Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Here, we will briefly review current and evolving therapies for chronic hepatitis C. Standard therapy with (pegylated) interferon-alpha and ribavirin achieves sustained response rates of up to about 40% in genotype 1- and about 80% in genotype 2- and 3-infected patients. Recent progress in the molecular virology and pathogenesis of hepatitis C has allowed the identification of novel antiviral targets and therapeutic strategies. These will likely complement existing therapeutic modalities in the near future.
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PMID:[Therapy of hepatitis C]. 1209 32

Chronic hepatitis B virus (HBV) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Its prevalence approaches 10% in hyper endemic areas. The aim of treating chronic HBV infection is to halt progression of liver injury by suppressing viral replication or eliminating infection. This study was planned to evaluate the advantages of combination therapy with interferon-alpha plus second-generation nucleoside analogues (lamivudine or famciclovir), or vaccination with a pre-S2 and S proteins containing vaccine in chronic HBV infection. 29 patients were divided into three groups and were treated with the following combinations: (1) IFN-alpha2a 9 million units 3x week for 6 months with HBV vaccine 20 microg given on 0, 1 and 2 months; (2) IFN-alpha2a 6 million units 3x week plus famciclovir 250 mg 3x day for 6 months; (3) IFN-alpha2a 6 million units 3x week plus lamivudine 100 mg/day for 6 months. Complete response was suspected in 3 patients in group 1, in 4 patients in group 2, and in 7 patients in group 3. Partial response was suspected in 4, 1 and 2 patients in groups 1, 2 and 3, respectively. The results of the present study suggest that the combination of IFN-alpha with lamivudine is more effective than the combination of IFN-alpha with HBV vaccination or famciclovir.
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PMID:Comparison of different treatment combinations for chronic hepatitis B infection. 1212 Aug 84

We have studied the antiviral activities of five recombinant interferon-alpha (IFN-alpha) subtypes, namely IFN-alpha1, -alpha2, -alpha5, -alpha8 and -alpha10, in eight human liver cancer cell lines. The relative antiviral activities, expressed in terms of the mean 50% inhibitory concentration (IC50), were different for each cell line. In general, IFN-alpha8 was the most potent, IFN-alpha2, -alpha5, and -alpha10 were intermediately active, and IFN-alpha1 was the least potent in the all cell lines. The observed differences between the IC50s of IFN-alpha1 and -alpha8 ranged from 250- to 2200-fold in these cell lines. Thus, the ranking order of relative antiviral activity was similar but the sensitivity to the subtypes was different among these cell lines. The relative antiviral activities of the subtypes were associated with the induction of 2',5'-oligoadenylate synthetase (2',5'-OAS) in the typical hepatocellular carcinoma cell line HAK-3 but not in the cell line KYN-3. Next, we examined for synergistic antiviral activity induced by IFN-alpha2 and -alpha8 that has been reported for the hepatocellular carcinoma cell line, HepG2. Synergism was observed in three of the eight liver cell lines at an IFN-alpha2 to -alpha8 ratio of 60:40, and is considered to reflect the synergistic induction of 2',5'-OAS.
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PMID:Different antiviral activities of IFN-alpha subtypes in human liver cell lines: synergism between IFN-alpha2 and IFN-alpha8. 1227 Jul 38

Infection with hepatitis B and/or hepatitis C virus is strongly associated with hepatocellular carcinoma (HCC). HCC likely develops through a sequence of chronic inflammation to fibrosis to cirrhosis and, eventually, dysplasia. Medical therapies aimed at the prevention of HCC are predicated on the interruption of this sequence by means of antiviral therapy. In this review, the authors summarize the available experience with prophylactic medical therapies and a number of questions that remain unanswered. Overall, although it appears that interferon-alpha therapy is beneficial in the prevention of HCC in patients with viral hepatitis, more experience is required before definitive recommendations can be made.
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PMID:Role of antiviral therapy in the prevention of hepatocellular carcinoma. 1235 36

We report a case of recurrent hepatocellular carcinoma (HCC) successfully treated with a combination therapy of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU), which was administered intravenously. A 49-year-old Japanese man who underwent a right hepatectomy for HCC developed tumor recurrence in the liver 19 months after surgery. Abdominal CT revealed multiple metastatic lesions in the liver. He received a combination therapy of 500 mg/day of 5-FU that was given intravenously by continuous infusion and 5 x 10(6) units of IFN-alpha, given three times weekly. The treatment resulted in a fall in serum PIVKA-II (protein induced by vitamin K antagonism) levels from 337 mAU/ml to 65 mAU/ml and disappearance of tumor stain in enhanced CT. 5-FU is usually administered by arterial infusion in a combination therapy of IFN-alpha and 5-FU. However, 5-FU infusion may be possible intravenously in the combination therapy of IFN-alpha and 5-FU for the treatment of advanced HCC.
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PMID:[A case of recurrent hepatocellular carcinoma successfully treated with a combination therapy of interferon-alpha and intravenous continuous infusion of 5-fluorouracil]. 1240 33

Hepatitis C virus (HCV) is now the major cause of transfusion-associated and parenterally transmitted viral hepatitis and accounts for a significant proportion of hepatitis cases worldwide. The majority of infections become persistent and approximately 20% of chronically infected individuals develop cirrhosis, which is strongly associated with progression to hepatocellular carcinoma. Molecular biological investigations into the structure and function of HCV and its genes has led to the identification of a number of potential targets for selective antiviral intervention. The present review summarizes current research activity into these novel drug targets and addresses the basis for clinical non-response in the current interferon-alpha-based therapies. Future therapeutic strategies that utilize HCV-specific antiviral agents should prove effective in controlling active viral replication, but the risk of emergence of drug-resistance will need to be addressed due to the quasispecies feature of HCV replication.
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PMID:Mechanisms of drug resistance and novel approaches to therapy for chronic hepatitis C. 1247 63

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, induces apoptosis in a variety of cancer cells with little or no effect on normal cells. Human hepatoma cells, however, are resistant to TRAIL-induced apoptosis. Since interferon-alpha (IFN-alpha) is capable of enhancing TNF-alpha-induced apoptosis in certain cancer cells, we evaluated the effect of IFN-alpha on TRAIL-induced apoptosis of human hepatoma cells. IFN-alpha pretreatment enhanced TRAIL-induced apoptosis of HuH-7 and Hep3B cells, in which IFN-alpha upregulated the expression of DR5, a death receptor of TRAIL, and downregulated the expression of survivin, which has an antiapoptotic function. In contrast, IFN-alpha did not enhance TRAIL-induced apoptosis of HepG2 cells, in which expression of DR5 and survivin was not affected by IFN-alpha. On the other hand, TRAIL activated NF-kappa B composed of RelA-p50 heterodimer, a key transcription factor regulating cell survival, in HuH-7 and HepG2 cells. However, IFN-alpha pretreatment repressed the TRAIL-mediated activation of NF-kappaB and decreased its transcriptional activity in HuH-7 but not in HepG2 cells. Moreover, IFN-alpha pretreatment clearly augmented TRAIL-mediated caspase-8 activation in HuH-7 cells. Our results suggest that IFN-alpha could sensitize certain human hepatoma cells to TRAIL-induced apoptosis by stimulating its death signaling and by repressing the survival function in these cells.
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PMID:Interferon-alpha sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-kappa B inactivation. 1264 68

Patients chronically infected with hepatitis B virus (HBV) run the risk of developing cirrhosis and hepatocellular carcinoma in later life. Antiviral treatment offers the only means of preventing such an undesirable outcome. To date, interferon-alpha (IFN-alpha), an immunomodulator, and two synthetic nucleoside analogues, lamivudine and adefovir dipivoxil, are the only licensed antiviral agents for the treatment of chronic HBV infection. However, the standard treatment endpoints of loss of HBeAg with or without seroconversion to anti-HBe, normalization of serum transaminase levels, loss of HBV-DNA and improvement in liver histology following monotherapy with either types of agent are only achievable in approximately 20-30% of those treated. Long-term treatment with lamivudine is effective in suppressing viral replication, but drug-resistant mutants arise with increased length of treatment. Nevertheless, such mutants appear to be susceptible to adefovir and other nucleoside analogues that are undergoing Phase II/III clinical trials at the moment. Therapeutic vaccination and other molecular approaches such as antisense oligonucleotides, ribozymes, DNA vaccines, dominant-negative proteins and aptamers are possible future antiviral therapies, which will supplement our armamentarium against chronic HBV infection. It seems certain that combination therapies involving two or more nucleoside analogues, immunomodulators or gene therapies will be the future treatment regimens for chronic HBV infection.
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PMID:Hepatitis B virus: old, new and future approaches to antiviral treatment. 1265 50

The role of interferon-alpha (IFN-alpha) remains unclear in prevention of virus-induced hepatocellular carcinoma in humans. We have investigated it herewith in the X/myc transgenic mouse model of Hepadnavirus-related hepatocarcinogenesis because of upregulation of c-myc oncogene in the liver. We have demonstrated that IFN-alpha can downregulate dose-dependently hepatocyte proliferation and c-myc overexpression at early premalignant stages, while it does not affect either hepatocyte apoptosis or telomerase activity at these steps. However, continuous and long-term administration of IFN-alpha dose-dependently delays tumor onset in dysplastic livers and increases overall survival of animals, more efficiently whether started before the onset of dysplasia. The present study therefore highlights that early preventive administration of IFN-alpha can slow down evolution towards hepatocellular carcinoma via repression of c-myc and hepatocyte proliferation at premalignant steps in experimental c-myc-induced hepatocarcinogenesis. However, the transient effect observed in this study emphasizes a need to clarify the possible mechanisms of acquired resistance and subsequent therapeutic escape. Our experimental model may be a pertinent tool to explore antioncogenic properties of IFN-alpha in human cirrhotic livers showing c-myc upregulation.
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PMID:Long-term high-dose interferon-alpha therapy delays Hepadnavirus-related hepatocarcinogenesis in X/myc transgenic mice. 1274 99

The purpose of this pilot study was to evaluate the efficacy and adverse events of systemic combined chemotherapy with low dose of 5-fluorouracil (250 mg/m2, 5 days), cisplatin (10 mg/m2, 5 days), and interferon-alpha (2.5 million units, three times weekly) for advanced hepatocellular carcinoma (HCC) underlying liver cirrhosis. Six patients who had advanced HCC with tumor thrombi in the main portal trunk were enrolled in this study. Partial response was achieved in 2, stable disease in 1, and disease progressed in 3. Objective responses were achieved in 2 (33%), however, marked decreases of alpha-fetoprotein protein and protein-induced vitamin K antagonist or absence (PIVKAII) levels were also seen in one patient (stable disease). Four patients showed hematologic or renal toxicity, which were well tolerated and managed. Our systemic combined chemotherapy resulted in favorable response and was well tolerated in those with advanced HCC underlying liver cirrhosis, complicated by leukocytopenia and thromobocytopenia.
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PMID:Systemic combined chemotherapy with low dose of 5-fluorouracil, cisplatin, and interferon-alpha for advanced hepatocellular carcinoma: a pilot study. 1277 83


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