Relationship between cellular ATP content and cellular functions of primary cultured rat hepatocytes in hypoxia.

The importance of oxygen in maintaining the functional integrity of hepatocytes has been well established in a variety of experimental models, such as in vivo, perfused liver and isolated hepatocytes. However, one of the shortcomings of these systems is their short life span. Therefore, we have examined the effects of long-term hypoxia on cellular adenine nucleotide content and cellular functions, such as albumin production, urea production and DNA synthesis, in adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density of 11 x 10(4) and 5 x 10(4) cells/0.18 mL per cm2 for the study of albumin and urea production and DNA synthesis, respectively, at various oxygen tensions (20, 12, 8 and 5%) for 24 h. Cellular ATP content in cultured hepatocytes in hypoxia gradually declined, corresponding to the decrease in oxygen tension, and the cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen. Albumin production also decreased in parallel with the decrease in cellular ATP content in cultured hepatocytes in hypoxia. However, even when cellular ATP content gradually declined corresponding with the decrease in oxygen tension in cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production remained at a high level; in contrast, DNA synthesis was completely suppressed. These results suggest that the cellular ATP content decreases in cultured hepatocytes during long-term hypoxia in relation to oxygen tension and that the relationship between decreased ATP levels and liver function in cultured hepatocytes during hypoxia differs for albumin production, urea production and DNA synthesis.

[A case of hepatocellular carcinoma responding to intraarterial infusion of epirubicin and mitomycin C].

A 64-year-old male was admitted for treatment of hepatocellular carcinoma. He was diagnosed as having many tumors in the area of S6 and the AFP level was elevated to 878 ng/ml. Initially, intraarterial infusion of Epirubicin only was not effective. After the first course of treatment, tumors increased in size and the AFP level was elevated. Next, intraarterial infusion of Epirubicin and Mitomycin C was performed. After the second course of treatment, the AFP level decreased from 5,006 ng/ml to 754 ng/ml and the tumors had almost completely disappeared on angiography. The tumors continued to decrease in size and thereafter the AFP level decreased to 10 ng/ml and was not elevated. The tumors almost completely disappeared in this case, and the coadministration of Epirubicin and Mitomycin C provided effective.

[Therapy of hepatocellular carcinoma with UFT--clinical evaluation of its effect in the combination therapy with transcatheter arterial embolization or one shot therapy].

In 55 hepatocellular carcinoma patients treated with transcatheter arterial embolization or one shot therapy, the prognosis of patients treated with UFT (group A; n = 23) were historically compared with those of patients treated without UFT (group B; n=32). In group A, survival rate was 91.3% at 6 month; 67.5% at 1-year, 24.3% at 2-year, 24.3% at 3 year, in group B, 59.4% at 6-month, 37.5% at 1 year, 16.1% at 2-year. In these comparison, group A revealed significantly higher survival rate than group B. These results indicated that UFT was effective as maintenance therapy after transcatheter arterial embolization or one shot therapy with hepatocellular carcinoma.