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 effect of serum from patients with cirrhosis and hepatocellular carcinoma on the release of prostaglandin E2 by the human histiocytic lymphoma cell line U937 was investigated to explain the mechanism underlying the immunoregulatory dysfunction of monocytes in cirrhosis and hepatocellular carcinoma. Prostaglandin E2 production by U937 cells cultured with serum from cirrhosis patients (5.9 +/- 2.7 ng/ml, p less than 0.01) and hepatocellular carcinoma patients (5.4 +/- 2.6 ng/ml, p less than 0.01) was significantly higher than that of control cultures (2.0 +/- 1.0 ng/ml). This activity was decreased after heating and after freezing and thawing. By size exclusion fast protein liquid chromatography, the probable factor was eluted in the fraction with a molecular weight of 150 kD. By anion exchange chromatography with a stepwise increase of the NaCl concentration, the peak activity augmenting prostaglandin E2 production by U937 cells was eluted in the 0.05 to 0.1 mol/L NaCl fraction. The high level of this factor (monocyte-regulating factor) in patient serum might be one cause of abnormal monocyte immunoregulatory function in cirrhosis and hepatocellular carcinoma.
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PMID:Serum factor from patients with cirrhosis and hepatocellular carcinoma enhances production of prostaglandin E2 by U937 cells. 166 19

In order to investigate the production of PGE2 and its' function in human hepatocellular carcinoma, the effects of indomethacin and PGE2 on tumor growth were examined using in vivo and in vitro techniques. HH2-6 cells produced PGE2 in the culture media, and the inverse relationship was observed in between the cell proliferation and the culture supernatant PGE2 levels. While in vivo, plasma and tumor tissue PGE2 levels of tumor bearing nude mice were significantly increased for 1 or 2 weeks after tumor inoculation. In the case of which indomethacin was injected daily into the abdominal cavity (4 mg/kg body weight), the elevation of plasma and tissue PGE2 levels was remarkably suppressed, and the latent time of tumor growth was also prolonged. On the other hand, another case of which PGE2 was injected (10 micrograms or 0.1 microgram i.p.) at first 10 days revealed shortened latent time. These results indicate the intimate relation between PGE2 and latent time on tumor growth. Furthermore, histological findings suggest that tumor derived PGE2 might play an important role in tumor angiogenesis.
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PMID:[In vivo and in vitro studies on PGE2 production and function in human hepatocellular carcinoma]. 254 95

Two rat tumors, Morris hepatoma 7777 (MH) and Yoshida ascites hepatoma AH130 (YAH) were compared, and the influence of systemic inhibition of prostaglandin (PG) synthesis on muscle protein metabolism was evaluated. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats were also treated with naproxen, an inhibitor of PG synthesis. Tumors caused progressive anorexia and weight loss and resulted in decreased weight and/or protein content of the soleus, extensor digitorum longus, and epitrochlearis muscles. The extent of this wasting varied with muscle and tumor type. Muscle wasting induced by the tumors appeared to result from increased protein degradation and/or decreased protein synthesis, as determined in isolated epitrochlearis muscle. In YAH, reduced feed intake did not appear to be responsible for muscle wasting; however, in MH, it accounted for a significant proportion of the muscle loss. YAH produced large amounts of PGE2. Treatment of rats with naproxen inhibited tumor PGE2 production and muscle protein loss in rats bearing YAH. Naproxen had no effect on muscle weight or protein degradation in rats bearing MH. These results would appear to implicate PGE2 in the development of cachexia in the laboratory rat.
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PMID:Effects of systemic inhibition of prostaglandin production on protein metabolism in tumor-bearing rats. 239 72

Several studies have found high cAMP content in hepatomas in vivo, while hepatoma cells in vitro have very low levels. To explore this discrepancy and the regulation of cAMP in hepatomas, we have examined the cell line MH1C1 from Morris hepatoma 7795. These cells in culture contained low intracellular cAMP concentrations (approximately 0.5 pmol/mg protein at confluency), and were unresponsive to glucagon and prostaglandins (PG) E1 and E2. In contrast, solid hepatomas in rats developed from inoculates of MH1C1 had a 40-fold higher basal cAMP concentration and were stimulated by PGE1 and PGE2. Fibroblasts cultured from these tumours also contained high cAMP levels and responded strongly to PGE1. This may suggest that the difference in cAMP regulation between hepatomas in vivo and hepatoma cells in vitro results from the presence of other cells in the solid tumour rather than from selection of low-cAMP cells during the cloning procedure. Low-Km and intermediate-Km cAMP phosphodiesterase activity was high in MH1C1, compared to normal hepatocytes. This might contribute to the low cAMP level. The ability of MH1C1 to form cAMP was not defective, as the level could be increased more than 200-fold by beta-adrenergic activation in the presence of the phosphodiesterase inhibitor methylisobutylxanthine.
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PMID:The regulation of cyclic AMP levels in cultured MH1C1 rat hepatoma cells and in solid tumours derived from MH1C1 cell inoculates. 303 96

By fusion of C3H/HeJ splenic adherent mononuclear cells enriched for macrophages with HPRT-deficient C57L/J HH- hepatoma cells, we have generated six macrophage-hepatoma hybrid clones. The hybrid nature of isolated clones was demonstrated by karyotypic analysis. The hybrid clones were screened for macrophage properties by assaying the presence of two enzymes: nonspecific esterase and lysozyme. Three of six hybrids expressed higher amount of Ia antigen and less amount of FcR; the other three hybrids expressed higher amounts of Fcr, but no Ia antigen. Phagocytosis of serum-opsonized beads is positively correlated with FcR expression, while the proliferation of antigen-primed lymphocytes is only induced by antigen-pulsed hybrids expressing Ia antigen. One hybrid clone (MH3-1) secreted significantly higher level of PGE2 and also expressed Ia antigen with higher ability of antigen-presentation. The data suggest that the cell hybridization can segregate macrophage-featured phenotypes into different hybrid clones which perform distinct functions. It may facilitate the study on the relationship of macrophage functions and the relationship between the functions and defined cell structure.
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PMID:Generation of phenotypically distinct macrophage-hepatoma hybrid clones. 347 90

Prostaglandin (PG) E2 biosynthesis in Yoshida hepatoma (AH 130) was evaluated by radioimmunoassay. When hepatoma cells were incubated in vitro, the levels of PGE2 in the medium were similar to those found in hepatocytes for the first 2 h; this was followed by a rapid increase in PGE2 formation, and the 6h incubation levels were 4-fold higher than in hepatocytes. Addition of sodium arachidonate markedly and dose-dependently stimulated PGE2 synthesis; the increase was largely prevented by the addition of indomethacin (1 microM) or L 8027, a prostaglandin synthetase inhibitor. Experiments in vivo indicated that indomethacin treatment of tumour-bearing rats significantly reduced the tumour mass. When rats were injected with PGE2 after receiving the drug, the number of tumour cells was very similar to that of untreated animals. This, as well as the inhibition of tumour growth by acetylsalicylic acid, strongly suggests that the inhibition of PG biosynthesis by anti-inflammatory drugs and the inhibition of tumour proliferation may be closely associated events. It was also found that injections of indomethacin very significantly prolonged survival of hepatoma-bearing rats. Since PGE2 does not appear to affect the cyclic AMP levels of hepatoma cells, it is possible that hepatoma may use PGE2 to subvert the immune system. This could help to explain the effectiveness of anti-inflammatory drugs in the control of tumour growth.
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PMID:Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumour growth by non-steroidal anti-inflammatory drugs. 624 92

Serum amyloid A (SAA) protein is a major acute phase reactant in human and many other species. Infections and traumatic inflammation are characterized by a rapid increase of SAA; its concentration in the plasma may augment many-fold. Cytokines such as IL-1 and IL-6 are considered mediators of acute phase protein synthesis. The most accredited mechanism of action of IL-1 in inflammatory diseases is the stimulation of PGE2 release, which is highly dependent on the concentration of IL-1. In this study we found that human Hep 3B hepatoma cells treated with the combination of hrIL-6 (10ng/ml) plus hrIL-1 (1ng/ml) produced an augmentation in steady-state levels of SAA mRNA (87%) compared to hrIL-6 (10ng/ml) plus PGE2 (5 microM), which induced an increase of only 33%, compared to IL-6 alone, while cells treated with hrIL-6 plus PGE2 (0.5 microM) had a similar effect as hrIL-6 did alone. Moreover, the addition of exogenous PGE2 (5 microM) to the cell cultures produced no significant increase in concentration of SAA mRNA compared to the control. In addition, according to the data obtained by the blot analysis we also found, by ELISA method, that hrIL-6 acts in synergism with hrIL-1 on SAA protein secretion in human Hep 3B hepatoma cell cultures after 48 h incubation. In fact, the cell cultures treated with hrIL-6 plus hrIL-1 caused a higher release approximately 1.5-4-fold of SAA protein than the cells treated with IL-6 plus PGE2 5 microM or IL-1 + PGE2 5 microM, respectively. The synergistic effect of hrIL-6 plus hrIL-1 beta was inhibited by hrIL-1 receptor antagonist (hrIL-1ra) 50 micrograms/ml, a protein which specifically binds to the IL-1 receptor and is structurally similar to IL-1 beta but with no IL-1-like activity; while indomethacin (5 microM) was ineffective. These results strongly suggest that the synergism between hrIL-6 plus hrIL-1 on the transcription and the protein release of SAA release is not due to a PGE2-dependent process in human Hep 3B hepatoma cells. This finding highlights a specific biological effect of IL-1 not in relation to PGE2, suggesting a specific mechanism of action for IL-1 in regulating acute phase protein synthesis.
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PMID:Synergistic activation of serum amyloid A (SAA) by IL-6 and IL-1 in combination on human Hep 3B hepatoma cell line. Role of PGE2 and IL-1 receptor antagonist. 779 46

The PGE2 concentration of sera and tumor tissues in human hepatocellular carcinoma (hHCC) xenografts in nude mice was examined by radio-immuno-assay (RIA) and the effect of intraperitoneal administration of exogenous of PGE2 as well as indomethacin on tumor growth was studied. The results showed that: (1) Plasma and tumor tissue PGE2 levels of hHCC-bearing nude mice were significantly increased for 1 or 2 weeks after tumor inoculation. (2) Exogenous administration of indomethacin markedly suppressed the elevation of plasma and tissue PGE2 levels and prolonged the latent period of tumor growth. (3) Exogenous PGE2 shortened the latent period of tumor growth. This study indicates that there is intimate relation between PGE2 and hHCC growth.
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PMID:[In vivo studies on PGE2 production by human hepatocellular carcinoma xenografts in nude mice]. 826 62

In order to study the mechanism of cancer metastasis, AH100B cells, an ascitic hepatoma cell line, were transplanted into the small intestine of male Donryu rats. Each metastatic nodule in the liver was collected with the respective intestinal lesion. Each sample thus obtained was injected into the peritoneal cavity of male Donryu rats to make free cancer cells. Then, the cancer cells, having an intact cell surface, of the metastatic and primary intestinal lesion were collected respectively. After washing in Dolbecco's PBS (Ca2+ and Mg(2+)-free, pH 7.2), the definite numbers of cancer cells of the metastatic and primary intestinal lesion were incubated in the PBS containing [1-14C]-AA at 25 degrees C for 30 min, respectively. AA metabolites formed during the incubation period were extracted and subjected to TLC, followed by autoradiography. Each radioactive part was scraped off the plate and measured for its radioactivity. The pattern of the ability to synthesize PGs was different between the cancer cells which metastasized to the liver and those of the primary lesion, that is, percentage values of PGE2 and PGF2 alpha were higher (p < 0.01) in the cancer cells which metastasized to liver as compared with those of the primary intestinal lesion. These results suggest that PGs produced by hepatic metastatic cancer cells might play an important role in cancer metastasis.
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PMID:Some features in prostaglandin synthesis of the cancer cells which metastasized into liver from intestinal cancer lesions. 826 26

In order to study the mechanism of cancer metastasis, AH100B rat hepatoma cells were transplanted to the stomach of male Donryu rats. Each hepatic metastatic nodule was collected with the respective primary gastric lesions. Each sample thus obtained was injected separately into the peritoneal cavity of male Donryu rats to make free cancer cells; then, intact cancer cells of the hepatic metastatic and primary gastric lesions were collected. After washing in Dulbecco's phosphate-buffered saline (Ca2+ and Mg(2+)-free, pH 7.2), the definite number of the metastatic and primary gastric cancer cells were incubated in the phosphate-buffered saline containing [1-14C] arachidonic acid at 25 degrees C for 30 min. Arachidonic acid metabolites formed during the incubation period were extracted and subjected to thin-layer chromatography, followed by autoradiography. Each radioactive spot was scraped off the plate and measured for its radioactivity. The pattern of the ability to produce PGs was different between the cancer cells which metastasized to the liver and those of the primary lesions, that is, percentage of PGF2 alpha was higher (p < 0.05) and that of PGE2 was quite higher (p < 0.01) in the hepatic metastatic cancer cells as compared with those of the primary gastric lesion. These results suggest that PGs produced by hepatic metastatic cancer cells might play an important role in hepatic metastatic formation.
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PMID:Some features of prostaglandin synthesis of the cancer cells metastasized into liver from gastric cancer lesions. 827 90


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