Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present paper reviews several studies performed between 1977 and 1986 in Singapore on the 10-year survival outcome of treatment for stage I and II hepatocellular carcinoma (HCC). Of 801 HCC patients evaluated, only 2 survivors (0.3%) remained in complete remission for 13 and 14 years, respectively. One had received four weekly cycles of prednisolone, Adriamycin, vincristine and 5-fluorouracil for an inoperable HCC with a 10-cm diameter, and the other had received localised synchronised hepatic irradiation and Adriamycin. As follow-up, the use of localised hepatic irradiation consisting of 131I-labeled (30 mCi) iodised oil in lipiodol infused via the hepatic artery appeared to benefit patients with small residual tumours but did not affect larger tumours measuring 2 cm in diameter. Prophylactic, intermittent long-term administration of lymphoblastoid interferon-alpha (Wellferon) was carried out in pre-cancerous, high-risk hepatitis B surface antigen (HBsAg)-positive patients with cirrhosis, in immediate male relatives of liver cancer patients, and in persons who had undergone hepatic resection. In the untreated group, 10/162 (6%) cirrhotics, 3/18 (17%) male family members, and 6/10 (60%) post-resection cases developed single or multiple HCCs within 1 year of screening done at 3-month intervals on the basis of alpha-fetoprotein (AFP) levels and real-time hepatic ultrasonography. In contrast, none of the Wellferon-treated group consisting of 518 cirrhotic patients, 82 male relatives of HCC patients and 20 post-resection cases developed HCC. Two HBsAg-positive individuals who had not been treated with interferon (IFN) developed hepatic nodules which that showed dysplasia, AFP elevation and chromosomal changes. These studies demonstrate the poor results of late diagnosis and show that early intervention and prophylaxis with Wellferon can reduce the incidence of HCC in high-risk persons. In addition, transhepatic chemoembolisation and liver resection are suitable methods for treating small HCCs (single or multiple) that are detected by screening. However, some of these early-detected HCCs remain highly malignant. Prophylactic treatment of pre-cancerous conditions appears to be a better option as a long-term programme for HCC.
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PMID:Long-term survival following treatment of hepatocellular carcinoma in Singapore: evaluation of Wellferon in the prophylaxis of high-risk pre-cancerous conditions. 133

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.
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PMID:The use of interferon-alpha in virus infections. 172 72

Although interferon-alpha (IFN-alpha) has shown great promise in the treatment of chronic viral hepatitis, the anti-tumour effect of this agent in the therapy of liver cancer is unclear. Recent studies have demonstrated that differentiation-inducing agents could modulate the responsiveness of cancer cells to IFN-alpha by regulating the expression of signal transducers and activators of transcription (STAT) proteins, a group of transcription factors which play important roles in the IFN signalling pathway. We have reported that sodium butyrate is a potent differentiation inducer for human hepatoma cells. In this study, we investigated whether this drug could regulate the expression of STAT proteins and enhance the anti-tumour effect of IFN-alpha in hepatoma cells. We found that sodium butyrate specifically activated STAT1 gene expression and enhanced IFN-alpha-induced phosphorylation and activation of STAT1 proteins. Co-treatment with these two drugs led to G1 growth arrest, accompanied by down-regulation of cyclin D1 and up-regulation of p21WAF-1, and accumulation of hypophosphorylated retinoblastoma protein in hepatoma cells. Additionally, internucleosomal DNA fragmentation, a biological hallmark of apoptosis, was detected in hepatoma cells after continuous incubation with a combination of these two drugs for 72 h. Our results show that sodium butyrate potently enhances the anti-tumour effect of IFN-alpha in vitro and suggest that a rational combination of these two drugs may be useful for the treatment of liver cancer.
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PMID:Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-alpha. 1036 Jun 47

We investigated the expression of the drug resistance-related genes, multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), and the DNA topoisomerase IIalpha, DNA topoisomerase IIbeta, and glutathione-S-transferase pi gene (GST-pi) in three human hepatoma cell lines (HepG 2, HuH 7, SK-Hep-1) with or without drug treatment with interferon-alpha (IFN-alpha) and cisplatin (CDDP), by a reverse transcription-polymerase chain reaction (RT-PCR) method and a competitive PCR method. The signals of the MDR1, MRP, topoisomerase IIalpha, and topoisomerase IIbeta genes in HepG2 were weakened when IFN-alpha was added to CDDP. In SK-Hep-1, the administration of CDDP alone increased the signals of MDR1 while the addition of IFN-alpha decreased the signals, and the signals of GST-pi were decreased by IFN-alpha plus CDDP. In summary, our results concerning the expression of drug resistance-related genes in three human hepatoma cell lines demonstrate that IFN-alpha may modulate the mechanism of resistance to CDDP in liver cancer.
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PMID:Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines. 1043 11

A 62 year-old man was admitted to Asahikawa Medical College Hospital. Injection therapy of natural interferon-alpha was performed against chronic active hepatitis with hepatitis C virus infection. He successfully responded to interferon therapy with normalization of serum transaminases and disappearance of serum hepatitis C virus RNA. The liver function test remained within normal limits and serum hepatitis C virus RNA was not detected throughout the observation period. Three years later, CT examination demonstrated 2 small hepatic masses. Ultrasound-guided biopsy of the hepatic mass demonstrated well-differentiated hepatocellular carcinoma histologically. Laparoscopic examination revealed chronic hepatitis, but neither active inflammation nor cirrhotic changes were noted as an underlying liver disease. In the liver specimen, hepatitis C virus RNA was not detected by RT-PCR. Percutaneous ultrasound-guided ethanol injection therapy achieved complete necrosis of the hepatocellular carcinoma and there was no recurrence of hepatic cancer during the follow-up period. This case suggests that patients with chronic hepatitis C infection, who have complete disappearance of serum hepatitis C virus RNA by interferon therapy, should be followed-up carefully for the potential development of hepatocellular carcinoma.
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PMID:Hepatocellular carcinoma developed in a patient with chronic hepatitis C after the disappearance of hepatitis C virus due to interferon therapy. 1052 40

Human E-cadherin is a homophilic cell adhesion molecule and its expression is well preserved in normal human hepatocytes; a decrease in its expression has been observed in poorly differentiated hepatocellular carcinoma cells. We examined the alteration of E-cadherin and catenin expressions caused by differentiation inducers in human hepatocellular carcinoma cells. Hepatocellular carcinoma cell lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA), dexamethasone (DEX), sodium butyrate, and interferon-alpha. E-cadherin expression was only up-regulated by butyrate and interferon-alpha (IFN-alpha) in both cell lines, studied by means of fluorescence immunostaining and flow cytometry. The localization of E-cadherin staining was shown at their cell membrane. According to the increase in E-cadherin expression, beta-catenin expression appeared at the cell membrane of both cell lines when treated with butyrate and IFN-alpha. Such an appearance was not observed when cells were treated with ATRA and DEX. Western blotting showed that alpha- and y-catenin expression was not changed, while only the expression of beta-catenin increased. Beta-catenin oncogenic activation as a result of amino acid substitutions or interstitial deletions within or including parts of exon 3, which has been demonstrated recently, was not detected in these cell lines by direct deoxyribonucleic acid sequencing. These results suggest that the expression and interaction between E-cadherin and wild-type beta-catenin are potentially modulated by butyrate and IFN-alpha, and that these two agents are potent inhibitors of hepatocellular carcinoma cell invasion and metastasis.
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PMID:Up-regulation of E-cadherin and I-catenin in human hepatocellular carcinoma cell lines by sodium butyrate and interferon-alpha. 1094 98

The prevalence of hepatitis B infection in population in Poland is low and averages 1-1.5%. However, it means that about 380,000 Poles constantly or temporarily replicate HBV. Chronic HBV infection is associated with increased risk of serious liver diseases and it is estimated that 25-40% of patients with chronic hepatitis B will die prematurely of cirrhosis or primary liver cancer. Up to the present, interferon-alpha (IFN-alpha), with low response rate between 25-55% and some limitations of therapy, has been the only available treatment for chronic hepatitis B. A favorable outcome of IFN-alpha therapy is associated with some prognostic factors, not accepted by all investigators, such as low level of HBV-DNA in serum. The aim of this study was to assess the efficacy of therapy with IFN-alpha 2b (Intron A), administered s.c. 5 MU x 3/week for 16 weeks, in 65 patients with chronic hepatitis B, divided into groups according to the baseline HBV-DNA level. Except for serum HBV-DNA level, there were no demographical and biochemical differences between all the treated groups. The patients were followed-up for 12 months. Sustained response (SR) to the therapy (defined as ALAT normalization, loss of detectable HBV-DNA, seroconversion HBeAg to anti-HBeAg and improvement in liver histology) was observed in 16 (57.14%) of patients in the group with HBVDNA level < 1000 pg/ml, in 6 (37.5%) with HBV-DNA level of 1001-3000 pg/ml, in 4 (28.57%) with HBV-DNA level of 3001-5000 pg/ml and only in 2 (28.57%) of patients in group with HBVDNA level > 5000 pg/ml. We conclude that IFN-alpha is particularly useful in therapy of patients with chronic hepatitis B with low levels of HBV-DNA. The baseline HBVDNA level < 1000 pg/ml in serum is the predictor of good response to IFN-alpha therapy.
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PMID:HBV-DNA level in blood serum as a predictor of good response to therapy with interferon-alpha-2b of patients with chronic hepatitis B. 1120 40

The immune systems of most adults can suppress the hepatitis B virus (HBV), but 2 percent to 20 percent of HBV-infected adults experience a persistent or chronic infection. About one-third of those with chronic infection remain otherwise healthy, while two-thirds may experience severe liver damage or liver cancer. Antiviral therapy being tested for HBV suppression includes interferon-alpha with or without 3TC or famciclovir (Famvir). In addition, researchers are now studying the immune systems of people able to fight the infection, hoping to translate those findings into more effective treatments for HBV. Details are also included on a recent study in which patients were given GenHevac B or Recombivax for HBV treatment. The data suggest the vaccines helped subjects to recognize and fight the infection, by improving the ability of CD4+ cells to control the virus. Final study results have not yet been published.
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PMID:Vaccine therapy for hepatitis B? 1136 30

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

We have demonstrated anti-proliferation and anti-metastasis effects of both interferon-alpha and a histone deacetylase inhibitor, sodium butyrate, on human liver cancer cell lines. In this study, invasive ability of human liver cancer cell lines through the matrix-coated membrane was examined and inhibitory effect of interferon-alpha and sodium butyrate was investigated. Among six human liver cancer cell lines, HLE and HLF showed high invasive ability using the Matrigel invasion assay. This invasion ability was significantly inhibited by pretreatment of the cells with 1000 IU/ml of interferon-alpha or 2 mM of sodium butyrate. Gelatin zymography and the matrix metalloproteinase-2 and -9 activity assay showed that these two cell lines produce active- and pro-matrix metalloproteinase-2 and -9, and their activity was significantly reduced by pretreatment with both agents. Real-time quantitative reverse transcription-polymerase chain reaction showed decrease in matrix metalloproteinase-1 mRNA levels by pretreatment with both agents, but mRNA levels of tissue inhibitor of matrix metalloproteinase-1 and -2 were differently modulated by interferon-alpha and sodium butyrate. These results suggest that interferon-alpha and sodium butyrate reduce a chance of invasion and metastasis of human liver cancer cells by inhibiting matrix metalloproteinase activity, although its inhibitor is differently regulated.
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PMID:Down-regulation of matrix-invasive potential of human liver cancer cells by type I interferon and a histone deacetylase inhibitor sodium butyrate. 1501 Aug 20


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