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)

Chronic hepatitis may take the form of a hepatitis B infection, a delta virus infection, or a non-A, non-B hepatitis including hepatitis C. All the viruses involved are transmitted predominantly by parenteral or sexual routes. New insights into the structure of the hepatitis B virus (HBV) and the immune response mechanisms of the organism permit a clear definition of the replicative state of the virus, and allow predictions to be made about the outcome of the disease. Development of cirrhosis and hepatocellular carcinoma are the major complications associated with impaired life expectancy. Recently, the hepatitis C virus (HCV) was identified as the agent responsible for most cases of chronic non-A, non-B hepatitis. The development of an assay for the detection of HCV-antibodies facilitated the diagnosis of this type of hepatitis. Moreover, the use of screening tests for hepatitis B and hepatitis C in blood donors will decrease the risk of acquiring hepatitis via contaminated blood products. Treatment of chronic hepatitis B and C with alpha-interferon has shown promising results. However, the dosage schedule, the period of treatment, and the selection of patients needs to be evaluated in further studies.
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PMID:Epidemiology, clinical course and treatment of chronic viral hepatitis. 185 Nov 29

The paper presents the results of experimental and clinical studies on the antitumor effect of larifan. A statistically significant inhibition of growth of some continuous mouse tumors by larifan in a dose of 2.5 mg/kg given for 5-6 days and by a combination of larifan with an immunomodulator, inosiplex, tested on hepatoma XXIIa which has a rather low sensitivity to larifan. The antitumor effect of larifan may be due to interferon production and immunomodulating effect. Treatment with 0.05% larifan ointment of patients with cervical dysplasia of moderate degree resulted in a significant increase of previously diminished production of alpha-interferon after 10-14 vaginal tampons and clinical cure in 88% of cases. A course of 8-10-day larifan monotherapy given before radial therapy resulted in a considerable improvement in patients with cervical cancer of II-III stages, and subsequently, for 1 1/2-month combined radial therapy, no significant changes in production of alpha-IF were observed. At the same time, in patients with cervical cancer treated by radial therapy alone a significant decrease of alpha-IF production by blood mononuclears was observed by the end of therapy.
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PMID:[The experimental and clinical antitumor action of the interferon inducer larifan]. 190 72

Non-A, non-B hepatitis is the most common serious complication of blood transfusion and also occurs in a sporadic form whose routes of transmission are currently unknown. While generally mild in its acute presentation, non-A, non-B hepatitis frequently progresses to chronic hepatitis which may eventuate in cirrhosis and hepatocellular carcinoma. The disease is caused by a small, enveloped RNA virus now designated hepatitis C virus, which has similarities to the flaviviruses. Studies using the recently developed antibody assay have indicated that hepatitis C virus is the predominant agent of both transfusion-associated and sporadic non-A, non-B hepatitis. In 50-85% of transfusion-associated cases, a donor can be found who is positive for antibodies to the hepatitis C virus. Current data indicate that these antibodies are present in approx. 0.5% of blood donors in the United States and Europe, 1.5% in Japan and 6% in Africa, as well as in 60-80% of haemophiliacs and intravenous drug abusers and approx. 20% of dialysis patients. With changes in donor selection and transfusion practices, the incidence of transfusion-associated non-A, non-B hepatitis has declined from rates of 5-10% prior to 1985 to estimated current rates of 2-4%. The introduction of the anti-HCV test should effect an additional 50% reduction in transfusion-associated non-A, non-B hepatitis. In addition to these preventive measures, effective therapy now appears at hand in the form of alpha-interferon. The efficacy of other antiviral agents and the potential for combination therapies also need to be explored.
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PMID:Clinical, virological and epidemiological basis for the treatment of chronic non-A, non-B hepatitis. 196 64

Novel immunotherapeutic strategies for combating colon cancer are also being explored in pancreatic, hepatic, and esophageal cancers. Preliminary clinical trials in patients with pancreatic cancer suggest a therapeutic role for anti-idiotypic antibodies against tumor-specific monoclonal antibodies (MoAbs)--eg, CO17-1A, BW 494/32--but not for MoAbs when used alone. Adding low doses of interferon gamma to CO17-1A enhances in vitro antibody-dependent cellular cytotoxicity against pancreatic tumor cells; CO17-1A plus a regimen of 5-FU/doxorubicin/mitomycin has resulted in beneficial therapeutic effect. Treatments with immunotoxins, radiolabeled MoAbs, and adoptive immunotherapy are still being tested preclinically. In 105 patients with unresectable hepatocellular cancer, a 7% complete and 41% partial regression rate with 131I-labeled antiferritin has been reported. In several patients, radiolabeled antiferritin caused sufficient shrinkage of lesions to permit curative resection. Pretreatment with low-dose doxorubicin may improve the efficacy of low-dose radiolabeled antiferritin antibody therapy. Chemoembolization of primary hepatocellular carcinoma, based on the concept of regional therapy for metastatic colorectal cancer, has shown considerable palliative and survival benefit in patients with unresectable disease. Although adoptive immunotherapy has been used to treat hepatocellular carcinoma, the results have been disappointing. The development of immunotherapeutic approaches to esophageal cancer is less advanced than that for other gastrointestinal malignancies. Paralleling the successful use of 5-FU/interferon alfa-2a in colon cancer are two phase II studies that have evaluated this combination in patients with locally advanced esophageal cancer. The objective response rate (27%) was encouraging.
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PMID:Implications of current therapeutic approaches in colorectal cancer for other gastrointestinal malignancies. 199 29

Alpha-interferon has emerged as the most effective agent for the treatment of chronic hepatitis when active replication of virus B, C, or D is present. Exogenous administration of human alpha-interferon, now possible through modern large-scale production methods, is associated with suppression of virus in blood. Amelioration of liver disease occurs in 35% of patients with hepatitis B virus and in 50% with hepatitis C virus with interferon doses of 30 and 10 MU per week, respectively, for 16-26 weeks; after therapy, persistent normalization of serum alanine aminotransferase is observed in 35% and 27%, respectively. Similar results have now also been reported for chronic hepatitis D. Enhanced response rates (greater than 50%) may be obtained by prolonged intermittent interferon therapy. Combination of interferon with another 'antiviral' agent (vidarabine, acyclovir, prednisone) has not increased therapeutic efficacy. Alpha-interferon induces side effects such as fatigue, flu-like syndrome, myalgia, and changes in mood and granulocytes. Patients with decompensated cirrhosis are particularly prone to bacterial infection and disease exacerbation and should receive lower doses. Interferon, when applied skillfully, induces the highly beneficial transition of active viral replication into viral latency, thereby greatly reducing infectivity, symptoms, and activity of the liver disease. Prevention of death from liver failure or hepatocellular carcinoma is to be expected.
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PMID:Treatment of chronic viral hepatitis anno 1990. 212 46

Non-A, non-B (type C) hepatitis is a serious world problem which typically results in chronic hepatitis and may lead to cirrhosis and hepatocellular carcinoma. alpha-Interferon has recently been studied in a number of randomized controlled trials throughout the world. The results of those studies are reviewed here. ALT levels were normalized by 2-3 MU recombinant interferon alfa-2b, three times per week s.c. for 6 months (p less than 0.001 vs. control) in 36% of patients in five trials. Biopsy tests also demonstrated histological improvement in lobular and periportal inflammation. Unfortunately, relapse is a common problem in these studies, occurring in 49% of patients treated with 3 million units and 57% of those treated with 1 million units. Retreatment usually brings remission once again. In the future, long-term studies will further elucidate the natural history of the disease and documented guidelines for interferon dosage and duration of dosing in a wider range of patient subgroups will become available.
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PMID:Recombinant alpha-interferon treatment of non-A, and non-B (type C) hepatitis: review of studies and recommendations for treatment. 212 92

Of all the hepatotropic viruses, HBV is associated with the greatest worldwide morbidity and mortality. This is because of the ease of transmission and the potential for progression to a chronic infective carrier state, with the complications of cirrhosis and hepatocellular carcinoma. The use of PCR has shown that some of the earlier concepts concerning the interpretation of serological data were inaccurate. Many patients with anti-HBe and anti-HBs have viral DNA detectable by PCR, and some hepatocellular carcinoma patients have detectable HBV DNA in their livers in the absence of all serological markers of HBV disease. The clearance of HBV infected cells from the liver is dependent on the interplay between the interferon system and the cellular limb of the host immune response. The importance of the nucleocapsid proteins as targets for sensitized cytotoxic T cells has been established for chronic HBV infection. The importance of pre-S sequences as inducers and targets of the virus-neutralizing humoral immune response is becoming established, but their precise role must await the development of in vitro models of hepadnavirus infection and a greater understanding of the mechanisms of viral uptake. The epidemiology and clinical course of the disease can be modified by immunization, immune stimulation and antiviral chemotherapy. For the developing world, a programme of immunization at birth would be the most effective way of eliminating this disease, but at present the cost is prohibitive. For the developed world, immunization is realistic for the at-risk population, and anti-viral and immunostimulatory therapy available for those already infected. In adult acquired chronic HBV infection alpha-interferon produces HBe antigen clearance in 40-60% of cases and is followed by resolution of the hepatic inflammation. Results in neonatally acquired infection are less impressive and prednisolone priming followed by interferon may be needed. The presence of a mutation in the pre-core region of some virus isolates has recently been described. Hepatocytes infected with this virus cannot produce HBe antigen and the course of the liver disease is fairly rapid. Whether this mutant causes liver damage in the same way as the wild virus or is directly cytopathic remains unclear, and its relationship to fulminant hepatitis is under investigation.
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PMID:The hepatitis B virus. 214 22

C1 inhibitor (C1inh), a member of the serine protease inhibitor gene superfamily, is a glycosylated plasma protein inhibiting the proteolytic activities of C1r and C1s and involved in the regulation of coagulation, fibrinolysis and kinin-releasing systems. In this study, the in vitro effect of androgen hormones, dehydroepiandrosterone (DHEA), testosterone (TEST) and recombinant human gamma-interferon (gamma-IFN), has been determined on the production of C1inh in human cell lines. In both human monocytoid/histiocytoid cell line U937 and in hepatoma derived cell line HepG2, DHEA and TEST upregulated the gene expression and secretion of C1inh. The most pronounced effect was detected in the concn range 10(-7)-10(-9) M of the hormones. Under the same conditions DHEA and TEST had no detectable effect on the biosynthesis of C3, C2 and factor B by these cells, but DHEA at higher concn (10(-4) M) slightly increased that of C4 in HepG2 cells. Both in U937 and in HepG2 cells recombinant gamma-IFN markedly increased the gene expression and secretion of C1inh. This effect of gamma-IFN was abolished by histamine.
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PMID:Hormonal regulation of complement biosynthesis in human cell lines--I. Androgens and gamma-interferon stimulate the biosynthesis and gene expression of C1 inhibitor in human cell lines U937 and HepG2. 215 44

The mRNAs of transiently expressed cytokine genes contain AUUUA-rich sequences in the 3' untranslated regions. In order to examine whether the AU-specific endoribonuclease V (EC 3.1.27.8) described previously by us transinactivates those mRNA species, we introduced a 51-nucleotide ATTTA sequence from tumor necrosis factor into the 3' untranslated region of beta-globin gene. Transcripts of that construct, synthesized in vitro, were prone to endoribonuclease V digestion at those AU-rich sequences. Stimulation of human macrophages with lipopolysaccharide resulted in a shift of the association state of the enzyme from the nuclear matrix-associated to the free form. This shift was strongly prevented by the hepatitis B surface antigen (HBsAg) and more weakly by hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region. HBsAg and, to a lesser extent, hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region inhibited the release of alpha interferon, tumor necrosis factor alpha, and granulocyte-macrophage colony stimulating factor, while it had no effect on interleukin-1 production from stimulated macrophages. Using the human hepatoma cell line PLC/PRF/5, we provide further experimental evidence that endoribonuclease V acts in trans as a posttranscriptional inactivator for nuclear matrix-associated cytokine transcripts. These results suggest that those cytokine transcripts which contain reiterated (overlapping) AUUUA sequences are degraded by nuclear matrix-associated endoribonuclease V. This degradation was comparably high in cells incubated with HBsAg or cells which produced this antigen.
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PMID:Immunosuppressive function of hepatitis B antigens in vitro: role of endoribonuclease V as one potential trans inactivator for cytokines in macrophages and human hepatoma cells. 215 63

The major cause of chronic post-transfusion hepatitis, the hepatitis C virus (HCV), has been identified. HCV is a single-stranded linear RNA virus with characteristics similar to the flaviviruses. A different agent, the hepatitis E virus, is associated with epidemic (enterically-transmitted) non-A, non-B hepatitis. At present, infection with HCV is recognized by the finding of anti-HCV antibodies, positive in up to 90% of patients with chronic non-A, non-B post-transfusion hepatitis. Antibodies to HCV are detected in 1% of normal volunteer blood donors and in the majority of donors implicated in post-transfusion hepatitis. HCV antibodies are also found in patients with autoimmune liver disease and hepatocellular carcinoma. Moreover, HCV infection may contribute to the pathogenesis of liver disease in alcoholic patients. The role of HCV infection in fulminant non-A, non-B hepatitis and hepatitis-associated aplastic anemia has not been elucidated as yet. Therapy of chronic non-A, non-B hepatitis with recombinant human alpha-interferon has been shown to improve or normalize aminotransferase levels in approximately 50% of patients, most of whom have evidence of HCV infection. However, relapse after cessation of treatment is common. In the future, screening blood for evidence of HCV infection may prevent most cases of non-A, non-B post-transfusion hepatitis.
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PMID:Hepatitis C. 215 11


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