The determinants of offshore production by Multinational Corporations (MNCs) : a comparison of Japanese and US MNCs

This study employs confidential affiliate-level panel data to improve measures of foreign affiliate activities of Japanese firms in manufacturing sectors. Combining existing data on U.S. MNCs with the Japanese data, we illustrate the pattern and determinant of their foreign affiliate sales by destination market across countries and industries for the period 1989-2005. Among our results, Japanese and U.S. MNCs are similar in the substantial growth of their foreign affiliate sales and the importance of sales to local markets. However, Japanese MNCs are distinctive from U.S. MNCs in that Japanese affiliate sales in Asia were prominently higher in host markets with lower educational attainment.Japan, United States, International business enterprises, Industrial management, Multinational firm, FDI, U.S., Skill endowment

Reconsidering the Backward Vertical Linkages of Foreign Affiliates: Evidence from Japanese Multinationals

This paper examines the determinants of the backward vertical linkages of Japanese foreign affiliates in manufacturing for the period 1994-2000, focusing on the local backward linkages, or local procurements in the host country. Our major findings are twofold. First, the unobserved affiliate-specific characteristics explain the large part of the variation of the backward linkages among foreign affiliates. Second, the experience of the affiliate has positive and sometimes non-linear impacts on local procurements for the affiliates, especially in Southeast Asia and China.Vertical Backward Linkages, Foreign Direct Investment, Local Procurements, Southeast Asia, China

The determinants of offshore production by Multinational Corporations (MNCs) : a comparison of Japanese and US MNCs

This study employs confidential affiliate-level panel data to improve measures of foreignaffiliate activities of Japanese firms in manufacturing sectors. Combining existing data onU.S. MNCs with the Japanese data, we illustrate the pattern and determinant of their foreignaffiliate sales by destination market across countries and industries for the period 1989-2005.Among our results, Japanese and U.S. MNCs are similar in the substantial growth of theirforeign affiliate sales and the importance of sales to local markets. However, Japanese MNCsare distinctive from U.S. MNCs in that Japanese affiliate sales in Asia were prominentlyhigher in host markets with lower educational attainment

International Intrafirm Transfer of Management Technology by Japanese Multinational Corporations

Authors analyze the pattern of intrafirm transfer of management technology from Japanese multinational corporations (MNCs) to their overseas affiliates by using firm-level micro data and discern the determinants of the extent of technology transfer achieved. Defining intrafirm transfer of technology achieved as the case where responsibility of the task such as top management, sales, and labor management is given to local staff rather than Japanese staff, authors found that top management has been transferred at a limited number of affiliates, while the task of labor management has been transferred at many affiliates. Among the affiliates in different regions, technology transfer has been relatively more extensively achieved at affiliates in Europe, while it has been relatively limited at affiliates in ASEAN countries. An examination of the determinants of technology transfer revealed that the length of operation of the affiliates, and the quality of labor in the host countries have significantly positive impacts for the affiliates in Asia. These observations indicate the importance of providing an FDI friendly environment, under which MNCs are likely to stay for a long period, and the importance of improving the quality of human resources through education and training, in order to promote intrafirm transfer of management technology.

Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS

Dual Programmed Cell Death Pathways Induced by p53 Transactivation Overcome Resistance to Oncolytic Adenovirus in Human Osteosarcoma Cells

Tumor suppressor p53 is a multifunctional transcription factor that regulates diverse cell fates, including apoptosis and autophagy in tumor biology. p53 overexpression enhances the antitumor activity of oncolytic adenoviruses; however, the molecular mechanism of this occurrence remains unclear. We previously developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301, that kills human osteosarcoma cells, but some human osteosarcoma cells were OBP-301-resistant. In this study, we investigated the antitumor activity of a p53-expressing oncolytic adenovirus, OBP-702, and the molecular mechanism of the p53-mediated cell death pathway in OBP-301-resistant human osteosarcoma cells. The cytopathic activity of OBP-702 was examined in OBP-301-sensitive (U2OS and HOS) and OBP-301-resistant (SaOS-2 and MNNG/HOS) human osteosarcoma cells. The molecular mechanism in the OBP-702-mediated induction of two cell death pathways, apoptosis and autophagy, was investigated in OBP-301-resistant osteosarcoma cells. The antitumor effect of OBP-702 was further assessed using an orthotopic OBP-301-resistant MNNG/HOS osteosarcoma xenograft tumor model. OBP-702 suppressed the viability of OBP-301-sensitive and -resistant osteosarcoma cells more efficiently than OBP-301 or a replication-deficient p53-expressing adenovirus (Ad-p53). OBP-702 induced more profound apoptosis and autophagy when compared with OBP-301 or Ad-p53. E1A-mediated miR-93/106b upregulation induced p21 suppression, leading to p53-mediated apoptosis and autophagy in OBP-702-infected cells. p53 overexpression enhanced adenovirus-mediated autophagy through activation of damage-regulated autophagy modulator (DRAM). Moreover, OBP-702 suppressed tumor growth in an orthotopic OBP-301-resistant MNNG/HOS xenograft tumor model. These results suggest that OBP-702-mediated p53 transactivation is a promising antitumor strategy to induce dual apoptotic and autophagic cell death pathways via regulation of miRNA and DRAM in human osteosarcoma cells. Mol Cancer Ther; 12(3); 314-25

Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas

骨・軟部肉腫は, 一部に治療抵抗性で予後の悪い症例が存在するため, 新たな治療法の確立が重要な課題である.　我々は, 5型アデノウイルスを基本骨格として, テロメラーゼ活性に依存して増殖する腫瘍融解ウイルス（OBP-301）や, coxsackie and adenovirus receptor（CAR）陰性の腫瘍細胞に感染するファイバー改変型ウイルス（OBP-405）を用い, 骨・軟部肉腫細胞に対する抗腫瘍効果を検討した.　 　14種類の骨・軟部肉腫細胞株に対してOBP-301の細胞障害活性を検討し, 12種類の細胞株でOBP-301に感受性を認めた.　また, OBP-301の細胞障害活性はCARの発現と相関していた.　さらに, テロメラーゼ活性の低い細胞に対しても, 5型アデノウイルスの複製に必須のE1Aによりテロメラーゼ活性の増強効果がおこり, 強い抗腫瘍活性を示すことを明らかにした.　次に, 骨肉腫脛骨同所性移植動物モデルを作成しOBP-301を投与したところ, OBP-301投与群では対象群と比べて有意に腫瘍増殖を抑制した.　最後に, OBP-301に感受性を認めなかったCAR陰性細胞株に対してOBP-405を用いて検討し, OBP-405が有効に作用することを確認した.　 　OBP-301やOBP-405を用いたウイルス療法は, 骨・軟部肉腫に対する新たな治療法となる可能性がある.

EXCHANGE RATE VOLATILITY AND MNCs' PRODUCTION AND DISTRIBUTION NETWORKS: THE CASE OF JAPANESE MANUFACTURING MNCs

This paper empirically examines the impacts of exchange rate volatility on the location choice by Japanese multinational corporations (MNCs) and their intra-firm trade. We use affiliate-level data for Japanese MNCs for 1995, 1998 and 2001. We found that high exchange rate volatility discourages the establishment of an affiliate by MNCs. Moreover, the high exchange rate volatility causes the shift from inter-firm to intra-firm transactions. These findings imply the importance of maintaining a stable exchange rate environment in order for MNCs to expand their production and distribution networks.Exchange rate volatility, location choice, intra-firm trade

Reconsidering the Backward Vertical Linkages of Foreign Affiliates: Evidence from Japanese Multinationals

Summary This paper examines the determinants of the backward vertical linkages of Japanese foreign affiliates in manufacturing for the period 1994-2000, focusing on the local backward linkages, or local procurement in the host country. Our major findings are twofold. First, the unobserved affiliate-specific characteristics explain the large part of the variation of the backward linkages among foreign affiliates. Second, the experience of the affiliate has positive and sometimes nonlinear effects on local procurement for the affiliates, especially in Southeast Asia and China.