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)

Interferon alpha is the only available therapy for patients with chronic hepatitis B. With interferon alpha 3-15 MU thrice weekly or 5 MU daily during 3-6 months one-third of the patients achieve seroconversion of HBeAg and HBV-DNA together with normalization of aminotransferases and slight improvement of histology. Loss of HBsAg is reported in a minority of responders during treatment, but increases during follow-up. Patients with baseline alanine aminotransferase of at least twice the upper limit of normal and low HBV-DNA concentration achieve the best response rates. HIV-positive patients with low CD4 counts and Asians are poor responders. As side-effects influenza-like symptoms are experienced by almost all patients. Mild leukopenia, thrombocytopenia and decreased hairgrowth are frequently reported. Severe depression, depersonalization and psychosis are reported in a small number of patients but tend to be poorly recognized in some studies. The decision whether dose reduction is indicated seems strongly related to the opinion of the investigator. Although long-term effects on the occurrence of cirrhosis and the development of hepatocellular carcinoma are not available yet, the achieved results are promising.
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PMID:Current status of interferon alpha in the treatment of chronic hepatitis B. 143 94

Adriamycin is one of the chemotherapeutic agent often administered in the treatment of unresectable hepatocellular carcinoma. On monotherapy, the reported rate response is between 0 to 15 p. cent, without improvement on survival. Its combination with other cytotoxic molecules, such as interferon, has been suggested to improve the percentage of response rates. We present the case of a 73 years old man, who underwent a prolonged partial response of a hepatocellular carcinoma with adriamycin and recombinant human interferon alpha-2.
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PMID:[Prolonged partial remission of a hepatocellular carcinoma treated with adriamycin and recombinant human alpha-2 interferon]. 166 Jun 87

Three viruses are responsible for posthepatitic cirrhosis: hepatitis B virus, hepatitis D (also called delta) virus and hepatitis C virus formerly known as non-A, non-B virus. Delta virus is a defective organism which can replicate only when coinfection with hepatitis B virus is present. These three viruses cause chronic active hepatitis which, after a period of 5 to 30 years, gives rise to posthepatitic cirrhosis. Chronic infections with these viruses account for more than 90 p. 100 of chronic active hepatitis in France and constitute a major cause of cirrhosis. Beside complications (hepatocellular insufficiency, portal hypertension, hepatocellular carcinoma) which are common to all types of cirrhosis irrespective of their origin, the course of posthepatitic cirrhosis is characterized by possible episodes of reactivation of chronic hepatitis and by a very high risk of hepatocellular carcinoma. Two kinds of treatment are now available: antiviral therapy (basically with interferon alpha) and liver transplantation. Antiviral therapy must, of course, be given before the stage of cirrhosis has been reached. Liver transplantation in these patients raises special problems due to recurrence of viral infection in the graft. Vaccination against hepatitis B virus, which also prevents the B-delta coinfection, must be systematic in populations at risk.
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PMID:[Post-hepatitis B, B-D and C cirrhosis]. 190 35

The natural history of chronic hepatitis B virus (HBV) infection in children may lead to hepatic cirrhosis and hepatoma. Since the antiviral effect of recombinant interferon alpha (rIFN-alpha) in the treatment of chronic hepatitis in adults has been proven, a controlled study of therapy using rIFN-alpha in children chronic hepatitis due to HBV has been carried out. Twenty-four children (4-14 years old) HBsAg, HBeAg and HBV-DNA positive were randomly allocated to one of three groups: 1) n = 8, control; II) n = 8, who received 10 MU/m2 of rIFN-alpha (Boehringer Ingelheim)/m2 body surface, I.M., twice a week for six months and III) n = 8, treated with 7.5 MU/m2 under the same conditions. No basal differences between the three groups were observed. No intolerable toxicity was observed and all children completed the treatment period. At the end of the therapy, 5 patients in groups I (1 case), II (2 cases) and III (2 cases), had lost circulating HBV-DNA. With respect to HBeAg, 3 patients (one from each group) were negative by the sixth month, developing anti-HBe. Decreases in ALT levels among rIFN-alpha responder patients were observed, while no changes occurred in the rest. A significant decrease in the percentage of HBcAg positive hepatocytes was detected only among treated patients, when comparing the basal and final liver biopsies. In summary, rIFN-alpha therapy in children is well tolerated. In addition, these results suggest that rIFN-alpha has an antiviral effect.
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PMID:[A controlled study of treatment with recombinant interferon alpha of chronic hepatitis due to the B virus in childhood]. 203 70

Soluble serum beta 2-microglobulin has been thought to result from membrane shedding by activated T-lymphocytes. This hypothesis could explain the increase of beta 2-microglobulin serum levels during virally induced mononucleosis, but not elevated levels as observed in other virally induced and in malignant diseases. In this paper we demonstrate that beta 2-microglobulin is a true secretory protein, and that its synthesis in hepatocytes is modulated by IFNs but not by IL-1. While the 45,000 MW HLA antigen can be found only in cell lysates, beta 2-microglobulin is shown to be secreted also into the culture medium like other secretory proteins (e.g. albumin-factor B-complement C3). Furthermore, interferon alpha (IFN alpha) as well as interferon gamma (IFN gamma) directly stimulate, in a dose- and time-dependent manner, beta 2-microglobulin synthesis by human hepatoma cells (Mz-Hep-1 and PLC/PRF5) and murine hepatocyte primary cultures. The increase of beta 2-microglobulin production induced by interferons is demonstrated at both the protein and the RNA level, indicating that interferon acts at a pretranslational level. The interferon effect on beta 2-microglobulin synthesis is specific since synthesis of secretory proteins like complement C3 or albumin, and of a structural protein like actin, remains unchanged. In contrast to IFN, IL-1, the main mediator of acute phase response, does not change beta 2-M biosynthesis rate. These data indicate that (i) beta 2-microglobulin is a secretory protein, (ii) IFNs but not IL-1 can mediate increased beta 2-M serum levels, and (iii) the liver may be its primary source.
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PMID:Alpha- and gamma-interferon (IFN alpha, IFN gamma) but not interleukin-1 (IL-1) modulate synthesis and secretion of beta 2-microglobulin by hepatocytes. 245 38

Recombinant human interferon alpha 2a as well as natural human interferons alpha and beta significantly suppressed the production of hepatitis B surface antigen by PLC/PRF/5 cells (which have been established from a human primary hepatocellular carcinoma and proven to carry the hepatitis B virus DNA) and inhibited proliferation of these cells in vitro. However, the production of alpha-fetoprotein by PLC/PRF/5 cells was less significantly affected by any of the interferons. These results suggest that these interferons not only suppress cellular proliferation but also selectively inhibit the action of the HBV gene which is persistently present in these cells.
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PMID:Suppression of HBsAg production in PLC/PRF/5 human hepatoma cell line by interferons. 246 37

Our study was undertaken to determine whether human recombinant interferon alpha(rIFN alpha), gamma(rIFN gamma), and tumor necrosis factor alpha(rTNF alpha) exert an effect on the HLA-A, B, C expression of human liver cell lines. The HLA-A, B, C expression was assayed by immunoperoxidase staining and enzyme-linked immunosorbent assay. rIFN alpha and gamma enhanced the HLA-A, B, C expression of the three cell lines tested, Chang cells, SK-Hep-1, and PLC/PRF/5. The activity of rIFN gamma proved more than 8000 times more potent than that of rIFN alpha in Chang cells, 30 times in SK-Hep-1, and 20 times in PLC/PRF/5, respectively. rTNF alpha also enhanced the HLA-A, B, C expression of the three cell lines. The enhancement of HLA-A, B, C expression by rIFN alpha and gamma reached a peak on day 3, and that by rTNF alpha on day 5. These findings suggest that IFN alpha, IFN gamma, and TNF alpha may play similar roles in enhancement of HLA-A, B, C expression of hepatocytes in hepatitis and hepatoma cells.
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PMID:Effect of interferon alpha, gamma, and tumor necrosis factor alpha on the HLA-A, B, C expression of cell lines derived from human liver. 249 41

Chronic hepatitis B virus (HBV) infection is a serious problem because of its world wide distribution and possible adverse chronic sequalae such as cirrhosis and hepatocellular carcinoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. Among immunomodulatory agents, levamisole, BCG, picibanil and interleukin-2 have been shown to be ineffective. Corticosteroid therapy is also ineffective and can cause deleterious effects in chronic HBV infection. Thymosin-alpha 1 therapy is currently in phase III clinical trial. Among antiviral agents, acyclovir, dideoxynucleosides, suramin, zidovudine and ganciclovir have been shown to be ineffective and have intolerable side effects. While adenine arabinoside (Ara-A) and its monophosphate derivative (Ara-AMP) are effective agents if the treatment course is long enough, they have been withdrawn from investigative use because of their substantial neuromuscular toxicity. Interferon-alpha may directly inhibit HBV replication and enhance hepatocyte HLA class I antigen expression with subsequent increase of T-cell mediated cytotoxicity. Randomized, controlled clinical trials have shown that 25% to 50% of adult patients with elevated alanine transaminase (ALT) levels lost HBeAg and HBV-DNA when treated with IFN-alpha at a dose of 5MU daily or 10 MU three times a week for 3 to 6 months. In view of the fact that the response rate is far from satisfactory, particularly in Asian patients, combination therapies including interferon alpha with Ara-AMP, acyclovir, didoxynucleoside or interferon-gamma have been studied. Most forms of combination therapy have been shown to be of limited effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Drug therapy in patients with chronic type B hepatitis]. 754 84

In hepatocarcinogenesis in rodents, induction of foci and nodules comprising clonally proliferated initiated cells is considered to be essential for the future development of carcinomas. Nodules in human cirrhotic liver, though known to be associated with a high hepatocellular carcinoma risk, have generally been regarded as regenerative in nature, and not the result of clonal or neoplastic cell proliferation, on a morphological basis. However, when we analyzed 83 cirrhotic nodules from 11 HBV carrier patients, utilizing hepatitis B virus (HBV) integration as a marker for clonal proliferation, we found the existence of clonal populations of more than 10(5) hepatocytes in 26 (31.3%) of them. Although such clonal cell populations are morphologically not discernible from neighboring hepatocytes, they may have particular histogenetic significance in human hepatocarcinogenesis and clearly deserve further investigation. Allelotype analysis of mouse hepatocellular carcinomas (HCC), induced by a single dose of diethyl nitrosaminine in C3H/MSM F1 hybrids, revealed no remarkable alterations in the original tumors when microsatellite probes were used, but loss of heterozygosity of chromosome 4 at extremely high frequency (95%) in cultured cell lines derived from these HCC. The shortest common region was about 10 cM distal to the interferon alpha gene, in which the p16 gene is located. The results indicated that loss of gene function, most probably including that of the p16 gene, may be essential for immortalization of cultured hepatocytes but that it may not play any role in initiation or early events in mouse hepatocarcinogenesis in vivo. The mouse HCC used for analysis in this study may be comparable with human HCC at an early stage, for which only very limited genetic alterations have so far been identified.
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PMID:Hepatocarcinogenesis in rodents and humans. 755 29

In 1988 investigators defined the agent causing most cases of non-A, non-B hepatitis and named this agent hepatitis C virus (HCV). Assays for antibody to HCV and more specific diagnostic tests (immunoblot and polymerase chain reactions) were subsequently developed. Exposure to HCV seems to result in chronic infection in a majority of cases, with progressive chronic liver disease sometimes leading to hepatocellular carcinoma. This virus is spread mainly by parenteral routes; intravenous drug users are at high risk. Sexual and intrafamilial spread has also been documented but seems to occur to a limited extent. Perinatal transmission, which is prominent in infection with hepatitis B virus, does not play an important role in the spread of HCV. Antiviral therapy with interferon alpha is usually tried in chronic hepatitis C but permanently normalizes liver function in only one-fourth of patients. The failure to demonstrate protective immunity after single or multiple episodes of infection raises doubts about the existence of neutralizing antibodies and concerns about the potential for the development of a vaccine against HCV.
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PMID:Hepatitis C: natural history of a unique infection. 762 24


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