Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense construct) tissue factor. In vitro, there was no difference in plating efficiency or growth between these cell lines.In vivo, tumor cells transfected to overexpress tissue factor grew more rapidly, and established larger and more vascularized tumors than control transfectants. Antisense transfectants grew the slowest and were the least vascularized. Anticoagulation of mice with warfarin did not alter the difference between these tumor lines. Tumor cells overexpressing tissue factor released more (compared with control transfectants) mitogenic activity for endothelial cells in parallel with enhanced transcription of vascular permeability factor/vascular endothelial cell growth factor (VEGF/ VPF), and diminished transcription of thrombospondin (TSP2), a molecule with anti-angiogenic properties. Antisense tissue factor transfectants, while releasing the lowest amount of mitogenic activity, had increased thrombospondin and decreased VEGF/VPF transcription compared with control transfectants or wild-type cells. Experiments with these sense, antisense, truncated sense, or vector tumor lines gave comparable results in complete medium, serum free medium or in the presence of hirudin, indicating that the activation of the coagulation mechanism was not likely to be responsible for changes in tumor cell properties. These results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism. (J. Clin. Invest. 1994. 94:1320-1327

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Thrombomodulin (TM), recognized as an essential vessel wall cofactor of the antithrombotic mechanism, is also expressed by a wide range of tumor cells. Tumor cell lines subcloned from four patients with malignant melanoma displayed a negative correlation between TM expression and cell proliferation in vitro and in vivo. Overexpression of wild-type TM decreased cell proliferation in vitro and tumor growth in vivo. TM mutants with altered protein C activation capacity lead to a similar effect. In contrast, transfection of melanoma cells with mutant TM constructs, in which a portion of the cytoplasmic or lectin domain was deleted, abrogated the antiproliferative effect associated with overexpression of wild-type TM. Experiments performed with either peptide agonists/antagonists of the thrombin receptor, with hirudin, or with inhibitors of thrombin-TM interaction did not alter the growth inhibitory effect of TM overexpression. These data suggest that TM exerts an effect on cell proliferation independent of thrombin and the thrombin receptor, possibly related to the binding of novel ligands to determinants in the lectin domain which might trigger signal transduction pathways dependent on the cytoplasmic domain.

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Context ‘Happy River’ is a new goal of river management in the new era of China. Aims To quantitatively evaluate the status of ‘Happy River’. Methods The evaluation model of ‘Happy River Index’ was established in this study through the analytic hierarchy process according to the three levels of ‘objective–criterion–index’. The criterion layer includes the following five parts (including weights): water protection (0.25), ecological construction (0.22), landscape aesthetics (0.20), water culture (0.18) and social functions (0.15); three to six indicators are set under each criterion layer as the index layer. On the basis of this, the main rivers in six regions of Shaoxing City were evaluated and the scores calculated comprehensively. Key results The results showed that the total scores of Shangyu District, Yuecheng District and Xinchang County were 89, 87 and 85 respectively, indicating that the rivers are in a very good state; the total scores of Zhuji City, Shengzhou City and Keqiao District were 82, 80 and 75 respectively, indicating that the state of rivers is relatively poor compared to the first three regions. Conclusions The follow-up work can be promoted from the aspects of ecological construction, water culture construction, water protection and social functions. Implications The established model and empirical study have provided a theoretical basis and data basis for the comprehensive evaluation of modern rivers.