| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Background : Patients with lung cancer are currently treated with a combination of several anti-cancer drugs. However, the occurrence of resistance to chemotherapy generally limits its efficacy in clinical practice. Thus, the mechanism by which resistance to chemotherapy develops is presently the focus of many investigations. So far,-we have demonstrated that the coagulation system plays important role in the pathogenesis of several lung diseases. For example, we have reported that the circulating level of tissue factor is significantly correlated with survival and clinical stage, of patients with lung cancer, and that it is closely associated with the malignant potential of lung cancer
Aim : In the present investigation we focused on the intracellular pathway associated with tissue factor expression in lung cancer, and evaluated the relationship between the inhibition of apoptosis and resistance to chemotherapy. In addition, we have also assessed the expression, of the inhibitor of fib
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rinolysis, thrombin-activatable fibrinolysis inhibitor
Method : In the experiments, we used highly sensitive lung cancer cell lines (PC/9. PC7/P, PC14/P, H69/P) and those with high resistance to anticancer drug (PC9/CDDP, PC7/CDDP, PC 14/CDDP, H69/CDDP). The expression of tissue factor and thrombin-activatable fibrinolysis inhibitor was evaluated by enzyme-linked immunoassay and reverse transcriptase polymerase chain reaction
Results : Lung cancer cell lines with resistance to anticancer drugs showed increased expression of tissue factor compared to sensitive cell lines. By contrast, cell lines with resistance to chemotherapy showed lower expression of thrombin-activatable fibrinolysis inhibitor than those with high sensitivity to cytotoxic drugs. In addition, the intracellular apoptotic pathway was inhibited in resistant lung cancer cells but not in sensitive cells
Conclusion : These results suggest that both tissue factor,and thrombin-activatable fibrinolysis inhibitor are involved in the mechanism of resistance to chemotherapy in lung cancer. Tissue factor and thrombin-activatable fibrinolysis inhibitor may constitute potential indicator of resistance to chemotherapy in patients with lung cancer Less
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