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)

The effects of several immunomodulatory peptides (recombinant, human) on the in vitro production of erythropoietin (Epo) were studied in cultures of the human hepatoma cell line Hep G2. A dose-dependent decrease of up to 60% in Epo production was induced by interleukin-1 beta, interleukin-1 alpha, and tumor necrosis factor-alpha (in that order of potency). In contrast, moderately increased Epo levels resulted with interleukin-6 or interferon-gamma treatment at high concentrations. Concomitant measurements of the production of alpha-fetoprotein indicated that the observed effects were specific for Epo. Hence, we suspect a modulating role of the immune system in the in vivo control of Epo production and postulate that interleukin-1 and tumor necrosis factor-alpha are involved in some of the cases of lowered blood Epo levels in association with renal diseases, chronic inflammation, and malignancies.
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PMID:Interleukin-1 and tumor necrosis factor-alpha inhibit erythropoietin production in vitro. 171 53

Two days exposure to recombinant tumor necrosis factor (rTNF-alpha) produced a dose-dependent reduction in (methyl-3H) thymidine incorporation in RC-3 cells (ID50 = 25 units/ml). Prolonged treatment with rTNF-alpha further resulted in a significant reduction in colony formation (ID50 = 200 units/ml), which was reversed upon removal of the agent. Interferon levels were undetectable in the supernatants of the rTNF-alpha treated cells. Simultaneous exposure to dexamethasone prevented the growth inhibition in rTNF-alpha-treated RC-3 cells. Significant dose-dependent increase in the steady state levels of the mRNA for multidrug resistance (MDR1) gene was observed after rTNF-alpha treatment while simultaneous exposure to dexamethasone produced a substantial reduction in the mRNA levels for MDR1 gene. These data suggest that growth inhibitory effects of TNF are regulated by dexamethasone and are associated with changes in MDR1 mRNA levels in hepatoma-derived cells.
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PMID:Dexamethasone prevents the growth inhibitory effects of recombinant tumor necrosis factor in a rat hepatoma cell line Reuber-RC-3: an association with the changes in the messenger RNA levels for multidrug resistance gene. 172 6

A case of unresectable hepatocellular carcinoma which responded favorably to combined therapy with tumor necrosis factor (TNF) and local hyperthermia is reported. A 58-year-old man was admitted to our hospital in June 1988 for treatment of hepatocellular carcinoma affecting S4 and S8. After three sessions of transcatheter arterial embolization (TAE) therapy, the serum alpha 1-fetoprotein level decreased, and a reduction in the size of the lesions was also noted. Thereafter, the patient received local hyperthermia once a week (60 minutes of irradiation from a Thermotron-RF8 at 1,100W), but the alpha 1-fetoprotein level increased again in February 1989. On examination, enlargement of the S8 lesion and a new nodule in S7 were recognized. Since TAE was contraindicated due to liver dysfunction, human recombinant TNF (1 x 10(6)U) was given by intravenous infusion together with local hyperthermia once a week. Eight sessions of the combined therapy reduced the serum alpha 1-fetoprotein level markedly (7,512.0 to 2,782.0 pg/ml) and after eighteen sessions, 58.1% regression of tumor size (partial response) on computed tomography scans was observed. This anecdotal case supports previous experimental evidence suggesting that TNF plus hyperthermia may be effective for treating unresectable hepatocellular carcinoma.
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PMID:Successful treatment of a case of hepatocellular carcinoma with tumor necrosis factor and local hyperthermia. 172 71

Nicotinamide methyltransferase (Nmd CH3transferase) activity increased in the liver of mice after i.p. transplantation of Ehrlich ascites tumor (ascitic form), but not in the liver of mice with acute inflammation induced by the i.p. administration of D-galactosamine, and it rather showed a decrease together with necrosis after carbon tetrachloride administration. When Nmd CH3transferase activity of rat hepatocytes in primary culture was investigated with the addition of dexamethasone, epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha and N1-methylnicotinamide (1-CH3Nmd), changes in activity were not correlated with DNA synthesis, suggesting that the increase of this enzyme activity in the tumor host liver was not directly related to liver cell proliferation. Thus, in order to make use of the increase of this enzyme activity as a tumor burden marker, a procedure for its estimation by measuring the blood level of 1-CH3Nmd, a metabolite of Nmd produced by Nmd CH3transferase, was established. The 1-CH3Nmd level in the blood of mice bearing Ehrlich ascites tumor 4 h after s.c. loading of Nmd (500 mg/kg body weight) was closely correlated with this enzyme activity in the liver (r = 0.835, P less than 0.00001) from the early to the terminal stage of tumor development. Furthermore, similar correlations were seen in the animal groups bearing various other tumors, such as s.c. implanted Ehrlich ascites tumor (solid form) and i.p. implanted sarcoma S-180, hepatoma MH-134, Yoshida ascites sarcoma and leukemia L-1210, but not solid tumors such as Lewis lung carcinoma and melanoma B-16, although almost all of the animals bearing these tumors showed a higher enzyme activity than their control normal animals.
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PMID:N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden. 183 57

Serum levels of phospholipase A2 (PLA2) activity have been shown to be elevated in cases of septic shock and rheumatoid arthritis. The cellular origin of serum PLA2, however, is not known. In this report, we demonstrate that human group II PLA2 expression and secretion are induced in hepatoma cells (HepG2) following treatment with interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-1 (IL-1). Of the three cytokines, IL-6 is the most potent. Significant synergy is observed between IL-6 and IL-1 and between IL-6 and TNF, but not between IL-1 and TNF. PLA2 induction does not occur in human YT cells, which are known to have receptors for both IL-1 and IL-6, indicating that the regulatory mechanism involved is cell type-specific. The results of RNA blot analysis indicate that the PLA2 gene is regulated in HepG2 cells at the pretranslational level. Induction of PLA2 synthesis in HepG2 cells in response to these cytokines resembles the induction of the acute phase plasma proteins which are synthesized in cultured hepatocytes and hepatoma cells following exposure to the same cytokines and in liver in response to inflammation and infection. In addition, a putative IL-6-responsive element, which is homologous to a similar element found in several acute phase genes, is present in the 5'-promoter-proximal region of the PLA2 gene. These results suggest that serum PLA2 is synthesized in and secreted from liver cells in response to inflammatory stimuli, mediated primarily by IL-6, and therefore should be classified as an acute phase protein.
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PMID:Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. 184 31

We have shown the in vivo usefulness of a novel chimera tumor necrosis factor (TNF), called rTNF-STH, which was constituted with human thymosin beta 4 and recombinant human TNF-SAM1. Tumor necrosis was induced by intravenous injection of a smaller amount of rTNF-STH (1 x 10(3) U/mouse, 0.67 microgram/mouse) than rTNF-alpha or rTNF-S (1 x 10(4) U/mouse, 2.5-5 micrograms/mouse). Significant antitumor effects of rTNF-STH to Meth A fibrosarcoma, B16 melanoma, MH134 hepatoma, or Lewis lung carcinoma (3LL) were observed by systemic injection of rTNF-STH at the maximum tolerable dose of 1 x 10(4) U/mouse (6.7 micrograms/mouse); this dose did not cause regression of tumors by conventional rTNF-alpha. rTNF-STH showed a significant prolongation of its half-life in serum. The average calculated half-life of the chimera protein is about 110 min, which is 15 times longer than that of original TNF-SAM1 (7.5 min). On the basis of this prolongation of half-life of rTNF-STH and its efficient hemorrhagic necrotic activity, the antitumor effect of rTNF-STH--as compared with that of the known TNF species--is discussed. Findings indicate that use of the chimera protein to alter the N-terminal region of TNF may be a promising approach to obtain molecules that more favorably attack tumors and other diseases than conventional rTNFs.
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PMID:Antitumor activity of a novel chimera tumor necrosis factor (TNF-STH) constructed by connecting rTNF-S with thymosin beta 4 against murine syngeneic tumors. 204 90

The mRNAs of transiently expressed cytokine genes contain AUUUA-rich sequences in the 3' untranslated regions. In order to examine whether the AU-specific endoribonuclease V (EC 3.1.27.8) described previously by us transinactivates those mRNA species, we introduced a 51-nucleotide ATTTA sequence from tumor necrosis factor into the 3' untranslated region of beta-globin gene. Transcripts of that construct, synthesized in vitro, were prone to endoribonuclease V digestion at those AU-rich sequences. Stimulation of human macrophages with lipopolysaccharide resulted in a shift of the association state of the enzyme from the nuclear matrix-associated to the free form. This shift was strongly prevented by the hepatitis B surface antigen (HBsAg) and more weakly by hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region. HBsAg and, to a lesser extent, hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region inhibited the release of alpha interferon, tumor necrosis factor alpha, and granulocyte-macrophage colony stimulating factor, while it had no effect on interleukin-1 production from stimulated macrophages. Using the human hepatoma cell line PLC/PRF/5, we provide further experimental evidence that endoribonuclease V acts in trans as a posttranscriptional inactivator for nuclear matrix-associated cytokine transcripts. These results suggest that those cytokine transcripts which contain reiterated (overlapping) AUUUA sequences are degraded by nuclear matrix-associated endoribonuclease V. This degradation was comparably high in cells incubated with HBsAg or cells which produced this antigen.
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PMID:Immunosuppressive function of hepatitis B antigens in vitro: role of endoribonuclease V as one potential trans inactivator for cytokines in macrophages and human hepatoma cells. 215 63

In order to investigate the effect of tumor necrosis factor (recombinant TNF-alpha) on hepatoma, we assessed the antitumor activity of TNF-alpha on hepatoma cell line, PLC/PRF/5 in vitro, and combined effects of interferon-gamma (IFN-gamma), that is thought to increase TNF-receptors. TNF-receptors. TNF-alpha for itself, had no significant effect on DNA synthesis and viability, and the production of HBsAg from PLC/PRF/5. On the other hand, treatment of IFN-gamma- combined with TNF-alpha inhibited DNA synthesis and production of HBsAg. The decrease of viability of PLC/PRF/5 was also found in this combination treatment. According to these findings, antitumor activity of TNF-alpha had no effect on PLC/PRF/5 in itself, but was significantly enhanced when treated with IFN-gamma at the same time.
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PMID:[A basic study of cytotoxic effect of tumor necrosis factor-alpha on the hepatoma cell line, PLC/PRF/5]. 215 10

The monokine, cachectin/tumor necrosis factor (TNF) differs from interleukin 1 (IL-1) in primary structure and in recognition by a distinct cellular receptor. It does, however, encode effector functions that are similar to those of IL-1 and characteristic of the host response to inflammation or tissue injury. Accordingly, we examined the possibility that recombinant-generated human TNF regulates hepatic acute-phase gene expression. In picomolar concentrations, TNF mediated reversible, dose- and time-dependent increases in biosynthesis of complement proteins factor B and C3, alpha 1 antichymotrypsin, and decreases in biosynthesis of albumin and transferrin in human hepatoma cell lines (Hep G2, Hep 3B). Biosynthesis of complement proteins C2 and C4, and alpha 1 proteinase inhibitor were not affected by TNF. TNF also increased factor B gene expression, but had no effect on C2 gene expression, in murine fibroblasts transfected with cosmid DNA bearing the human C2 and factor B genes. The effect of TNF on acute-phase protein expression (C3, factor B, albumin) was pre-translational as shown by changes in specific messenger RNA content.
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PMID:Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. 242 91

A subline of the rat hepatoma (H-35) cells has been identified which responds to hepatocyte-stimulating factors (HSFs) of human squamous carcinoma cells by increased synthesis of all major rat acute phase plasma proteins. The regulation occurs at the level of mRNA. Two HSFs (HSF-I and HSF-II) have been purified from conditioned medium of the squamous carcinoma cells. HSF-I is a protein with an Mr = 18,000 and pI 5.5, and HSF-II is a glycoprotein with an Mr = 34,000 and a broad, neutral to basic charge. In H-35 cells, HSF-I predominantly stimulates the synthesis of complement C3 and haptoglobin and acts synergistically with dexamethasone to stimulate alpha 1-acid glycoprotein. HSF-II stimulates cysteine protease inhibitor, alpha 1-antichymotrypsin, alpha 1-antitrypsin, fibrinogen, and hemopexin, and acts synergistically with dexamethasone to stimulate alpha 2-macroglobulin. Each HSF is between 10 and 100 times less effective in regulating proteins of the other set. Human tumor necrosis factor and interleukin-1 increase complement C3, haptoglobin, and alpha 1-acid glycoprotein, as does HSF-I, but are unable to modulate any of the other acute phase proteins. The monokines differ from HSF-I is their low activity in HepG2 cells and rat hepatocytes.
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PMID:Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. 243 11


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