Development of molecular- targeting therapy and prediction of mode of recurrence by analysis of molecular mechanism of invasion and metastasis of hepatocellular carcinoma

点击翻译按钮获取中文摘要

1) Based on the previous studies, we focused on DNA binding protein A (dbpA) to investigate the candidate gene for occurrence and development of HCC. By the analyses of immunostaining of 82 resected specimen of HCC we clarified that dbpA was closely related to the portal invasion, venous invasion, differentiation grade of cancer cell and serum level of α fetoprotein, and further showed that transformation of T to G in the promoter region may be associated with poor prognosis. These findings suggested that dbpA might be not only a biomarker for invasion of HCC, but also a candidate gene of molecular-targeting therapy.2) Based on the previous studies showing that angiopoietin-2 is an important angiogenic factor in HCC, we studied the mechanism on the induction of this molecule. Consequently, we found that PGE2 and COX-2 is strong inducers for angiopoietin-2, and that COX-2 inhibitor suppressed the tumor growth in vivo through inhibiting the tumor angiogenesis. We also suggested that angiopoietin-2 and its receptor Tie-2 may be candidate molecules for targeting therapy.3) We found that not only VEGF but also anaerobic glycolysis- related enzyme of hexisokinase-II was enhanced under the hypoxic environment in HCC, suggesting the limitation of antiangiogenic therapy.