Conclusion: In conclusion, caspase 8 and survivin may contribute an important regulatory mechanism for tumor cell proliferation and apoptosis, and may be prognostic predictors in HCC. injection was recently reported to be effective against HCC with PVI, though the therapy is not always applicable for the patients with arterial abnormality. Therefore we tried combination therapy of transcatheter arterial cisplatin embolization and radiation, and will report the effectiveness and toxicity of the therapy. Methods: The combined therapy was conducted in 7 HCC patients with PVI. Transcatheter arterial embolization with 1mg/kg cisplatin powder (IA call) was performed against intralobar lesions, followed by external radiation targeted for PVI (60Gy in 2 Gy fractions). The following variables were evaluated with the survival rate: gender, age, viral etiology, Child's class, performance status, and location of PVI. Results: One (16%) patient showed complete response and another two (33%) partial response. Two (33%) showed no change, and one (16%) showed progress of disease. The survival rates at six months among overall patients were 85.7%. Adverse events were limited to nausea and appetite loss. One of the patients with partial response underwent curative resection, and is still alive without any recurrence for 530 days. Conclusions: The combination therapy of cisplatin embolization and radiation is safe, effective and also feasible to the patients with arterial abnormality. This therapy is suggested to be a useful alternative therapy for the patients with extensive PVI. Recently, the injection port has been used for hepatic arterial infusion chemotherapy (HAI) in Japan. HAI is usually used for the treatment of multifocal bilobar tumors of the liver or HCCs combined with portal vein tumor thrombosis (PVTT), not amenable to TACE. This study examined the efficacy and toxicity of repeated hepatic HAI using lipiodol suspension mixed with cisplatin powder. Methods: From April 2005 to September 2008, 20 patients with inoperable advanced HCC were enrolled in this study. All received cisplatin powder (50mg) and Lipiodol (2ml) suspension, with an intervening 4 weeks interval. The drugs were delivered from an injection port. 13 patients had HCC with PVTT, and 7 had HCC without PVTT. 11 patients with liver function of Child grade A, 7 of grade B, and 2 of grade C were enrolled. Result: The mean number of HAI given during the follow-up period was 4.1 times. We found complete response in 1 case, partial responses in 6, no change in 6, and progressive disease in 7. The overall response rate was 35.0%. The 1-year survival rate was 36.7% and the 2-year survival rate was 12.1%. Although 3 patients had cisplatin-induced anaphylaxis, no severe adverse events (hepatic failure and renal failure) were observed. Conclusion: Chemo-lipiodolization using cisplatin powder delivered via an injection port provides some clinical benefits without severe adverse events in patients with far advanced HCC. Background: Recently, the antitumor efficacy of angiogenesis inhibitors is expected in the treatment to hepatocellular carcinoma. The gene expression relevant to the vascularization, which is a target of these inhibitors, has a difference according to each case and it is thought that it influences the therapeutic effect of them. However, there are still few reports of mRNA expression of Vascular Endothelial Growth Factor (VEGF) receptors in HCC. Methods: The relative mRNA level of VEGF and its receptors (KDR and flt-1) was analyzed using quantitative RT-PCR in 51 patients with HCC. Matched samples of HCC (T) and non-tumor liver tissue (NT) were obtained by fine needle (21gauge) biopsy. Results: Gene expression level of VEGF and flt-1 was significantly higher in HCC than NT (VEGF; p<0.001, flt-1; p<0.001). According to the clinicopathological findings, gene expression level of VEGF and KDR in HCC was significantly high in hypervascular HCC compared to hypovascular HCC (VEGF; p=0.002, KDR; p=0.042). Additionally, flt-1 tended to be expressed higher in hypervascular HCC than hypovascular HCC (p=0.09). Moreover, gene expression level of VEGF, KDR and flt-1 tended to be higher in advanced-stage HCC than early-stage HCC. Conclusion: Not only VEGF but KDR and flt-1 were highly expressed in hypervascular and advanced HCC. Aims: Fibrinogen-like protein 2/fibroleukin (fgl2) has been reported to play a vital role in the pathogenesis in MHV-3 (mouse hepatitis virus) induced fulminant and severe hepatitis, spontaneous abortion, allo-and xeno-graft rejection by mediating "immune coagulation". Fgl2 functions as an immune coagulant with the ability to cleave prothrombin to thrombin directly. Therefore, this study was designed to examine the role of fgl2 in tumor development. Methods: Tumor tissues from 133 patients with six types of distinct cancers and the animal tumor tissues from human hepatocellular carcinoma (HCC) model on nude mice (established from high metastasis HCC cell line MHCC97LM6) were obtained. Results: Hfgl2 was detected in tumor tissues from 127 out of 133 patients as well as tumor tissues collected from human HCC nude mice. Hfgl2 was highly expressed both in cancer cells and interstitial inflammatory cells including macrophages, NK cells, and CD8 + T lymphocytes and vascular endothelial cells. Hfgl2 mRNA was localized in cells that expressed hfgl2 protein. Fibrin (nogen) co-localization with hfgl2 expression was determined by dual immunohistochemical staining. In vitro, IL-2 and IFN-increased hfgl2 mRNA by 10-100 folds and protein expression in both THP-1 and HUVEC cell lines. One-stage clotting assays demonstrated THP-1 and HUVEC cells expressing hfgl2 had increased procoagulant activity following cytokines stimulation. Conclusion: The hfg12 contributes to the hypercoagulability in cancer and may induce tumor angiogenesis and metastasis via cytokine induction. . The therapy was either terminated at the end of the first cycle in cases with progressive disease, or continued for at least 2 cycles, when responses to treatment were evaluated by Eastern Cooperative Oncology Group criteria. Results: Of 146 patients treated (male, 79%; median age, 64 years), 64% had Child-Pugh A, and 31% had B. 90% had either metastasis or vascular invasion. 71% had metastasis and 49% had vascular invasion. On the basis of independent assessment, three (2.1%) patients achieved a complete response, thirteen (8.9%) had a partial response, and 42 (28.8%) had stable disease. There was no grade 3/4 drug related toxicities. Median overall survival was 6.9 months. Conclusion: Combination therapy of IFN +5-FU has modest efficacy in HCC. Background: AMT is a mixture of approved pharmaceuticals in low therapeutic doses (human insulin and chlorpheniramine) and herbal components (aqueous camomile extract). Preclinical and phase I data in healthy volunteers showed a favourable safety profile for AMT. This pilot study should examine efficacy and safety of AMT in the patients with advanced hepatocellular carcinoma (HCC). Methods: Thirteen patients with advanced HCC (TNM stage III-IV), who did not respond to existing therapy, were treated with i.m. AMT at 0.066 ml/kg up to a maximum volume of 5 ml twice daily for 1-10 months. Primary study objectives: Clinical Benefit Response (CBR). Secondary objectives: safety of AMT, tumor response according to WHO-RECIST criteria, quality of life (QOL) and iimmunomodulatory effects. The effects were evaluated by cytokine production of PBMCs before and after the treatment. Results: There were no significant safety issues. Four and 3 patients showed positive and stable responses for CBR, respectively. Tumor response was 1 PR, 6 SD and 6 PD. Even in the patients with PD, 2 and 1 patients showed positive and stable responses for CBR. QOL data showed clear improvement.