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The new multifunctional antitumor conjugates containing ascorbic acid and 5-fluorouracil (5-FU) were synthesized from bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, ascorbic acid and/or a chain spacer, followed by condensation with 5-FU. The synthesized conjugates were identified by 1 H and 13 C NMR spectroscopies and elemental analysis. The in vitro cytotoxicities of these conjugates were determined and their antitumor activity was evaluated. The IC 50 values (drug concentration for 50% inhibition of tumor growth) indicated that the synthesized conjugates were better inhibitors against cancer cells and were lower in cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined against mice bearing the sarcoma 180 tumor cells. The life spans (T/C) of mice treated with the conjugates were higher than for the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity, based on the embryo chorioallantoic membrane assay.

Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterized by the presence of arteriovenous malformation (AVM) in multiple organs. HHT is caused by mutations in genes encoding major constituents for transforming growth factor-β (TGF-β) family signaling: endoglin (ENG), activin receptor-like kinase 1 (ALK1), and SMAD4. The identity of physiological ligands for this ENG-ALK1 signaling pertinent to AVM formation has yet to be clearly determined. To investigate whether bone morphogenetic protein 9 (BMP9), BMP10, or both are physiological ligands of ENG-ALK1 signaling involved in arteriovenous network formation, we generated a novel Bmp10 conditional knockout mouse strain. We examined whether global Bmp10-inducible knockout (iKO) mice develop AVMs at neonatal and adult stages in comparison with control, Bmp9-KO, and Bmp9/10-double KO (dKO) mice. Bmp10-iKO and Bmp9/10-dKO mice showed AVMs in developing retina, postnatal brain, and adult wounded skin, while Bmp9-KO did not display any noticeable vascular defects. Bmp10 deficiency resulted in increased proliferation and size of endothelial cells in AVM vessels. The impaired neurovascular integrity in the brain and retina of Bmp10-iKO and Bmp9/10-dKO mice was detected. Bmp9/10-dKO mice exhibited the lethality and vascular malformation similar to Bmp10-iKO mice, but their phenotypes were more pronounced. Administration of BMP10 protein, but not BMP9 protein, prevented retinal AVM in Bmp9/10-dKO and endothelial-specific Eng-iKO mice. These data indicate that BMP10 is indispensable for the development of a proper arteriovenous network, whereas BMP9 has limited compensatory functions for the loss of BMP10. We suggest that BMP10 is the most relevant physiological ligand of the ENG-ALK1 signaling pathway pertinent to HHT pathogenesis.

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Today the concept of corporate social responsibility has become an essential element for coexistence of corporations and the society. In this study the impact of four responsibilities of business organizations proposed by Archie Carroll (economic, legal, ethical, and discretionary) on customer loyalty through the mediating effect of trust and company-consumer identification is analyzed. A questionnaire survey was conducted for four well-known Korean companies (Dong Suh Food, LG Household and Health Care, Samsung Electronics, and Hyundai Motor). After factor analysis, legal and ethical responsibilities were grouped as the same factor, thus three social responsibilities were finally used for hypotheses testing. Major findings were as follows：First, economic responsibilities had positive impact on honesty trust, professionalism trust, favorableness trust, and company-consumer identification, Second, legal/ethical responsibilities were found to have significant effects on honesty trust, favorableness trust, and company-consumer identification. Third, in the case of discretionary responsibilities, professionalism trust, favorableness trust, and company-consumer identification were revealed to have a significant positive relationship. Fourth, only two trust variables (honesty and professionalism) and company-consumer identification had positive influence on the loyalty of customers. These findings are expected to help decision makers to set up corporate objectives and choose action items for corporate social responsibility. At the last part, implications of the study and future research directions were discussed.