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

Human hepatitis B virus encodes a secretory core protein, referred to as the HBe protein, whose secretion is mediated by the pre-C signal sequence. Here we examined whether this sequence is important only for translocation of the HBe precursor (the precore protein) or whether it also contributes to the structural and biophysical properties of the mature HBe protein. When a truncated hepatitis B virus precore protein, lacking the basic C-terminal domain which is cleaved from the wild-type protein during its conversion into HBe, was expressed in human hepatoma cells, only a small amount of HBe-like protein was produced. This protein was slightly smaller than the wild-type HBe protein, suggesting that C-terminal cleavage of the precore protein does not occur at the suggested site. When the authentic signal sequence of the precore protein (the pre-C sequence) was replaced by the unrelated signal sequence of an influenza virus hemagglutinin, not only the full-length but also the C-terminally truncated protein was expressed and secreted with high efficiency. Western blot (immunoblot) analyses with nonreducing gels and conformation-specific monoclonal antibodies revealed that the HBe protein secreted under control of the pre-C signal sequence was a monomer with HBe antigenicity, whereas the HBe-like protein secreted under control of the hemagglutinin signal sequence was a disulfide-bridge-linked dimer with both HBe and HBc antigenicity. Electron microscopic examination of gradient-purified particulate core gene products showed that HBe protein secreted under control of the hemagglutinin signal sequence forms core particles, whereas HBe protein secreted under control of the pre-C sequence does not. Thus, the pre-C sequence not only mediates the secretion but also determines the structural and aggregational properties of the HBe protein.
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PMID:The quaternary structure, antigenicity, and aggregational behavior of the secretory core protein of human hepatitis B virus are determined by its signal sequence. 194 54

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

Twenty-six patients with advanced cancer received monthly intramuscular recombinant leukocyte A interferon (IFN-alpha 2A), 12 X 10(6) U/m2 daily X 5 with escalating doses of doxorubicin, 25 to 40 mg/m2 on day 3. As anticipated, dose-limiting toxicities were an influenza-type syndrome and myelosuppression. A clinically meaningful and dramatic partial response of hepatocellular carcinoma persisted for 11.5 months associated with an alpha-fetoprotein reduction from 39,000 to 299 ng/ml. For Phase II investigations, the authors recommend the above IFN-alpha 2A dose with doxorubicin, 40 mg/m2, in patients with a performance score of 0 or 1 and no prior chemotherapy or significant radiation therapy which would enhance myelosuppression.
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PMID:Phase I study of recombinant leukocyte A interferon (IFN-alpha 2A, Roferon-A) with doxorubicin in advanced malignant disease. 247 65

Population density and immune status, vectors and virulence of infection, nutritional status, sanitation, genetic susceptibility and medical management of cases, are important factors influencing the incidence and/or severity of virus infections. Thus, the prevalence and clinical importance of virus infections and the need for antiviral drugs differ from place to place and from time to time. National and World Health Statistics of notifications of disease give some index of the incidence of infections but not all virus infections are notifiable. Such statistics can be misleading also through failures to notify from sloth on the part of the physician or, in the absence of pathognomonic symptoms or signs, from errors in diagnosis. Any assessment of the need for new antiviral drugs should consider the availability, safety, effectiveness and cost of alternative measures, including prevention of spread of infection by control of vectors, immunization by use of viral vaccines, or treatment with existing antiviral drugs. Early start of treatment of acute virus infections with existing drugs gives the best results and, where the clinical diagnosis is uncertain, accurate rapid virus diagnosis is of paramount importance. Many virus infections are asymptomatic or of trivial importance and without sequelae. However, new or improved antiviral drugs are needed for the prevention and/or treatment of a number of significant conditions caused by viruses which are not at present adequately controlled. These include upper and lower respiratory tract infections, influenza, chronic hepatitis, gastroenteritis, infectious mononucleosis, measles, rabies, haemorrhagic fevers and warts. Furthermore, such drugs might prove of therapeutic value in the prevention or treatment of virus-associated tumours, such as hepatoma, nasopharyngeal carcinoma, Burkitt's lymphoma, Kaposi's sarcoma and possibly carcinoma of the cervix.
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PMID:The need for new antiviral agents. 300 26

In Southeast Asia, 15 to 20 percent of the population are hepatitis B surface antigen carriers. The majority of these carriers have chronic hepatitis and would progress to cirrhosis or hepatocellular carcinoma at an annual incidence of 2 percent and 1 percent, respectively. Previous studies from Southeast Asia suggested that immunosuppressive therapy could be harmful, or at best of no value, and antiviral treatment with vidarabine, picibanil, or even interferon was also unsatisfactory. Currently, a randomized controlled trial of human lymphoblastoid interferon, with or without prednisolone pretreatment, versus placebo in patients with hepatitis B core antigen in the liver and hepatitis B e antigen in the serum is being conducted. Forty-five patients (29 receiving interferon, 16 receiving placebo) have been entered in the trial for at least two months. Actuarial analysis shows that the response to interferon therapy was better than that to placebo. Although flu-like symptoms, hair loss, and body weight loss were seen, no side effect requiring specific treatment has been encountered. These preliminary results suggest that human lymphoblastoid interferon is effective and safe in Oriental patients.
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PMID:Treatment of chronic type B hepatitis in Southeast Asia. 304 79

We have defined the expression of the mRNA for, and secretion of, IFN-beta 2/hepatocyte-stimulating factor/IL-6 (IFN-beta 2/IL-6) in human diploid fibroblasts (FS-4 strain) infected with different RNA- and DNA-containing viruses. RNA blot-hybridization analyses carried out 6-8 h after the beginning of infection showed that the RNA-containing Sendai virus (paramyxoviridae) enhanced IFN-beta 2/IL-6 mRNA levels 10-fold, followed, in decreasing order, by encephalomyocarditis (EMC, picornaviridae), vesicular stomatitis (VSV, rhabdoviridae), Newcastle disease virus (NDV, paramyxoviridae), and influenza A (Flu, myxoviridae) viruses. The DNA-containing pseudorabies virus (PR, herpesviridae) enhanced IFN-beta 2/IL-6 mRNA levels sixfold, while the effect of adenovirus type 5 (Ad5, adenoviridae) was considerably less and comparable with that of NDV or Flu. A rabbit antiserum raised against E. coli-derived human IFN-beta 2/IL-6 was used in immunoprecipitation experiments to monitor the secretion of 35S-methionine-pulse-labeled IFN-beta 2/IL-6 proteins by fibroblasts up to 7 h after the beginning of infection. Enhanced levels of secretion of IFN-beta 2/IL-6 (2-14-fold) were observed in every instance evaluated (Sendai, EMC, VSV, Flu, PR, Ad5 viruses). A biological consequence of enhanced secretion of IFN-beta 2/IL-6 was the ability of media from infected FS-4 cell cultures to enhance by 8-15-fold the synthesis and secretion of a typical acute phase plasma protein (alpha 1-antichymotrypsin) by human hepatoma Hep3B2 cells. These observations make it likely that IFN-beta 2/IL-6 mediates, in part, the host response to acute virus infections.
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PMID:Regulation of the acute phase and immune responses in viral disease. Enhanced expression of the beta 2-interferon/hepatocyte-stimulating factor/interleukin 6 gene in virus-infected human fibroblasts. 313 43

Incubation of fluorescently labeled influenza virus particles with living cultured cells such as lymphoma S-49 cells or hepatoma tissue culture cells resulted in a relatively high degree of fluorescence dequenching. Increase in the degree of fluorescence (35-40% fluorescence dequenching) was observed following incubation at pH 5.0 as well as at pH 7.4. On the other hand, incubation of fluorescently labeled influenza virions with erythrocyte ghosts resulted in fluorescence dequenching only upon incubation at pH 5.0. Only a low degree of fluorescence dequenching was observed upon incubation with inactivated unfusogenic influenza or with hemagglutinino-influenza virions. The results of the present work clearly suggest that the fluorescence dequenching observed at pH 5.0 resulted from fusion with the cells' plasma membranes, while that at pH 7.4 was with the membranes of endocytic vacuoles following endocytosis of the virus particles. Our results show that only the fluorescence dequenching observed at pH 7.4--but not that obtained at pH 5.0--was inhibited by lysosomotropic agents such as methylamine and ammonium chloride, or inhibitors of endocytosis such as EDTA and NaN3.
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PMID:Quantitative determination of virus-membrane fusion events. Fusion of influenza virions with plasma membranes and membranes of endocytic vesicles in living cultured cells. 362 62

Sialyltransferase was measured in serum of normal and hepatoma Mc-29 bearing chickens. By preparative isoelectric focusing the multiple forms of sialyltransferase from both kind of serums was studied as well. By using influenza virus neuraminidase an attempt was made for partial structural characterization of the sialylation sites in asialofetuin applied as exogenous acceptor for sialyltransferase determination. It was established an elevated serum sialyltransferase activity in tumor bearing chickens with tumor an enzyme form was detected with pI-4.99 identical with an enzyme form described previously in solubilized plasma membrane preparations from hepatoma Mc-29. Monitoring of multiple forms of serum glycosyltransferases may be of value in answering the problem concerning the tissue origin of serum enzymes.
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PMID:Characterization of sialyltransferases from serum of normal and hepatoma Mc-29 bearing chickens. 395 42

Ceftizoxime (CZX), a parenteral cephalosporin derivative belonging to the so-called third generation cephalosporin is reported to have a broad antibacterial activity, particularly against Gram-negative aerobic bacilli and some anaerobes, such as Bacteroides fragilis and a good stability to beta-lactamases. Clinical study was performed on a total of 20 cases, 9 females (1 case had urinary tract infection 3 times) and 11 males, aged from 27 to 82 years. All patients had the underlying diseases. They were bronchial asthma in 3 cases, influenza in 1, chronic pulmonary emphysema in 1, pulmonary fibrosis in 1, chronic bronchitis with strongyloidiasis in 1, lung cancer in 3, esophagus cancer in 2, stomach cancer in 1, hepatoma with urolithiasis in 1, liver cirrhosis with diabetes mellitus in 1, alcoholism with strongyloidiasis in 1, cholelithiasis in 1 and congestive heart failure in 1, respectively. Clinical diagnoses for infections were 2-acute bronchitis, 2-exacerbation of chronic bronchitis, 2-broncho-pneumonia, 2-pneumonia including one suspected case, 1-obstructive pneumonia, 2-secondary pulmonary infection, 1-pulmonary infection, 3-urinary tract infection (UTI), 1-UTI with sepsis, 1-sepsis, 1-sepsis with purulent meningitis, 1-biliary tract infection and 1-infected bronchoesophageal fistula. CZX was given by intravenous drip infusion, at a dose of 1 to 2 g, twice daily for 3 to 15 days. Because of severity in infections and underlying diseases, some cases were treated either steroid, gamma-globulin preparations or other antibiotics in combination with CZX. Twelve out of 15 cases assessed clinically responded satisfactorily to the treatment and efficacy rate was 80.0%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effectiveness of ceftizoxime on various infections in patients with underlying diseases]. 609 Jul 23


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