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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of human cancers, a renal cell carcinoma and a hepatocellular carcinoma, were investigated in vitro; both produced a marked erythrocytosis in each patient. These tumors, when transplanted into athymic nude mice, produced a remarkable erythrocytosis in the host mice. To analyze this phenomenon, the primary cultures from these xenotransplanted tumors were performed. To obtain pure tumor cell cultures, cells derived from host nude mice were eliminated by the treatment with the antiserum raised against nude mouse cells. Epithelial cells derived from each tumor attached and grew in the cultures. The conditioned media from both tumor cells revealed high erythropoietic stimulatory activities. We have characterized these erythropoietin-like activities by size-exclusion high-performance liquid chromatography. Three peaks of erythropoietin-like activities were noted after bovine serum albumin region. The molecular weights were estimated at about 55,000, 40,000, and 33,000, respectively. The results suggested that the human renal cell and hepatocellular carcinomas produced erythropoietin-like activities in vitro in culture and that erythrocytosis found in patients with cancer and in nude mice transplanted with the tumors was attributable to production of the erythropoietin-like activities by the tumor cells themselves.
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PMID:Production of erythropoietin-like activity by human renal and hepatic carcinomas in cell culture. 403 14

Primary hepatoma was found in a 38-year-old female who had been using an oral contraceptive for 28 months. Histologically the hepatoma was a well-differentiated hepatocellular carcinoma. Alpha-fetoprotein was not increased and tests for HBS antigen was negative. Carcinoembryonic antigen was elevated remarkably before death. The findings of hepatic arteriography and peritoneoscopy suggested metastatic tumors of the liver rather than primary hepatoma. During the course of the disease, phlebothrombosis occurred and spread widely in the lower left limb. The observation of erythrocytosis indicated the presence of a tumor producing erythropoietin or an erythropoietin-like substance.
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PMID:An autopsy case of primary hepatoma associated with an oral contraceptive. 629 50

Erythrocytosis was seen in two men during maintenance hemodialysis therapy for end-stage renal disease secondary to apparent chronic glomerulonephritis. Nonrenal causes of erythrocytosis such as polycythemia vera, chronic hypoxemia, high-oxygen affinity hemoglobin, and hepatoma were excluded by appropriate clinical studies. A computed tomographic scan of the abdomen showed numerous renal cysts in each patient consistent with acquired cystic disease of end-stage kidneys. Peripheral serum erythropoietin levels were elevated as measured by sensitive radioimmunoassay. The findings suggest that the erythrocytosis is caused by an erythropoietic mechanism related to the diseased kidneys. A review of the literature failed to show previous reports of this clinical association.
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PMID:Erythrocytosis in patients on long-term hemodialysis. 713 32

Transcriptional regulation of gene expression by hypoxia is an important, but yet only marginally characterized mechanism by which organisms adapt to low oxygen concentrations. The human hepatoma cell line HepG2 is a widely used model for studying hypoxic induction of the hematopoietic growth factor erythropoietin. In an attempt to identify additional genes expressed in HepG2 cells during hypoxia, we differentially screened a cDNA library derived from hypoxic (1% O2) HepG2 cells using probes isolated from either normoxic (21% O2) or hypoxic cells. Two genes were identified, one encoding aldolase, a member of the glycolytic enzymes, and the other encoding alpha 1-antitrypsin which belongs to the family of the acute phase (AP) responsive proteins. Whereas hypoxic induction of glycolytic enzymes is well established, oxygen-dependent regulation of AP genes has not been reported so far. AP proteins are liver-derived plasma proteins whose production during inflammation is either up-regulated (positive AP reactants) or down-regulated (negative AP reactants). In the present study, we demonstrate that on the mRNA level hypoxic stimulation of HepG2 cells led to (i) an induction of the positive AP reactants alpha 1-antitrypsin, alpha 1-antichymotrypsin, complement C3, haptoglobin, and alpha 1-acid glycoprotein; (ii) a down-regulation of the negative AP reactant albumin; (iii) an up-regulation of the negative AP reactant transferrin; and (iv) unchanged levels of the positive AP reactants alpha- and beta-fibrinogen as well as hemopexin. Cycloheximide inhibited hypoxic up-regulation of AP mRNAs demonstrating that de novo protein synthesis is required for hypoxic induction. Nuclear run-on assays indicate that the hypoxic increase in AP mRNAs is mainly due to transcriptional regulation. The hypoxic response was compared to AP stimulation by interleukin 6. The results suggest that the adaptive response to hypoxia overlaps with, but is not identical with, the AP response mediated by interleukin 6.
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PMID:Hypoxia, a novel inducer of acute phase gene expression in a human hepatoma cell line. 749 59

This study investigates the effects of hypoxia and of cobalt on erythropoietin (EPO) gene expression in hepatocytes in vivo and in vitro in neonatal, juvenile, and adult rats. With the use of the ribonuclease protection assay to quantify RNA, both hypoxia (0.1% CO or 9% O2) and cobalt (60 mg/kg) elicit production of increased amounts of EPO mRNA in neonatal and juvenile rat liver in vivo. In vitro hepatocyte EPO gene expression could be reproducibly stimulated by hypoxia (3% O2) but not by cobaltous chloride (50-150 microM) within 2-20 h. Conversely, cobalt substantially attenuated the rise of EPO mRNA levels in response to hypoxia. This inhibitory effect of cobalt was mimicked by zinc but not by other metals. CO attenuated the rise of EPO mRNA levels in vitro in response to hypoxia; this inhibitory effect coincided with an inhibition of total RNA synthesis as determined by [3H]uridine incorporation. The lack of specific inhibitory effects of CO and of specific stimulatory effects of cobalt on hepatocyte EPO gene expression in vitro suggests that a specific heme oxygen sensor may be less important than in hepatoma cells.
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PMID:Cobalt exerts opposite effects on erythropoietin gene expression in rat hepatocytes in vivo and in vitro. 750 28

Effects of thyroid hormones on the production of erythropoietin (Epo) were investigated in isolated perfused rat kidneys and in the human hepatoma cell line, HepG2. Epo protein was measured by radioimmunoassay. L-triiodothyronine and L-thyroxine stimulated hypoxia-induced Epo formation both in the kidney and in HepG2 cells in a dose-dependent fashion. Quantitation of Epo mRNA by competitive polymerase chain reaction (PCR) showed that hypoxic HepG2 cells had three-fold higher Epo messenger RNA levels when treated with thyroid hormones for 3 hours. Measurements of oxygen consumption revealed that this effect was not due to an increase in the degree of hypoxia. Thus, apart from the known direct effect on erythroid precursors, thyroid hormones appear to stimulate erythropoiesis by a noncalorigenic increase in Epo production.
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PMID:Thyroid hormones enhance hypoxia-induced erythropoietin production in vitro. 750 90

A 68-year-old man with hepatocellular carcinoma complicated by erythrocytosis showed an increased plasma level of immunoreactive erythropoietin (EPO). Northern blot analysis and RT-PCR (reverse transcriptase and polymerase chain reaction) of EPO mRNA extracted from a surgical specimen indicated high expression of EPO mRNA in the tumor tissue. Histological and immunocytochemical examination showed that the tumor was a hepatocellular carcinoma with predominant immunostaining for EPO. The erythrocytosis improved and the high serum EPO level decreased after resection of the tumor. This is the first demonstration of EPO mRNA expression in hepatocellular carcinoma tissue by RT-PCR.
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PMID:Gene expression of erythropoietin in hepatocellular carcinoma. 752 23

Hypoxia-induced erythropoietin (Epo) production in vitro is suppressed by interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF) and phorbol esters. Herein, the Epo-synthesizing human hepatoma cell line HepG2 was used to investigate whether protein kinase C (PKC) is involved in the inhibitory action of the cytokines. Within 1 h after the onset of hypoxia, Epo mRNA levels were markedly increased in untreated HepG2 cells as quantitated by competitive reverse transcription PCR. The cytokines IL-1 beta and TNF prevented this hypoxia-induced increase in Epo mRNA levels. In phorbol-ester-treated cells first inhibitory effects on Epo mRNA levels were observed only after 3 h. Western blot analyses revealed the presence of four isoenzymes of PKC in HepG2 cells. None of these isoenzymes was translocated in response to TNF or IL-1 beta, suggesting that the cytokines do not activate PKC in HepG2 cells. In contrast, phorbol esters translocated and, upon prolonged exposure, down-regulated PKC isoenzymes alpha and epsilon. Activation of protein kinase A by dibutyryl-cAMP partially antagonized the cytokine-dependent inhibition of Epo production but did not influence the inhibitory effect of phorbol esters. Endogenous cAMP levels in HepG2 cells were unchanged by cytokine treatment. Obviously, at least two signaling pathways exist that can confer inhibition of Epo production in HepG2 cells. One of these may be mediated by down-regulation of the PKC alpha or epsilon isoenzyme. The other pathway, however, which is triggered by IL-1 beta and TNF, is independent of PKC.
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PMID:Distinct signaling pathways mediate phorbol-ester-induced and cytokine-induced inhibition of erythropoietin gene expression. 752 38

The precise cause of the anaemia that is commonly associated with severe pulmonary tuberculosis (PTB) has not been elucidated. The role of erythropoietin (Epo), the central hormone regulating red cell formation, still awaits clarification. We therefore determined serum Epo levels in patients with PTB; group 1, haemoglobin less than 110 g/L, group 2, haemoglobin greater than 110 g/L; group 3, controls, consisted of matched individuals with uncomplicated iron deficiency; group 4, healthy volunteers. Peripheral blood monocytes were obtained from patients with PTB and the controls, cultured, and the supernatant fluid (SNF) harvested. Tumour necrosis factor alpha (TNF alpha) levels were determined in the SNF, which were then added in various dilutions to a hepatocellular carcinoma cell line (HepG2) capable of regulated EPO synthesis in vitro. The influence of this cytokine was defined by the addition of specific neutralising anti-TNF alpha antibodies in this assay system. Patients in group 1 had significantly lower Epo levels (54 + 11 mU/mL) compared with those in group 3 (142 +/- 41 mU/mL) (p < 0.01). Monocyte supernatants from patients in the anaemic PTB group had markedly elevated TNF alpha levels and significantly suppressed Epo output by HepG2 cells in vitro (p < 0.01). This inhibition was consistently abrogated by anti-TNF alpha antibodies. Serum Epo levels were inappropriately low in untreated PTB patients when compared with corresponding haemoglobin levels in iron deficient controls. This blunted response could be ascribed to release of TNF alpha or other cytokines by activated monocytes.
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PMID:Blunted erythropoietin response to anaemia in tuberculosis. 758 43

It has been shown previously that erythropoietin expression in vitro by hepatoma cells increases in response to hypoxia. To verify whether hypoxia of the tumor might result in hepatic release of erythropoietin in vivo, serum erythropoietin concentrations were measured immunoenzymatically in 12 patients (5 women, 7 men) who underwent transarterial chemoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in three male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization of the hepatic veins and of the right antecubital vein. None of the patients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 micrograms/L, serum erythropoietin concentrations were the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t-test). The ratio of hepatic vein/antecubital vein serum erythropoietin concentrations increased from 0.85 at baseline to 1.30 at +2 days, paralleling the increase of aspartate transaminase (r = .914, P < .005). After chemoembolization, no correlation was found between serum erythropoietin and alpha-1-fetoprotein concentrations. The concentration of the latter, stable initially, decreased 7 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic release of erythropoietin induced by transarterial chemoembolization in patients with hepatocellular carcinoma. 760 7


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