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)

To characterize the role of serum soluble interleukin-2 receptor (sIL-2R) in hepatitis C virus (HCV) infection, the level of sIL-2R was measured by ELISA in 117 subjects with chronic HCV infection and in 23 healthy controls. HCV RNA was detected by polymerase chain reaction in all subjects with HCV infection. Forty-seven patients with chronic hepatitis and 10 with liver cirrhosis were treated for six months with natural interferon-alpha. The sIL-2R levels of 40 asymptomatic HCV carriers (632 +/- 340 units/ml), 47 patients with chronic hepatitis (547 +/- 204 units/ml), 10 with cirrhosis (679 +/- 239 units/ml, and 20 with hepatocellular carcinoma (1145 +/- 487 units/ml) were significantly higher than those of healthy controls (380 +/- 191 units/ml) (P < 0.05, respectively). The levels of sIL-2R increased, as did the histological activity index scores (r = 0.348, P < 0.01). The level of sIL-2R rose after the initial administration of interferon in all 57 patients. In patients whom HCV RNA was eliminated from the sera within a six-month follow-up after cessation of treatment, the level of sIL-2R reverted to basal values, but in patients in whom HCV RNA was not eliminated the value was significantly higher than that before treatment. These results suggest that monitoring serum sIL-2R in patients with chronic HCV infection treated with interferon may provide information concerning the possibility of the elimination of HCV RNA.
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PMID:Serum levels of soluble interleukin-2 receptors and effects of interferon-alpha for patients with chronic hepatitis C virus. 764 88

Hepatitis B virus (HBV) infection in children is worldwide in distribution, but the features of HBV-associated liver disease differ depending on the route of transmission and the time of acquisition of the infection. The degree of liver injury varies from a mild disease to the development of cirrhosis and hepatocellular carcinoma, and depends on the replicative status of the viral genome. It is believed that the immune function plays a key role in the severity of HBV disease, and the impact of HBV mutants needs to be assessed. The goals of antiviral therapy in children are therefore, the clearance of viremia and HBV sequences from infected tissues, together with an improvement in the liver disease. Administration of 10 MU/m2 b.s. 3 times weekly over 6 months resulted in a significantly higher clearance of viremia, with normalization of ALT values and greater improvement in liver histology in treated than in untreated patients. Long-term follow-up of these cases reveals the presence of the viral genome in serum and liver by PCR without clearance of HBsAg. Complete eradication of HBV might need more years of evolution as for adult patients. The combination of more than one antiviral agent, as well as the potentiation of the immune system, needs to be assessed to improve the actual response rate obtained with interferon-alpha.
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PMID:Chronic hepatitis B in children. Natural history and treatment. 768 64

Chronic viral hepatitis caused by hepatitis B, C or D may lead to cirrhosis, hepatocellular failure and hepatocellular carcinoma. The morbidity of these diseases has necessitated a prolonged search for effective therapy. Interferon-alpha has been studied widely, and remains the mainstay of treatment. Therapy for hepatitis B has now become possible with the demonstration that alpha-interferons inhibit hepatitis B virus (HBV) replication and that prolonged therapy can lead to a remission in disease. A number of other cytokines, including thymosin, are being evaluated. Currently used nucleoside analogues and anti-retroviral therapies used in human immunodeficiency virus infection have not proven useful in chronic hepatitis B. There are a number of new experimental nucleoside analogues with activity against HBV. Unfortunately, fialuridine has been associated with severe mitochondrial damage and hepatotoxicity. Other stereoisomers may be more active and less toxic, but the potential danger of these drugs indicates that large scale clinical trials should proceed cautiously. Experimental test systems for the preliminary investigation of antiviral compounds in hepatitis B and C will be required. Antisense oligodeoxyribonucleotides may inhibit the expression of the HBV genes. The natural history of hepatitis C is uncertain. Therapeutic trials of interferon-alpha indicated that a proportion of patients may respond to treatment with this agent. There is most information about 3 mU t.i.w. administered for 6 months. It is not yet clear whether this dose is optimal. Multivariate analysis of several pretreatment parameters indicate that patients without cirrhosis are more responsive to interferon. The influence of genotypes of hepatitis C is the subject of considerable interest at present. Patients with diverse circulating quasispecies may be less responsive to therapy than those with a single major species. Improved responses have been observed in patients with lower levels of circulating hepatitis C virus RNA.
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PMID:Treatment and prevention of chronic viral hepatitis. 771 82

Single-agent activity for anthracyclines reflected by response rates of 10%-30% has been reported in patients with advanced hepatocellular carcinoma (HCC). Preclinical data indicate that alpha-interferon could enhance the cytotoxic activity of the anthracycline Adriamycin or its analog epirubicin. In a phase I/II study, 31 patients with biopsy-proven inoperable HCC were treated with interferon-alpha 2b given s.c. at a dose of 3 x 10(6) units/m2 per day for 5 days per week plus weekly epirubicin given at 25 mg/m2 as an i.v. bolus. The protocol called for 4 consecutive weeks of treatment followed by 1 week off treatment. In all, 15 patients had been previously treated; 6 patients had failed hormonal therapy (tamoxifen), 5 patients had failed prior anthracycline treatment, and 4 patients had received chemoembolization of the tumor and had subsequently progressed. A total of 30 patients were evaluable for response. In all, 1 patient (3%) achieved a partial response for 8+ months and 11 patients (35%) achieved stabilization of disease. Six patients had a fall in alphafetoprotein (AFP) values of > 50% during therapy. The median survival for all patients was 9.5 months (range, 3-34+ months). The main side effects were hematological toxicity and fever, both of which were considered tolerable. As an indicator of the immunostimulatory effects of interferon, an elevation in serum markers of inflammation [C-reactive protein (CRP), beta 2-microglobulin] was found in 15%-20% of patients. All patients had measurable Mx protein production during therapy, but these effects were not correlated to the clinical response. The clinical response rate achieved in this trial indicates that the combination of interferon and epirubicin, at least when used on the schedule reported herein, is not superior to treatment with either agent alone for patients with advanced HCC. However, single patients achieved a prolonged progression-free interval (8-10+ months) on this therapy, and it may therefore be an option for patients who have failed prior hormonal or single-agent anthracycline therapy.
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PMID:No synergistic activity of epirubicin and interferon-alpha 2b in the treatment of hepatocellular carcinoma. 782 77

Chronic infection with the hepatitis B virus is a major health problem worldwide. The only established therapy is interferon-alpha, with an efficacy of only 30-40% in highly selected patients. Nucleoside analogues do not show a significant clinical benefit. Molecular therapeutic strategies aimed at blocking gene expression include antisense DNA/RNA and ribozymes acting at the posttranscriptional level and triple helix formation blocking at the transcriptional level. In vitro, antisense oligodeoxynucleotides inhibit viral replication and gene expression in human hepatoma cell lines. In vivo, an antisense oligodeoxynucleotide directed against the 5'-region of the pre-S gene of the duck hepatitis B virus inhibited viral replication and gene expression in ducks. In vitro, ribozymes accurately cleave HBV substrate RNA. Triple helix formation is another very promising molecular approach. Results in hepadnaviral infection are not yet available, however.
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PMID:Molecular therapeutic strategies in hepatitis B virus infection. 786 75

We assessed the pattern of hepatitis C viremia in chronic liver disease by studying 100 hepatitis C virus antibody-positive patients: 48 with chronic hepatitis, 21 with cirrhosis and 31 with hepatocellular carcinoma and cirrhosis. Serum hepatitis C virus RNA was detected by means of both the conventional nested polymerase chain reaction and a newly developed assay based on branched DNA that can also quantify viremia. Hepatitis C virus RNA was found in 94 of 100 patients with polymerase chain reaction and in 71 of 100 patients with branched-DNA (p < 0.001). Mean viremia level (x 10(3) genome equivalents/ml +/- S.D.), as assessed with the branched-DNA test, was 5,700 +/- 7,618 in the 48 patients with chronic hepatitis, 3,340 +/- 3,633 in the 21 patients with cirrhosis and 1,768 +/- 2,770 in the 31 patients with hepatocellular carcinoma (p < 0.02). We also analyzed retrospectively the relationship between viremia and treatment. Fifty-five patients (41 chronic hepatitis, 14 cirrhosis) underwent interferon-alpha treatment. Mean viremia level was comparable among the 30 responders (5,644 +/- 8,207) and the 25 nonresponders (5,519 +/- 6,208) to interferon, but it was significantly lower (1,841 +/- 1,864) in the 12 of 30 responders (11 chronic hepatitis, 1 cirrhosis) who maintained remission up to 1 yr after cessation of interferon treatment. Fourteen patients (7 chronic hepatitis, 7 cirrhosis) with autoantibodies (12 antinuclear, 2 anti-liver-kidney microsomal) were treated with prednisone. The mean viremia level significantly increased after 3 mo of treatment, even in face of ALT decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatitis C viremia in chronic liver disease: relationship to interferon-alpha or corticosteroid treatment. 829 85

To evaluate the clinical efficacy of interferon-alpha in hepatocellular carcinoma, 71 adult Chinese patients with histologically proven inoperable hepatocellular carcinoma were randomized to receive recombinant interferon-alpha 2a (50 x 10(6) IU/m2) intramuscularly three times a week (n = 35) or no antitumor therapy (n = 36). The survival of interferon-alpha-treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.0471); median lengths of survival were 14.5 and 7.5 wk, respectively. Objective tumor regression greater than 50% was observed in 31.4% (11 of 35) of patients receiving interferon-alpha. Interferon-alpha induced tumor regression greater than 50% in 11 (31.4%) patients. Compared with the group receiving no antitumor therapy, the interferon-alpha therapy group had more tumor regression (p < 0.0001) and less tumor progression (p = 0.001). This high-dose interferon-alpha therapy was relatively well tolerated; only 34.3% of patients required reduction of dosage by one third or one half because of persistent fatigue. Two patients with diabetes mellitus (one also had tabes dorsalis) exhibited mental deterioration that might have been partially attributable to interferon-alpha therapy. We conclude that interferon-alpha is useful in a proportion of Chinese patients with inoperable hepatocellular carcinoma, both in prolonging survival and in inducing tumor regression.
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PMID:Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. 838 88

We investigated whether regulation of interferon-alpha gene expression could be involved in liver tumor biology and the role, if any, of hepatitis B virus in the regulation of tumor cytokine gene expression. Gene expression was investigated at the transcriptional level using 'in situ' hybridization of cytokine message with an interferon-alpha cDNA probe and at the translational level with immunohistochemistry using an immunoperoxidase technique. Compared to histologically normal liver, a greater percentage of tumor and non-tumor-involved liver tissue sections (67-80% vs. 17%) contained cells positive for interferon-alpha messenger RNA, many of which were also seen to contain an increased number of transcripts (> 100 grains/cell). Hepatitis B infection did not appear to play a role in gene activation, at the hepatocellular level, in liver disease. Except for sinusoidal cells, cells containing cytokine transcripts also produced mature immunoreactive protein. Absence of interferon-alpha protein within mononuclear and sinusoidal cells in seronegative hepatocellular carcinoma tissue with/without underlying liver disease suggested deficient cytokine gene expression, at the post transcriptional level, within these cells in this group. Bile duct epithelia in tumor tissue were found to contain immunoreactive protein for interferon-alpha. In summary our results suggest that interferon-alpha gene activation in hepatocellular carcinoma occurs as a result of the liver cell damage and does not play a dominant role in tumor biology.
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PMID:Gene expression regulation for interferon-alpha in hepatocellular carcinoma. 839 Oct 40

Human recombinant interferon-alpha (IFN-alpha) was assayed for its antiviral effect on hepatitis A virus (HAV) replication in the human hepatoma cell line PLC/PRF/5. IFN-alpha resulted in concentration-dependent reduction of HAV antigen expression and HAV replication. IFN-alpha had a prophylactic effect, but was still effective when it was added after the infection, even at the end of the first replication cycle. An important increase in 2',5'-oligoadenylate synthetase activity in the IFN-treated human liver cells was observed. The antiviral effect of IFN-alpha could be attributed to the induction of this enzyme. Moreover we have shown that IFN-alpha and glycyrrhizin were synergistic in their antiviral actions against HAV. IFN-alpha emerged, from the present study, as a promising candidate for chemotherapy of severe forms of hepatitis A.
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PMID:Antiviral activity of recombinant interferon-alpha on hepatitis A virus replication in human liver cells. 858 61

The viral load of hepatitis C virus, as reflected by hepatitis C virus viremia, has been shown to have important clinical implications. In this study the hepatitis C virus core protein level in serum was evaluated for the detection and quantification of hepatitis C virus viremia. Hepatitis C virus core protein in serum was detected using a simple and sensitive fluorescent enzyme immunoassay. Hepatitis C virus core protein was quantitated in 100 healthy subjects, 258 patients with hepatitis C virus infection and 108 patients with non-hepatitis-C-virus-related chronic liver diseases. HCV-RNA was determined using the branched DNA (bDNA) assay and reverse-transcription polymerase chain reaction. The detection limit of this fluorescent enzyme immunoassay was found between 10(4) - 10(5) copies/ml HCV-RNA equivalent. There was a good correlation between the core protein and bDNA assay results (p <0.01). Hepatitis C virus core protein was detected in 81% of patients with hepatitis C virus infection (acute hepatitis 4/5, chronic hepatitis 85/104, cirrhosis 64/73 and hepatocellular carcinoma 56/76) but in none of the healthy subjects and patients with non-hepatitis C virus chronic liver diseases. The amount of hepatitis C virus core protein in patients with hepatitis-C-virus-related hepatocellular carcinoma was lower compared to chronic hepatitis and cirrhosis (p <0.05). All 26 patients treated with interferon-alpha showed parallel changes between HCV-RNA and core protein levels. This fluorescent enzyme immunoassay is simple and quick (assay time <3 h) with sensitivity at least matching the bDNA assay. Similar levels of hepatitis C virus core protein were detected in patients with chronic hepatitis and cirrhosis, but patients with hepatocellular carcinoma tended to have a lower level of hepatitis C virus core protein.
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PMID:Simple fluorescent enzyme immunoassay for detection and quantification of hepatitis C viremia. 875 Jan 76


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