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)

Five patients with hepatitis B surface antigen (HBsAg) positive chronic hepatitis and histologically confirmed primary hepatocellular carcinoma (PHC) were treated with 3 X 10(6) units/day of partially purified human leukocyte interferon intramuscularly for 2 consecutive months. During interferon therapy, one patient had stable disease, while the remaining four patients had progressive disease. Following interferon therapy no changes were noted in the hepatitis B viral markers or in serum alphafetoprotein levels. Data on the effects of human leukocyte interferon on lymphocyte subpopulations and on the cytotoxic activity of peripheral blood mononuclear cells against a hepatitis B surface antigen expressing primary hepatocellular carcinoma cell line are presented.
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PMID:Clinical, serologic, and immunologic effects of human leukocyte interferon in HBsAg-positive primary hepatocellular carcinoma. 299 Jun 62

Antibody profiles for cytomegalovirus (CMV), hepatitis A virus (HAV), hepatitis B virus (HBV) and the delta-agent were determined on 55 serum samples drawn from 55 Saudi patients on maintenance haemodialysis for periods ranging from 1.5 months to 2 years. The exposure rates for CMV, HAV, and HBV were 100%, 100%, and 72.7%, respectively. There was no intersex difference in positivity for HBV surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to HBV core antigen (anti-HBc); 15.4%, 65.4%, 3.8% in males and 6.9%, 55.2%, and 0% in females, respectively. Among six HBsAg carriers, one and three were positive for e antigen (HBeAg) and antibody to HBeAg (anti-HBe), respectively, with two negative for HBeAg and anti-HBe. The six carriers were also negative for anti-delta antibody. A comparison of the above antibody profile to the profile of voluntary blood donors and those seeking treatment for minor ailments in the local general hospital, obtained earlier using identical test procedures, revealed no difference for CMV and HAV exposure rate. The HBV exposure rate was higher in the haemodialysed patients (P less than 0.001). The epidemiological measures for preventing nosocomial viral hepatitis including immunisation of susceptibles, can be supplemented, among carriers, by interferon and acyclovir therapy for active viral replication. In HBV hyperendemic areas, haemodialysis patients exposed to HBV should be screened periodically for early signs of hepatocellular carcinoma.
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PMID:Viral hepatitis markers in patients on haemodialysis in a hyperendemic area. 300 4

We have examined the growth inhibitory effects of human lymphoblastoid interferon (IFN) on the human hepatocellular carcinoma (HCC) cell line PLC/PRF/5. In vitro, PLC/PRF/5 cells were sensitive to the antiproliferative effects of IFN, growth inhibition being noted at concentrations as low as 1.25 i.u. ml-1. Athymic mice with xenografted tumours derived from the PLC/PRF/5 cell line were treated daily with IFN or a saline control. An IFN dose of 2 X 10(5) i.u./day was found capable of significantly slowing tumour growth rate and prolonging mouse survival. Further studies to examine the mechanisms involved in growth inhibition in vivo demonstrated that IFN was capable of inducing the activity of the enzyme 2,5-oligoadenylic acid (2,5 A) synthetase, a potent inhibitor of protein synthesis, in tumour xenografts but not in mouse tissue, and that IFN significantly enhanced the membrane display of HLA class I glycoproteins on tumour cells, though histology did not reveal any increase in tumour infiltration by host lymphocytes. We conclude that IFN exerts potent growth inhibitory effects on the HCC cell line PLC/PRF/5 both in vitro and in vivo and its mode of action in this animal model system appears to be predominantly mediated by a direct antiproliferative effect on tumour cells.
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PMID:Human lymphoblastoid interferon. In vitro and in vivo studies in hepatocellular carcinoma. 301 85

Sera from 31 HBsAg-positive Chinese patients with inoperable hepatocellular carcinoma (HCC) were tested for hepatitis B virus DNA (HBV DNA) by means of dot hybridisation and Southern blot technique. HBV DNA probes were prepared from human plasma. Eighteen of the patients were HBeAb-positive, 12 were HBeAg-positive and one case had neither marker. Serial specimens were obtained from 16 cases over 5-42 weeks, while the patients were treated with recombinant leukocyte A interferon (rIFN-A) or adriamycin. Seven patients (2 HBeAg-positive, 5 HBeAb-positive) were positive for HBV DNA. In two patients HBV DNA and HBV DNA polymerase (DNAp) appeared in serum weeks after rIFN-A or adriamycin treatment was started. In two other cases, HBV DNA that was initially present disappeared during rIFN-A treatment. In a fifth patient HBV DNA persisting after adriamycin treatment diminished after change of treatment to rIFN-A. With one possible exception the HBV DNA detectable by Southern blot technique was composed chiefly of sequences 2.2-3.2 kb size indicating the presence of unintegrated DNA forms. DNAp activities were raised in the presence of HBV DNA in 4 patients. These findings show that HBV replication can be activated or suppressed in advanced HCC. Treatment with rIFN-A may have been effective in suppressing HBV DNA synthesis, but the number of cases studied was too small to arrive at a definite conclusion on this point.
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PMID:Serum hepatitis B viral DNA in HBsAg-positive hepatocellular carcinoma treated with interferon or adriamycin. 301 83

An in vitro cell culture system utilizing continuous human liver cells has been developed which, upon specific induction, will respond by synthesizing, de novo, the prototype acute phase reactant, C-reactive protein (CRP). Induction of CRP in vitro is not brought about by the types of hormones, steroids, and chemicals which affect other acute phase proteins. In particular, interleukin-1 thought to be directly responsible for acute phase induction is not found to be active. Direct testing of other purified biological response modifiers, i.e. alpha, beta, and gamma-interferon, interleukin-2, and tumor necrosis factor, demonstrates no inducing activity. However, we find that human peripheral blood monocytes, stimulated by endotoxin, produce a factor(s) which directly induces CRP synthesis in hepatoma cells. In addition, the human promyelocyte-like cell line HL-60 in the presence of phorbol ester and certain T-cell lines containing human retroviruses also produce this CRP-inducing factor(s). Isolation and partial purification of the CRP-inducing factor(s) indicate that it is a protein(s) with a molecular weight of approximately 30,000.
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PMID:Biosynthesis of human C-reactive protein in cultured hepatoma cells is induced by a monocyte factor(s) other than interleukin-1. 302 76

Hepatitis B virus (HBV) infection is prevalent in Chinese populations. 40.4% of 383 Chinese HBV carriers studied were HBeAg-positive. The annual rate of spontaneous clearance of HBeAg was 11%. Twenty-six patients with HBsAg- and HBeAg- and HBeAg-positive non-malignant chronic liver disease randomised to receive recombinant alpha-2 interferon or no treatment have been followed for 6 months or longer. Seven of the 20 treated patients cleared HBeAg during or shortly after treatment but this was sustained in only 1 patient. One of the 6 controls had transient loss of HBeAg. It is too early to conclude whether interferon has any long-term effect on the suppression of HBV replication in Chinese patients. Sixty-nine patients with histologically proven hepatocellular carcinoma were randomised to receive adriamycin or interferon. Although there was no significant benefit on survival, interferon therapy was associated with greater than 25% regression in tumor size in 12.5% of patients and less toxicity.
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PMID:Interferon therapy of chronic hepatitis B virus infection in Chinese. 303 36

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

Using the human tumor clonogenic assay technique, the combined effects of mitomycin C (MMC) with alpha-interferon (HLBI) were surveyed in comparison with 33 fresh human tumor specimens. Tumors in this study were 16 gastric cancers, five breast cancers, four liposarcomas, three colon cancers, two gall bladder cancers, two esophageal cancers, and one hepatoma. When the survival fraction observed in drug combination was smaller than the multiplication of each survival fraction observed in each drug alone, the combined effects were considered to be synergistic. Twenty-two of 33 tumors (gastric cancer 11/16, breast cancer 5/5, liposarcoma 2/4, colon cancer 1/3, gall bladder cancer 2/2, esophageal cancer 1/2, and hepatoma 0/1) formed adequate colony numbers for the evaluation of combined drug effects. Synergistic effects were observed in seven tumors (three gastric cancers, one breast cancer, one gall bladder cancer, one liposarcoma and one esophageal cancer), although three tumors (one gastric cancer, one gall bladder cancer, and one colon cancer) exhibited antagonistic effects.
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PMID:[In vitro phase II-III study by clonogenic assay: the combined effects of mitomycin C with alpha-interferon]. 308 90

A specific DNA probe was used to study the effect of recombinant rat, mouse, and human gamma-interferon (gamma-IFN) on the course of sporozoite-induced malaria infections. In mice and rats infected with sporozoites of Plasmodium berghei, mouse and rat gamma-IFN's strongly inhibited the development of the exoerythrocytic forms in the liver liver cells of the hosts, but not the development of the erythrocytic stages. The degree of inhibition of the exoerythrocytic forms was proportional to the dose of gamma-IFN administered, but was independent of the number of sporozoites used for challenge. A 30 percent reduction in the development of exoerythrocytic forms in rat liver was achieved when 150 units (about 15 nanograms of protein) of rat gamma-IFN were injected a few hours before sporozoite challenge; the reduction was 90 percent or more with higher doses of gamma-IFN. The effect was less pronounced if the gamma-IFN was administered 18 hours before or a few hours after challenge. Human gamma-IFN also diminished the parasitemia in chimpanzees infected with sporozoites of the human malaria parasite Plasmodium vivax. The target of gamma-IFN activity may be the infected hepatocytes themselves, as shown by in vitro experiments in which small doses of the human lymphokine inhibited the development of exoerythrocytic forms of Plasmodium berghei in a human hepatoma cell line. These results suggest that immunologically induced interferon may be involved in controlling malaria infection under natural conditions.
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PMID:Inhibition of development of exoerythrocytic forms of malaria parasites by gamma-interferon. 308 18

In the present study we investigated some of the physicochemical properties of macrophage-activating factor(s) (MAF) produced by the tumor-immune Lyt-1+2- T cell subset. Supernatant from mixed culture of spleen and lymph node cells, obtained from C3H/HeN mice immunized with syngeneic MH134 hepatoma or MCH-1-A1 fibrosarcoma, with the corresponding tumor cells exhibited the capability of activating peritoneal exudate macrophages to exert their cytostatic and cytolytic activities on tumor cells. Such MAF production was abolished by treatment of tumor-immune spleen and lymph node cells with anti-Thy-1.2 or anti-Lyt-1.1 antibody plus complement (C) before culturing. Anti-Lyt-2.1 and/or anti-asialo GM1 plus C treatment, however, had only marginal effect on the generation of MAF by these cells, despite the complete disappearance of natural killer (NK) cell activity of spleen and lymph node cells after the treatment with anti-asialo GM1 plus C. Thus, the tumor-specific Lyt-1+2- T cell subset could fulfill a crucial role in generating MAF without the support of NK cells. The MAF activity was heat, acid, and trypsin sensitive. On Sephacryl S-300 column, MAF activity was eluated in a broad single peak around a molecular weight (m.w.) of 70,000 daltons. Antiviral activity was detected in the concentrated pool of MAF-containing fractions from Sephacryl S-300. Gel permeation analysis using HPLC also showed a coincident peak of MAF and antiviral activities at a m.w. of approximately 70,000 daltons. In addition, MAF activity was almost completely neutralized by incubation with rabbit antiserum against recombinant murine gamma-interferon (IFN gamma). Taken together, these results indicate that MAF generated by tumor-immune Lyt-1+2- T cell subset is closely related to IFN gamma.
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PMID:Studies on macrophage-activating factor (MAF) in antitumor immune responses. II. Molecular characterization of MAF produced by the tumor-immune Lyt-1+2- T cell subset. 311 13


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