Embryonic stem (ES) cells may differentiate along a hepatocyte lineage; however, currently there are no reports of culture conditions yielding high levels of hepatocyte-specific gene expression in these cells. We investigated culture conditions for differentiating ES cells into hepatocyte-like cells in vitro. Various combinations of culture media, growth and differentiation factors, and substratum precoatings were evaluated, and it was determined that a combination of Iscove's modified Dulbecco's medium with 20% fetal bovine serum, human insulin, dexamethasone. and collagen type I precoating was optimal for directing mouse ES cells along a hepatocyte lineage. Treatment of mouse ES cell with the optimal condition led to prealbumin gene expression 20% as high, and albumin synthesis 7% as high, as in mouse liver. The optimal culture condition also induced albumin gene expression in differentiated human ES cells 1% as high as in normal human hepatocytes as shown by Western blot analysis, and cells were positive for human albumin by immunocytochemistry. In addition, our optimal condition led to high levels of albumin gene expression in primary mouse hepatocytes after 35 days of culture, levels 10-fold higher than with other hepatocyte differentiation media. In conclusion, our optimal condition directed both mouse and human ES cells along a hepatocyte lineage. This represents the initial step in establishing cell lines that can be employed in cell-based therapeutics in humans and for toxicology and pharmacology studies.

BACKGROUNDThe therapeutic efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is limited by the small volume of coagulation necrosis obtained at each activation of the RF system and the sometimes irregular burn shape due to the proximity of large vessels that have a cooling effect. To improve the efficacy of RFA, the authors designed RFA with balloon occlusion of the hepatic artery (balloon‐occluded RFA). In this study, we investigated the efficacy of balloon‐occluded RFA and compared the coagulation diameters obtained with balloon‐occluded RFA and standard RFA.METHODSWe retrospectively studied 31 patients with 42 HCC lesions measuring less than 4 cm in the greatest dimension. We performed balloon‐occluded RFA for 12 patients (n = 15 nodules) and standard RFA for 19 patients (n = 27 nodules). Initial therapeutic efficacy was evaluated with dynamic computed tomography scan performed 2 weeks after one treatment.RESULTSThere were no significant differences in the ablation conditions such as the frequency of a fully expanded electrode, the number of needle insertions, application cycles, or treatment times between the two groups. However, the greatest dimension of the area coagulated by balloon‐occluded RFA was significantly larger (greatest long‐axis dimension, 36.6 ± 3.8 mm; greatest short‐axis dimension, 30.1 ± 6.0 mm; n = 15 lesions) than that coagulated by standard RFA (greatest long‐axis dimension, 26.7 ± 6.4 mm; greatest short‐axis dimension, 23.1 ± 5.0 mm; n = 27 lesions; greatest long‐axis dimension, P < 0.001; greatest short‐axis dimension, P < 0.001).CONCLUSIONSBalloon‐occluded RFA is superior to standard RFA for the treatment of many hepatocellular lesions, especially when larger volumes of coagulation are required. Cancer 2002;95:2353–60. © 2002 American Cancer Society.DOI 10.1002/cncr.10966

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BACKGROUNDBiologic characteristics of tumors are greatly affected by genetic aberrations. However, to the authors' knowledge there is no study that shows that cytogenetic information is useful for estimating prognosis of patients with hepatocellular carcinoma (HCC).METHODSComparative genomic hybridization (CGH) analysis was performed in 41 HCCs to examine whether the analysis of cytogenetic aberrations allows us to estimate biologic behavior of HCC.RESULTSTumor recurrence was linked to the loss at 13q (P = 0.0027) and to the number of DNA copy number aberrations (DCNAs; P = 0.0003). The decrease in DNA copy number at 8p and 13q and amplification at 11q13 were significantly associated with unfavorable outcome of patients (P = 0.017, P = 0.012, and P = 0.00081, respectively). The number of DCNAs was significantly different between favorable and poor prognosis patients with HCC; 5.78 ± 2.7 versus 11.13 ± 4.8 (P = 0.004), and it was an independent prognostic marker in HCCs.CONCLUSIONSThe current study indicates that cytogenetic information provided by CGH is useful for estimating prognosis of patients with HCC. Cancer 2002;94:746–51. © 2002 American Cancer Society.DOI 10.1002/cncr.10254