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)

Interleukin-1 (IL-1) production by monocytes of patients with various forms of malignant disease was measured after activating the cells with either lipopolysaccharide or malignant K562 cells. Monocytes from all the patients with large tumour masses, including 10 patients with hepatocellular carcinoma, produced considerably less IL-1 than controls or patients with small tumour burdens. After treating control or patient monocytes with human leucocyte interferon for 1 h prior to activation, IL-1 production was markedly improved. Depressed IL-1 production is, therefore, a further aberration in mononuclear function observed in patients with cancer.
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PMID:Defective interleukin-1 production by monocytes from patients with malignant disease. Interferon increases IL-1 production. 660 4

The antitumor effect of human fibroblast interferon (HuIFN-beta) was examined using a nude mouse-human tumor xenograft group. Eight subcutaneously transplanted tumors--one line each of ovarian carcinoma, laryngeal carcinoma, carcinoma of the nasopharynx and hepatoma, and two lines each of lung carcinoma and melanoma--were used. HuIFN-beta at 1 X 10(5) IU/mouse was injected subcutaneously around the tumor or into the tumor itself. In the former case, statistically significant growth-suppressive effects were observed in one lung carcinoma (PC-12) and both melanomas (AM-1 and SK-14), but no effect was seen on the other five tumors. Further studies were made to ascertain the effects of intratumoral injections. Increased growth inhibition was observed in both melanomas (AM-1 and SK-14), but not in lung cancer (PC-12). Complete regression was seen in 3 of 8 mice carrying SK-14. The sensitivity of tumors to HuIFN-beta was correlated to the inhibitory effect of HuIFN-beta on cell division detected by histological observation.
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PMID:Effects of human fibroblast interferon on human tumors transplanted into nude mice: sensitivity of human tumors to interferon. 716 May 83

We investigated the expression of intercellular adhesion molecule 1 (ICAM-1) in ex vivo human hepatocellular carcinoma (HCC) cells and in vitro in eight liver cancer cell lines, including six HCC cell lines and two combined hepatocholangiocarcinoma (CHC) cell lines. Immunohistochemistry showed the expression of ICAM-1 on the HCC cell surface with honeycomblike appearance in most cases (96.2%). On the other hand, hepatocytes in noncancerous areas did not express ICAM-1, except those hepatocytes in the periportal and intra-acinar areas with inflammation. Immunohistochemical study on cultured cells revealed that four cultured HCC cell lines and one CHC cell line constitutively expressed ICAM-1 on the cell surface and in the cytoplasm. Flow cytometric analysis revealed that immunostain-positive cells expressed surface ICAM-1 with more than a 90% positive cell rate, and their expressions were upregulated by incubation of cells with inflammatory cytokines, such as interferon alfa, interferon gamma, tumor necrosis factor-alpha, and interleukin 1 beta. Soluble ICAM-1 was detected in supernatants of cell lines expressing cell surface ICAM-1 expression, and was increased in amounts 2- to 20-fold by inflammatory cytokines. These findings suggest that liver cancer cells in ex vivo may express not only surface but also a soluble form of ICAM-1, differently from normal hepatocytes, and that both expressions are upregulated by inflammatory cytokines.
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PMID:Expression of intercellular adhesion molecule 1 in human hepatocellular carcinoma. 748 78

Interleukin-6 (IL-6) and gamma interferon (IFN-gamma) induce a partially overlapping set of genes, including the genes for interferon regulatory factor 1 (IRF-1), intercellular adhesion molecule 1 (ICAM-1), and the acute-phase protein alpha 2-macroglobulin. We report here that the rat alpha 2-macroglobulin promoter is activated by IFN-gamma in human hepatoma (HepG2) cells and that the IFN-gamma response element maps to the same site previously defined as the acute-phase response element (APRE), which binds the IL-6-activated transcription factor APRF (acute-phase response factor). As was reported for fibroblasts, the IFN-gamma-regulated transcription factor GAF is phosphorylated at tyrosine after IFN-gamma treatment of HepG2 cells. IFN-gamma posttranslationally activates a protein which specifically binds to the alpha 2-macroglobulin APRE. This protein is shown to be identical or closely related to GAF. Although APRF and GAF are shown to represent different proteins, their binding sequence specificities are very similar. APRF and GAF bind equally well to the APRE sequences of various acute-phase protein genes as well as to the IFN-gamma response elements of the IRF-1, ICAM-1, and other IFN-gamma-inducible genes. Transient transfection analysis revealed that the IFN-gamma response elements of the IRF-1 and ICAM-1 promoters are able to confer responsiveness to both IFN-gamma and IL-6 onto a heterologous promoter. Therefore, APRF and GAF are likely to be involved in the transcriptional induction of these immediate-early genes by IL-6 and IFN-gamma, respectively. Taken together, these results demonstrate that two functionally distinct hormones, IL-6 and IFN-gamma, act through common regulatory elements to which different transcription factors sharing almost the same sequence specificity bind.
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PMID:The signalling pathways of interleukin-6 and gamma interferon converge by the activation of different transcription factors which bind to common responsive DNA elements. 750 45

The methods for diagnosing hepatitis C virus infection have been evolving since the first-generation enzyme-linked immunosorbent assay antibody test was devised in 1989. In addition to assaying for serum antibodies against viral proteins, serum and liver tissue can be tested for viral RNA, evidence of ongoing viral replication. The improving ability to diagnose hepatitis C has furthered the understanding of the natural history of this infection. Acute hepatitis C results in chronic elevations of serum transaminase levels following nearly one half of cases. Cirrhosis complicates approximately 20% of chronic infections. Long-standing chronic hepatitis C may play a role in the pathogenesis of hepatocellular carcinoma. Sustained normalization of serum transaminase levels, often accompanied by a decrease in or disappearance of viral RNA, occurs in approximately 25% of patients with chronic hepatitis C who are treated with a 6-month course of recombinant interferon alfa. This treatment can occasionally be complicated by hematologic, endocrinologic, and psychiatric adverse effects but is usually fairly well tolerated. Whether interferon therapy will diminish the risk of cirrhosis or carcinoma is not yet known. This article reviews the diagnosis of chronic hepatitis C infection as well as the mechanisms of action, efficacy, and adverse effects associated with interferon alfa therapy.
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PMID:Chronic hepatitis C. Advances in diagnostic testing and therapy. 750 93

The concentration of Hepatitis C Virus (HCV) in the blood is increased by alcohol drinking and decreased by abstinence. These facts suggested that alcohol abuse may enhance the replication of HCV. The effects of alcohol on HCV replication may be related to increased development of chronic hepatitis to liver cirrhosis and hepatocellular carcinoma in HCV marker positive heavy drinker. These results indicated that HCV positive heavy drinkers must keep abstinence and that these patients have to be treated with interferon.
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PMID:[Effects of interferon treatment in alcoholic liver injury]. 752 33

Fifty-five clones encoding epitopes of HCV were isolated from Japanese patients. Their amino acid homology (AAH) to the sequence of prototype (HCV-1) ranged from 47% to 94%. These sequences cover 60% of the HCV genome lacking M/E and NS2 regions suggesting a very low or lacking immunogenicity for these regions. Two test kits for detection of anti-HCV antibody were developed using a combination of a synthetic peptide (AR142) containing the epitope of N14 (QRKTKRSTNRR) having a homology to the core of HCV of 8/11AA and a non-fusion recombinant protein Y19 starting from amino acid number (AAN) 1380 to 1507 in the NS3 region showing a AAH to the HCV-1 of 90%, and a combination of a mixture of three synthetic peptides of S29 AAN of 1-30, 38-65 and 47-74 of the core and a non-fused recombinant protein S4 AAN of 1287-1506 having a 93% AAH of the NS3 region. They showed almost the same order of sensitivity and specificity of the second-generation kits when tested with serum from blood donors and patients with non-A, non-B hepatitis. It should also be stressed that in all of the complete responders of a recombinant alpha-interferon therapy, the antibody levels against AR142 gradually decreased during and after the treatment. In 1992, studies performed for 125 patients with hepatocellular carcinoma in our clinic shows that of these 16 patients might developed from either chronic non-B, non-C liver diseases or chronic liver diseases caused by mutant(s) of HCV as their serum were negative for HBsAg and second-generation of anti-HCV.
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PMID:Molecular cloning of HCV and clinical application. 752 19

Based on the in vitro and in vivo potentiation of the cytotoxic activity of chemotherapeutic agents by the interferons, a pilot study combining human recombinant alpha-2b interferon (IFN) and doxorubicin was conducted for the treatment of unresectable, histologically proven hepatocellular carcinoma. Between March 1988 and May 1990, 21 patients (median age: 60 years, range: 29-76) entered the study. The dose of doxorubicin was fixed at 35 mg/m2, every 3 weeks. The dose of alpha-2b IFN was 6 million U/m2 per day, 5 days a week. 3 patients (14%) obtained a partial response lasting 11, 16 and 30 months, and 1 had a stable disease during 8 months. The other 17 patients died within a median survival time of 4 months. All patients experienced flu-like symptoms. 7 patients experienced WHO grade III-IV haematological toxicity. We conclude that the association of alpha-2b IFN and doxorubicin is feasible, with respect to the use of doxorubicin at an inferior dose level than the same agent used without IFN. The response rate is comparable to that observed with doxorubicin used alone. Further phase I studies and randomised trials are required to confirm the role of this regimen in the treatment of unresectable hepatocellular carcinoma.
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PMID:Treatment of unresectable hepatocellular carcinoma with a combination of human recombinant alpha-2b interferon and doxorubicin: results of a pilot study. 752 30

Interferon is currently the only established therapeutical option for chronic viral hepatitis. Sustained response can be achieved in approximately 25% of patients with chronic HBV or HCV infection. Results in chronic HDV infection are disappointing. Whether combination of interferon with other lymphokines or antiviral drugs will lead to higher response rates, remains to be established. The argument that interferon will only place spontaneous seroconversion on an earlier date has not been disproved yet. Long-term follow-ups are necessary to show that therapy with interferon will improve survival and reduce the incidence of hepatocellular carcinoma in patients with chronic viral hepatitis.
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PMID:Therapy of chronic viral hepatitis. 753 38

Hepatitis C virus (HCV) populations in vivo exist as a mixture of heterogeneous viruses called quasispecies, which have variations in the hypervariable region (HRV). However, the relationship between the diversity of HVR quasispecies, the disease stage, or the interferon (IFN) responsiveness remains to be elucidated. To study these, serum samples were obtained from 42 patients with chronic hepatitis C virus infection; 24 with chronic active hepatitis (CAH) treated with IFN, 9 with cirrhosis, 9 with hepatocellular carcinoma (HCC). HCV quasispecies populations were separated by the single-strand conformation polymorphism (SSCP) method targeted to the HVR. The patients were classified into two groups; a single-band group (n = 12) in which HVR quasispecies was homogeneous and a multiple-band group (n = 30) in which HVR quasispecies was heterogeneous. Patients with multiple bands had significantly more advanced liver disease than those with a single-band group (P = .0082). The percentage of patients with single band were 41% in CAH, 22% in cirrhosis, and 0% in HCC. Multivariate analyses showed that viral diversity was independently related to the progression of liver disease and was not correlated with the duration of infection. We also found that in CAH, the patients who had multiple bands (n = 14) were more resistant to IFN therapy than those who had a single band (n = 10) (P = .002). These results indicate that the diversity of HCV quasispecies becomes more complex as the disease stage progresses and that CAH with more complex diversity shows less IFN effectiveness.
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PMID:Diversity of quasispecies in various disease stages of chronic hepatitis C virus infection and its significance in interferon treatment. 754 87


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