enterprises. We use the methodology of statistical process control to analyze initial investments in host countries and develop a numerical measure of temporal clustering or bunching. Using this measure, we identify two distinct patterns of growth; whereas some firms cluster their investments over time, others do not cluster their investments. For firms that cluster, three types of clustering strategy are identified: concentrating, hibernating, and hybrid. Arguments based on internal firm architecture, experience, and learning are advanced to explain these findings. Journal of International Business Studies (2005) 36, 435–451. doi:10.1057/palgrave.jibs.8400140

Revisiting multinational firms' tolerance for joint ventures: a trust-based approach

In spite of the increasing popularity of international joint ventures, managers express a high level of dissatisfaction with them. This paper argues that overemphasis on the outcome has resulted in a neglect of the social processes underlying the outcome. The paper elaborates upon the rationale for a cooperative approach towards interorganizational collaborative relationships based on trust, and discusses it in the context of joint ventures. This is then applied towards understanding multinational ownership preferences and tolerance for joint ventures. It is argued that trust-centered logic is largely consistent with approaches that emphasize the issue of ownership, and deepens and enriches the insights provided by the latter. A shift in focus from ownership to relational dynamics is encouraged. Journal of International Business Studies (2006) 37, 30–43. doi:10.1057/palgrave.jibs.8400161

Experience, imitation, and the sequence of foreign entry: wholly owned and joint-venture manufacturing by South Korean firms and business groups in China, 1987–1995

The evolution of foreign entry in the form of joint ventures and wholly owned manufacturing operations is examined as a staged process shaped by experience and imitation dynamics at the firm, group, and industry levels of analysis. The expansion of South Korean firms into China between 1987 and 1995 lends support to the staged view of foreign entry. Over time, technology-intensive firms are more likely to abandon joint-venture entry modes, owing to contractual hazards. Firms in the same business group are found to imitate each other's choice of joint ventures and wholly owned plants. Firms in the same industry mimic each other's choice of wholly owned plants, though not of joint ventures. Journal of International Business Studies (2003) 34, 185–198. doi:10.1057/palgrave.jibs.8400016