The incidence of hepatocellular carcinoma was lower in patients with sustained response to interferon therapy than historical controls and nonresponders. Interferon therapy may decrease the risk for hepatocellular carcinoma in patients with chronic hepatitis C.

Summary Chemotherapy is not effective for hepatocellular carcinoma (HCC). HMG-CoA redutase inhibitors have cytostatic activity for cancer cells, but their clinical usefulness is unknown. To investigate whether pravastatin, a potent HMG-CoA reductase inhibitor, prolongs survival in patients with advanced HCC, this randomized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital. 91 consecutive patients <71 years old (mean age 62) with unresectable HCC were enroled in this study. 8 patients were withdrawn because of progressive liver dysfunction; 83 patients were randomized to standard treatment with or without pravastatin. All patients underwent transcatheter arterial embolization (TAE) followed by oral 5-FU 200 mg -1 d for 2 months. Patients were then randomly assigned to control (n = 42) and pravastatin (n = 41) groups. Pravastatin was administered at a daily dose of 40 mg. The effect of pravastatin on tumour growth was assessed by ultrasonography. Primary endpoint was death due to progression of HCC. The duration of pravastatin administration was 16.5 ± 9.8 months (mean ± SD). No patients in either group were lost to follow-up. Median survival was 18 months in the pravastatin group versus 9 months in controls (P = 0.006). The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival. Pravastatin prolonged the survival of patients with advanced HCC, suggesting its value for adjuvant treatment.

Liver cirrhosis is characterized by the hyper-accumulation Liver fibrosis/cirrhosis is characterized by hyper-accumulaof connective tissue components in the liver and is often tion of fibrous tissue components and is commonly observed accompanied by hypo-albuminemia, ascites, and esophageal in later or terminal states of chronic hepatic diseases. In ongovarices. In a prolonged stage, severe hepatic failure, or hepaing work, we found that the administration of human recombitocellular carcinoma, can occur. Chronic hepatic injuries nant hepatocyte growth factor (hrHGF) suppressed the onset caused by drugs, chemicals, alcohol abuse, or viral infections of liver fibrosis/cirrhosis in several distinct models and accelare predominant pathogenic causes for cirrhosis. Although erated the recovery from liver fibrosis/cirrhosis in rats. Rethe pathogenic mechanisms of cirrhosis are not fully underpeated administration of porcine serum for 10 weeks to rats stood, the over-production of extracellular matrices in the induced liver fibrosis without any accompanying hepatocelluliver, as well as of chronic parenchymal hepatocellular injury, lar injuries; in addition, the intravenous (i.v.) administration are likely to initiate the onset of cirrhosis. Therefore, preferof hepatocyte growth factor (HGF) to these rats suppressed ential hepatocellular replication and cytoprotection against increases in fibrous components and hydroxyproline contents hepatic injuries, as well as the stimulation of degradation in the liver, thus preventing the onset of liver fibrosis. Reand remodeling of extracellular fibrous components, seems peated administration of dimethylnitrosamine (DMN) for four to inhibit the onset or progress of hepatic fibrosis/cirrhosis. weeks induced liver cirrhosis, as characterized by the hyperSeveral lines of studies have shown that hepatocyte growth accumulation of fibrous components, infiltration of mononufactor (HGF), originally purified as a potent mitogen for rat clear leukocytes, and hepatic dysfunction. When HGF was hepatocytes, 1-3 is the long-sought hepatotrophic factor for injected daily for four weeks along with DMN-treatment, the liver regeneration. [4][5][6][7] Following the onset of various types of onset of DMN-induced hepatic fibrosis/cirrhosis was suphepatic injuries, HGF messenger RNA expression is rapidly pressed; the numbers of infiltrating mononuclear cells, fibrous tissue components, and hydroxyproline content in the liver up-regulated in the livers of experimental animals. 8,9 Serum were decreased. When HGF was injected for two weeks fol-HGF levels are elevated in patients with various hepatic dislowing four weeks of DMN-treatment, HGF accelerated the orders. 10,11 Extensive in vivo studies on the efficacy of recomrecovery from liver cirrhosis and prevented death due to he-binant HGF on hepatic regeneration revealed that HGF elicits patic dysfunction. Likewise, HGF-injection suppressed the on-a potent hepatotrophic action. HGF strongly stimulates DNA set of liver fibrosis, when liver fibrosis had be...

Background and aims: The genetic contribution to inflammatory bowel disease (IBD) is under investigation. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and IBD. We investigated the association between an intercellular adhesion molecule 1 gene (ICAM-1) polymorphism located on chromosome 19p13 and IBD in a Japanese population. Methods: We compared 207 Japanese patients who had IBD (79 with Crohn's disease (CD); 128 with ulcerative colitis (UC)) with 103 unrelated Japanese controls. We determined R241G and K469E polymorphisms of the ICAM-1 gene using polymerase chain reaction (PCR) techniques. Results: Both frequency and carriage rate of the K469 allele were significantly higher in IBD patients than in controls (allelic frequency, p c =0.0026; carriage rate, p c =0.0034; odds ratio 2.59; 95% confidence interval 1.42-4.68). Furthermore, the frequency of the K469 allele was significantly increased in both CD and UC. Subgroup analysis demonstrated that both K469 allelic frequency and K469 carriage rate were significantly higher in patients with the small bowel and colon type of CD and entire colitis compared with healthy controls. Conclusions: We identified an overall association between IBD and ICAM-1 K469 in a Japanese population. Further studies of this chromosome region are required to elucidate the gene responsible for IBD.

So far, treatment with anti-cancer agents has failed to achieve satisfactory results in hepatocellular carcinoma. In the process of hepatocarcinogenesis, ras has been shown to play a role. ras requires a farnesyl moiety for activation. It has been found that UCFI-C (manumycin), an antibiotic, inhibits farnesyl protein transferase, an enzyme that catalyzes farnesylation. Therefore, we investigated the effects of UCFI-C on cell growth, prenylation of cellular proteins including ras and Rapl, MAP kinase activity, activities of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and synthesis of cholesterol in a ras-activated human hepatoma cell line, Hep G2. Treatment with varying concentrations of UCF1-C(10-30 microM for 24 and 72 hr resulted in a time- and dose-dependent inhibition of cell numbers. 3H-Thymidine incorporation was also inhibited in a dose-dependent manner, with 50% inhibition after 44 hr being observed at a concentration of 17 microM. UCFI-C dose-dependently inhibited ras farnesylation and MAP kinase activity, but did not decrease Rap 1++ geranylgeranylation or prenylation of 21-to 26-kDa proteins. Neither the activities of 3-hydroxy-3-methylglutaryl-coenzyme A reductase nor cholesterol synthesis were inhibited. These results suggest that UCFI-C antagonizes the growth of Hep G2 via the suppression of ras farnesylation and could be a lead for the development of new anti-cancer agents blocking the function of oncogenic ras associated with human cancer, including hepatocellular carcinoma.