The labeling index of 8-OHdG had no correlation with Grading, Staging, fatty and iron deposit among all cases. Conclusions: There is possibility that oxidative stress might not associate with the carcinogenesis of HCC in some cases without hepatitis viral infection. Background: No effective chemopreventive agent has been approved against hepatocellular carcinoma (HCC) yet. Since neovascularization plays a pivotal role in HCC, an angiostatic agent is considered as one of the promising approaches. Recently, it has reported that vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) exert anti-angiogenic activity. The aim of the current study was to elucidate the combination effect of the clinically used VK and ACE-I on cumulative recurrence after curative treatment, especially in consideration of neovascularization. Methods: VK (menatetrenone; 45 mg/day) and/or ACE-I (perindopril; 4 mg/day) were administered for 36 to 48 months after the curative therapy for HCC. The cumulative recurrence and several indices were analyzed. Results: A 48-month follow-up revealed that the combination treatment with VK and ACE-I markedly inhibited the cumulative recurrence of HCC in association with suppression of the serum level of vascular endothelial growth factor (VEGF); a central angiogenic factor. The serum level of lectin-reactive a-fetoprotein was also suppressed almost in parallel with VEGF. These beneficial effects were not observed with single treatment of VK or ACE-I for 36 months. Conclusions: The combination treatment of VK and ACE-I may suppress the cumulative recurrence of HCC after the curative therapy, at least partly through suppression of the VEGF-mediated neovascularization. Aim: The aim of this study was to clarify the cilnicopathologic features and management of hepatocellular carcinoma (HCC) patients surviving more than 5 years after hepatectomy. Materials & Methods: Retrospective study was carried out on 823 HCC patients who underwent curative hepatectomy between 1973 and 2002. Clinicopathologic factors in 5-year survivors and patients who died within 5 years were compared. The prognostic factors affecting survival were examined among the 5-year survivors. Results: There were 290 patients who survived for more than 5 years after initial hepatectomy, and 83 of those patients survived for more than 5 years after HCC recurrence. The overall 3-, 5-, 10-and 20-year survival rates were 57.4%, 40.9%, 17.2%, and 8.5% respectively. In multivariate analysis, absence of underlying cirrhosis, solitary tumor, alfa-fetoprotein less than 1000 ng/mL, and absence of microscopic vascular invasion were favorable independent factors associated with 5-year survival. Negative hepatitis C virus antibody status was favorable independent factor associated with longer disease-free interval and survival after tumor recurrence. Multimodal treatments such as repeat hepatectomy or percutaneous ablation led to improved survival after recurrence, compared with the survival after transarterial chemoembolization (p<.05). Conclusions: The results suggest that patients without underlying cirrhosis who have a solitary HCC that does not demonstrate vascular invasion or high AFP levels might survive for longer than 5 years after the initial hepatectomy. Close follow-up and multimodal treatment could contribute to prolongation of survival in such patients, even if cancer recurrence occurs. The history of the use of carbon ion radiotherapy (CIRT) for treating hepatocellular carcinoma (HCC) goes back to 1995, when clinical trials were initiated at the National Institute of Radiological Sciences. We have already reported that CIRT used for the treatment of HCC is safe and effective, and that it causes only minor liver damage. In a phase II clinical trial, the local control and cumulative overall survival rates were 94 % and 35 % at 5 years, respectively. However, the patients with tumor adjacent to the gastrointestinal tract are thought to be ineligible for CIRT because of the high risk of radiation injury of the digestive organs. In order to extend the indication of CIRT, we have challenged the CIRT for such patients under the use of spacers. A case was a 67-year-old female with 8cm tumor in Segment 4. In radiological findings, the tumor revealed typical enhancement pattern for HCC, and was near the EC junction. She had been judged ineligible for hepatectomy because of the high retention rate of indocyanine green. She could undergo the 42.8 GyE/2-fraction CIRT after the placement of GORE-TEX Soft Tissue Patch under the laparoscopic procedure. Up to the present date, no adverse effect due to the spacer has been occurred, and an apparent anti-tumor effect has been observed. This method seems to have a promising efficacy for extension of the indication of CIRT to the patients with tumors adjacent to the gastrointestinal tract. Background: Previously we reported that high ubiquitination was marker of human hepatocellular carcinoma. On the basis of these finding, we firstly analyzed the effect of Bortezomib(proteasome inhibitor) on human HCC cell line. We also reported that HHM/DIP1/GCIP1 was early marker for human hepatocarcinogenesis. HHM was suggested to be a new tumor suppression gene, but the mechanism was not well confirmed. We analyzed change of HHM signal by Bortemib. Method and Result: We used HCC cell line (HuH7, HLF, HepG2) . The inhibitory effect of Bortezomib was evaluated using MTT assay. 20nM Bortezomib significantly inhibited proliferation of HCC cell line. The inhibitory effect by 20nM Bortezomib was similar with 10 M Cisplatin. On the other hand, Bortezomib has no inhibit effect in isolated hepatocyte from Rat. In this condition, we analyzed the expression of Cyclin D1, Phospho-Rb and HHM in HCC cell line by Western Blot analysis. Expression of Cyclin D1, Phospho-Rb decreased, but HHM was increased with time. Next we analyzed cell cycle by FACS. Bortezomib induced HCC cell line into cell cycle arrest in G2/M. The transcriptional activity of HHM was also activated by Bortezomib administration using pTimer-promoter-HHM plasmid. Conclusion: Bortezomib has specific anti-proliferative effect on hepatocellular carcinoma. The induction of HHM by Bortezomib might be related with cell cycle arrest. Bortezomib will be a useful drug for HCC.