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)

Retarded development of exoerythrocytic stages of the rodent malaria parasite Plasmodium berghei in human hepatoma cells by extracts from Dioncophyllaceae and Ancistrocladaceae species. International Journal for Parasitology 27: 29-32. Naphthylisoquinoline alkaloid-containing extracts (10 micrograms ml-1) of species belonging to the Dioncophyllaceae and the Ancistrocladaceae, 2 small tropical plant families, display pronounced in vitro activities against exoerythrocytic stages of Plasmodium berghei (Anka), developing in human hepatoma cells (Hep G2). The highest activities were obtained with CH2Cl2 root and bark extracts, and a CH2Cl2/NH3 leaf extract from Triphyophyllum peltatum, a CH2Cl2/NH3 root extract from Ancistrocladus abbreviatus, and a CH2Cl2 leaf extract from A. tectorius. The degrees of growth inhibition ranged within 27.7-70.0%. The commercially available drug primaquine diphosphate (25 micrograms ml-1) caused a comparable effect (62.1%) in the same test system.
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PMID:Retarded development of exoerythrocytic stages of the rodent malaria parasite Plasmodium berghei in human hepatoma cells by extracts from Dioncophyllaceae and Ancistrocladaceae species. 907 26

We performed interventional angiography (IVA) in a patient with liver cirrhosis (LC) and hepatoma (HCC) who experienced repeated attacks of unconsciousness due to hyperammonemia caused by ileocecal-inferior vena cava (IC-IVC) shunt and succeeded in the treatment. We report the results below. The patient, 53-year-old male, underwent endoscopic injection sclerotherapy for esophageal varix due to LC followed by splenectomy for pancytopenia in 1986. He made good progress. However intraarterial anticancer therapy was conducted for HCC in 1994. From that time hepatic coma began to appear and its frequency gradually increased. Hepatic coma occurred once every 3 weeks from June 1996. He was thus admitted to our hospital. Hematobiochemical testes showed that ammonia level was 297 mcg/dl. Albumin 2.8d/dl, and Total-Bilirubin 10.78 mg/dl. Arterioportography from superior mesenteric artery showed most of portal blood flowed away from the liver though the ileocolic vein to IVC. We decided to conduct IVA for treatment. Specially, a 6Fr balloon catheter was inserted from the right inguinal region into a shunt to the portal vein though IVC by the Seldinger technique. The balloon was inflated in the shunt to close the shunt. Six ml of 5% ethanolamime oleate with iopamidol was injected because retrograde angiography showed that iopamidol was flowed out via testicular vein to IVC. The balloon catheter was retained for 24 hours. Angiography, conducted from the catheter again 24 hours later, showed that the shunt was occluded, blood ammonia level was 71 mcg/dl after occlusion. Hepatic coma was not observed after treatment. We encountered a very rare case who repeated hepatic comas due to IC-IVC shunt and recovered dramatically after IVA.
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PMID:Hepatic coma recovered after interventional obliteration for ileocecal-inferior vena cava shunt--report of one case. 938 49

A new human myeloma cell line, KMS-18, was established from a 58-year-old male with multiple myeloma associated with hyperammonemia. The original leukemic cells and established KMS-18 cells possessed several of the same chromosomal abnormalities, including add(1)(q32), add(10) (q24) and add(17)(p11). In addition, the KMS-18 cells showed novel t(4;14)(p16.3;q32.3) masked translocation which was determined by the FISH method. Moreover, we compared the ammonia production in culture medium of the KMS-18 cell line with that of non-myeloma hematological malignant cell lines and a hepatocellular carcinoma cell line. KMS-18 produced higher levels of ammonia in medium than the other cell lines examined. This new cell line may prove helpful in analyzing the role and biological mechanisms of the t(4;14)(p16.3;q32.3) translocation in myeloma and also in investigating hyperammonemia in cases with myeloma.
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PMID:Establishment of a new human myeloma cell line, KMS-18, having t(4;14)(p16.3;q32.3) derived from a case phenotypically transformed from Ig A-lambda to BJP-lambda, and associated with hyperammonemia. 947 91

A variant RL-ET-1G of a rat liver epithelial cell line (RL-ET-1) characterized by a very high inducibility for glutamine synthetase (GS) in response to dexamethasone was established by cultivation in glutamine-free, glutamate-supplemented culture medium. Using this cell line, conditioned medium produced by periportal hepatocytes in primary culture was found to suppress this induction, acting with a lag-phase of about 8 h irrespective whether the GS activity was basal or preinduced. Analysis of the response of several epithelial cell lines to the conditioned medium showed a reciprocal relationship between the dexamethasone-dependent induction and the residual activity after exposure to the conditioned medium, indicating that a hypothetical factor in the conditioned medium was interfering with the induction process but not with the basal GS level of these cells. Careful analysis revealed that the effect of the conditioned medium was neither due to deficiency of a component used up by the hepatocytes, nor due to glutamine or ammonia, both of which affected GS activity at concentrations above 0.5 mmol/L. The hypothetical factor was found to be quite small (molecular mass range 100-500 Da), heat and acid stable, as well as highly water soluble. Most interestingly, the conditioned medium did not suppress GS induction in astroglial cells and in the two hepatoma cell lines C2 and FAO, but strongly diminished the spontaneous induction of GS in cocultured pig hepatocytes, suggesting that the hypothetical factor acts primarily on normal nontransformed liver-derived cell populations.
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PMID:Conditioned medium from cultured rat hepatocytes completely blocks induction of glutamine synthetase by dexamethasone in several rat liver epithelial cell lines. 953 46

Cells from primary porcine hepatocytes (PPH) and the immortalized human hepatoma cell line C3A are both used in bioartificial liver support systems (BALSS). In this work the viability and metabolic capacity of PPH and C3A cells cultured in different media were compared. Also, because the cells come into direct or indirect contact with human blood components in BALSS, the effects of human complement on survival and functions of the cells was evaluated. For short-term culture, maintenance of PPH viability was essential for retention of P450IA1 activity (r = 0.882, p < 0.01) and effective ammonia clearance (r = -0.791, p < 0.01). When cell viability was below 60% P450IA1 activity could not be recorded and nitrogen elimination activity significantly diminished. In contrast to PPH, ammonia levels were markedly increased for C3A cells in all culture media tested (p < 0.01). Ammonia increase correlated with C3A viability (r = 0.896, p < 0.05). PPH metabolic function was superior to that of the C3A cell line when evaluated by P450IA1 activity, ammonia removal, and amino acid metabolism. When PPH were incubated in human plasma (HP) or human serum (HS) there was rapid and irreversible deterioration of viability occurring within 9 h. This toxic effect could be prevented by the inactivation of complement. When sodium citrate dissolved in dextrose was added to medium, there was considerable damage to both PPH and the C3A cell line. However, there was no demonstrable toxic effect when hepatic cells of either type were exposed to heparin. We conclude that PPH cultivated in complement-inactivated HP or HS are to be preferred to C3A for clinical application of BALSS, and that heparin should be preferred for anticoagulation in BALSS.
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PMID:Comparison of porcine hepatocytes with human hepatoma (C3A) cells for use in a bioartificial liver support system. 978 66

Among other functions, the liver serves to regulate both glucose and nitrogen economy in the body, and in humans, the amino acid glutamine is a major gluconeogenic substrate and the primary extrahepatic ammonia shuttle. Accordingly, the liver acinus possesses a unique heterogeneous metabolic architecture suited to carry out these functions with glutamine-consuming urea cycle and gluconeogenic enzymes in the periportal hepatocytes and a high capacity for glutamine synthesis in the perivenous hepatocytes, resulting in net glutamine balance across the hepatic bed under most conditions. Cytoplasmic levels of glutamine are significantly governed by the activity of the System N transporter in the plasma membrane of parenchymal cells; in this capacity, this glutamine carrier has been shown to represent a rate-limiting step in metabolism via glutaminase. The unique properties of System N allow it to rapidly adapt in support of the dynamic demands of whole body ammonia and glucose homeostasis. In contrast to System N in normal hepatocytes, human hepatoma cells take up glutamine at rates several-fold faster through a broad-specificity higher affinity transporter with characteristics of System ASC or B0. It is currently hypothesized that the expression of this high activity carrier by hepatoma cells combined with accelerated metabolism and tumor-induced derangements in hepatocellular architecture result in net glutamine consumption, and may underlie the diminished plasma glutamine levels observed in patients with hepatocellular carcinoma (HCC). The transport of glutamine through System ASC has been shown to regulate growth in some human hepatoma cells, which suggests this transporter may warrant consideration as a therapeutic target for HCC.
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PMID:Glutamine transport and human hepatocellular transformation. 1048 91

Asparaginase (ASNase) is a widely used and successful agent against childhood acute lymphoblastic leukemia (ALL). Asparaginase cleaves asparagine (Asn) to give aspartic acid and ammonia, thereby depleting free Asn in the blood. However, treatment with ASNase has been implicated in significant reduction of plasma levels of the coagulation serine protease inhibitor (serpin) antithrombin III (AT3), predisposing patients to thromboembolic complications. Our investigation was designed to delineate the biochemical mechanism of AT3 depletion that can occur in the plasma of ALL patients undergoing ASNase therapy. SDS-PAGE showed no cleavage of purified AT3 following treatment with ASNase. Furthermore, purified AT3 treated with ASNase demonstrated no decrease in inhibitory activity. Human plasma and whole blood treated with approximate therapeutic concentrations of ASNase showed no loss of AT3 activity as detected by a plasma-based factor Xa inhibition assay. Treatment of a confluent monolayer of HepG2 (hepatocarcinoma) cells with ASNase showed no gross loss in AT3 message levels detected by rtPCR. However, a decrease of cell viability was observed in cultures treated with ASNase. Interestingly, medium from HepG2 cells treated with ASNase showed a marked decrease in secretion of AT3 and another serpin, heparin cofactor II. Collectively, these data show that ASNase has no direct effect on AT3 in blood or plasma, but that ASNase may affect plasma levels of AT3 by interfering with translation and/or secretion of the protein in liver cells.
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PMID:Insight into the mechanism of asparaginase-induced depletion of antithrombin III in treatment of childhood acute lymphoblastic leukemia. 1086 29

Chronic portosystemic encephalopathy (CPSE) is uncommon, and its management has yet to be determined. We have been able to control five cases of CPSE using transjugular retrograde obliteration (TJO), and we report our clinical results with this technique. All of the five patients were suffering from cirrhosis and had gastric varices and large gastrorenal shunts. According to Sherlock's classification, the grade of encephalopathy was II in two patients, III in two, and IV in one. According to Child's classification, one had class B and four had class C cirrhosis. TJO was performed using a 6-F angiographic catheter with an occlusive balloon 20 mm in diameter. Absolute ethanol and 5% ethanolamine oleate with iopamidol were used to obliterate the gastrorenal shunt. The gastrorenal shunt was successfully obliterated, and the encephalopathy improved to grade 0 after TJO in all cases. The portal flow volume increased significantly from 542 +/- 189 to 992 +/- 139 mL/min (p < 0.01). The plasma ammonia levels before and after TJO were 189 +/- 40 and 51 +/- 23 microg/dL, and the indocyanine green retention rates at 15 min were 44 +/- 13% and 27 +/- 12%, with both changes being significant (p < 0.01). Minor complications observed were fever of over 38 degrees C and tarry stools due to hemorrhagic gastritis in one patient, which was being controlled conservatively. One patient died of hepatocellular carcinoma 27 months after TJO. The other four patients survived without recurrence of CPSE 17-74 months (44 +/- 24 months) after TJO. We conclude that TJO can be adopted as a safe and effective treatment for CPSE.
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PMID:Transjugular retrograde obliteration for chronic portosystemic encephalopathy. 1102 85

The effect of segmental transcatheter arterial chemoembolization (TAE) on serum amino acid levels and liver function were studied in 23 patients with HCC associated with hepatitis virus C (22 patients) or alcoholism (1 patient), with compensated liver cirrhosis (Child A 18 patients, Child B 5 patients). Serum levels of branched-chain amino acids (BCAA), tyrosine, branched-chain amino acids to tyrosine ratio (BTR), ammonia, total bilirubin and albumin, and prothrombin times were measured before and after TAE (24 h, 7 and 14 days). The BTR was increased significantly 24 h after TAE (p<0.001) and gradually decreased to pre-TAE levels. Serum tyrosine levels decreased at 24 h after TAE (p<0.005) and later increased. Serum BCAA levels increased slightly at 7days after TAE and were decreased at 14 days after TAE. This results indicated that the increased BTR was due primarily to the decreased tyrosine level at 24 h after TAE. Serum ammonia levels gradually decreased after TAE and the prothrombin time and serum levels of total bilirubin and albumin were not significantly changed. In this study, segmental TAE had little influence on liver function, and the BTR unexpectedly increased at 24 h after TAE. These results suggest that segmental TAE has minimal side effects and may have a beneficial effect on amino acid metabolism.
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PMID:Effect of segmental transcatheter arterial chemoembolization on branched chain amino acids and tyrosine ratio in patients with hepatocellular carcinoma. 1102 1

Small conductance Ca2+-activated K+ (SK) channels have been cloned from mammalian brain, but little is known about the molecular characteristics of SK channels in nonexcitable tissues. Here, we report the isolation from rat liver of an isoform of SK3. The sequence of the rat liver isoform differs from rat brain SK3 in five amino acid residues in the NH3 terminus, where it more closely resembles human brain SK3. SK3 immunoreactivity was detectable in hepatocytes in rat liver and in HTC rat hepatoma cells. Human embryonic kidney (HEK-293) cells transfected with liver SK3 expressed 10 pS K+ channels that were Ca2+ dependent (EC(50) 630 nM) and were blocked by the SK channel inhibitor apamin (IC(50) 0.6 nM); whole cell SK3 currents inactivated at membrane potentials more positive than -40 mV. Notably, the Ca2+ dependence, apamin sensitivity, and voltage-dependent inactivation of SK3 are strikingly similar to the properties of hepatocellular and biliary epithelial SK channels evoked by metabolic stress. These observations raise the possibility that SK3 channels influence membrane K+ permeability in hepatobiliary cells during liver injury.
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PMID:Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3. 1124


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