Naoyuki Kawahara

Enhanced Coexpression of Thioredoxin and High Mobility Group Protein 1 Genes in Human Hepatocellular Carcinoma and the Possible Association with Decreased Sensitivity to Cisplatin

Abstract Thioredoxin (TRX), a disulfide-reducing intracellular protein, functions as a cellular defense mechanism against oxidative stress. In this study, we asked whether expression of TRX , glutathione-thiol transferase π, and high mobility group protein 1 ( HMG-1 ) genes is enhanced in human hepatocellular carcinoma and whether expression of these genes is associated with sensitivity to cisplatin. Both TRX and HMG-1 were co-overexpressed in almost all cancerous lesions in comparison to normal tissue in surgically resected hepatocellular carcinomas of 20 patients. Tumor sensitivity to cisplatin [ cis -diamminedichloroplatinum (II)], but not to mitomycin C or doxorubicin, correlated with mRNA levels of TRX in cancer tissue. TRX and HMG-1 may be useful tumor markers, and TRX might be also a useful marker for sensitivity to cisplatin in human hepatocellular carcinomas.

Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma

Recurrence of small hepatocellular carcinoma (HCC) is common. Recent studies have suggested that the status of the underlying liver parenchyma is a significant risk factor for recurrence of HCC.

Clinicopathologic features and prognosis of resected hepatocellular carcinomas of varied sizes with special reference to proliferating cell nuclear antigen

Background. Proliferating cell nuclear antigen (PCNA) is an intranuclear protein that is linked closely to the cell cycle. An immunohistochemical study was performed on the expression of PCNA in various sized hepatocellular carcinomas (HCCs) to determine the relation between the proliferative activity of cancer cells and prognosis.

Surgical treatment strategy for patients with stage IV hepatocellular carcinoma

BACKGROUND This study was conducted to identify the prognostic indicators for patients with stage IV hepatocellular carcinoma (HCC), as well as to clarify the strategy of surgical treatment for those patients. METHODS Forty-six patients with stage IV HCC were included in this study. Prognostic factors were univariately and multivariately analyzed. Furthermore, the significance of intraoperative treatment for residual tumors was investigated in patients with an absolute noncurative operation. RESULTS The poor prognostic factors were as follows: host factors, Childs classification of B and C and immunosuppressive acidic protein level of greater than 400 micrograms/ml; tumor factors, tumor diameter of greater than 5 cm, poorly differentiated histologic features, positive portal vein invasion, and intrahepatic metastases involving more than three segments; others, an absolute noncurative operation and no preoperative treatment. Tumor diameter of more than 5 cm was then suggested to be an independent prognostic indicator. Survival of patients with stage IV-A HCC who underwent a curative operation was similar to that of those with stages III HCC: Furthermore, the survival of patients with Stage IV-A who had an absolute noncurative operation but underwent either intraoperative microwave coagulation or ethanol injection to the residual HCCs was not statistically different from that of those with a curative operation. CONCLUSIONS Therefore for stage IV-A HCC surgical treatment is considered to be both useful and the first choice of treatment when all the tumors in the liver can be removed or when the residual tumors can be treated during operation by either microwave coagulation or ethanol injection as a result of an incomplete removal of the tumors.

Angiogenesis as a new target for cancer treatment.

Abstract Neovascularization is often required for rapid growth of solid tumors and also limits vascular metastasis of tumor cells. Neovascularization-targeting agents are a recent innovation that may be a novel means of anticancer therapy. These antiangiogenic drugs have been developed by targeting cell proliferation of vascular endothelial cells, basement-membrane-degrading enzymes, angiogenic factors/receptors, extracellular matrix, angiogenesis signaling, and cell-cell/cell-matrix interactions. In this report, we describe how tumor angiogenesis occurs and how antiangiogenic agents are developed.