Basic and clinical studies regarding to the identification of inflammatory factors promoting the malignant transformation mechanism in digestive organ cancer

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To investigate the cancer transformation of human hepatocellular carcinoma (HCC), the change of HMGB1 and its receptor TLR-4 with tissue macrophage (TAM) were analyzed. Moreover, the usefulness of FrB immunotoxin against TAM was studied if it could diminish tumor's malignant transformation. In HCC, correlations of HMGB1 level and number of TAM, and the number of TAM and patients prognosis were seen. For the knowledge about EMT, transcription factor ZEB-1 participated, too. On the other hand, after giving FrB immunotoxin to nude mouse HepG2 transplant model under skin, a clear effect of tumor promotion was seen. With these considerations, it was suggested that HMGB1 and derived TAM would contribute to the malignant transformation of HCCs, and FrB immunotoxin could be a treatment strategy.