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)

DNR can be targeted to the liver by linking to galactosylated human serum albumin (AG). The linkage is stable in the blood stream and allows the release of active DNR after endocytosis of the conjugate by the target cells. Receptors for AG are present at the cell membrane of hepatocytes, primary human hepatoma cells and lung metastases. After i.v. administration of AG-DNR more than 70% of the drug is taken up by the liver and in rats 50% of DNR is eliminated in the bile after 16 h. Nude mice bearing human hepatoblastoma cells implanted s.c. were treated twice a week with a dose equivalent to 6.6 mg/kg of DNR either for the free drug or the conjugate AG-DNR. After 7 injections, tumor growth is inhibited in both case, however, the conjugate seems more active and is at least twice less toxic in terms of LD50. A phase I clinical trial of AG-DNR on 11 patients bearing hepatocarcinoma revealed that despite a transitory hyperthermia (37-38 degrees C) during the first day of the 4 day-perfusion, and modifications of hepatic enzymes in 3 cirrhotic patients, no hematologic and cardiac toxicity could be detected. A subjective response has been obtained in half of the patients with a decrease of plasmatic alpha-foetoprotein levels by more than 50% in 4 patients and one complete remission of more than 23 months with disparition of pulmonary metastases.
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PMID:[Targeting of anthracyclines and hepatomas]. 303 67

A radioimmunoassay for 3 beta-hydroxy-5-cholenoyl glycine in human urine has been developed. The antiserum was elicited with the antigen in which the steroid hapten is linked to a bovine serum albumin through the C-19 position. The [125I]-tyrosine derivative of the hapten was used as radioligand. The standard curves were linear ranging from 10 to 320 ng/mL. The cross-reactivities with other bile acids were not detectable and below 0.3% with cholesterol. Sample preparation includes extraction of 3 beta-hydroxy-5-cholenoyl glycine from urine and solvolysis of the sulfates--main form present in urine. Urinary excretion of 3 beta-hydroxy-5-cholenoyl glycine was 0.373 +/- 0.133 mumol/day in healthy adults. Urinary excretion of 3 beta-hydroxy-5-cholenoyl glycine increased in chronic liver dysfunction, hepatoma and obstructive jaundice in this order.
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PMID:Radioimmunoassay of urinary 3 beta-hydroxy-5-cholenoyl glycine in hepatobiliary disease. 303 57

Between March 1982 and September 1983, 40 inpatients (25 men and 15 women, mean age 53 years) with alcoholic cirrhosis and total serum bilirubin greater than or equal to 5 mg per dl were studied. Those with hepatocellular carcinoma, renal failure, hyponatremia, septicemia, spontaneous bacterial peritonitis, gastrointestinal bleeding, and hepatic coma were excluded. Patients were studied for 28 days. The two groups were offered an oral diet containing 40 kcal per kg per day. Patients in the supplementary parenteral nutrition group received 40 kcal per kg per day and 200 mg nitrogen per kg per day using a central catheter. The major endpoint was total serum bilirubin on Day 28. On admission, serum bilirubin was not significantly different in the two groups: oral group, 12.5 +/- 6.6 mg per dl; supplementary parenteral nutrition group, 12.3 +/- 8.5 mg per dl. On Day 28, serum bilirubin was lower in the supplementary parenteral nutrition group (2.5 +/- 1.4 mg per dl) than in the oral group (4.1 +/- 2.2 mg per dl) (p less than 0.02). Serum bilirubin was also lower in the supplementary parenteral nutrition group than in the oral group on Days 7, 14 and 21 (p less than 0.05). Analysis of covariance, considering serum bilirubin on admission and at randomization and time between admission and randomization, confirmed these results. On Day 28, anthropometric parameters, serum transferrin, prealbumin and retinol-binding protein were higher in the supplementary parenteral nutrition group, but the differences were not significant. Serum albumin was significantly lower in the supplementary parenteral nutrition group. The incidence of encephalopathy and sepsis was not significantly different between the two groups.
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PMID:A randomized clinical trial of supplementary parenteral nutrition in jaundiced alcoholic cirrhotic patients. 308 33

The present study was designed to investigate whether plasma lipoproteins and albumin can affect the basal synthetic rate of apolipoproteins in differentiated rat hepatoma cells (Fao) incubated in serum-free medium. The synthesis of apolipoproteins was measured by the incorporation of [35S]methionine into medium lipoproteins isolated by density gradient ultracentrifugation. Under all the experimental conditions used, Fao cells synthesized almost exclusively apolipoprotein E. When cells were incubated in the presence of 5-10% rat plasma the synthesis of apolipoprotein E increased 2-3-fold; lipoprotein-deficient serum had a negligible effect. Fatty acid-poor bovine serum albumin (BSA), which had been found to reduce very-low-density lipoprotein secretion in isolated rat hepatocytes, did not modify the synthesis of apolipoprotein E. When Fao cells were incubated in medium containing rat plasma lipoprotein fractions, the synthesis of apolipoprotein E increased. The d less than 1.090 g/ml plasma lipoprotein fraction had the major stimulatory effect. Increased apolipoprotein E synthesis was observed when cells were incubated in the presence of lipids extracted from rat plasma lipoproteins. These results suggest that the intracellular accumulation of lipoprotein-lipids plays an important role in regulating apolipoprotein E synthesis in Fao cells.
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PMID:Modulation of the synthesis of apolipoproteins in rat hepatoma cells. 319 28

Sn-protoporphyrin IX (SnPP), an inhibitor of heme oxygenase and a potential therapeutic agent for neonatal hyperbilirubinemia, is bound tightly by hemopexin. The apparent dissociation constant (Kd) at pH 7.4 is 0.25 +/- 0.15 microM, but estimation of the Kd for the SnPP-hemopexin complex is hampered by the fact that at physiological pH SnPP exists as monomers and dimers, both of which are bound by hemopexin. SnPP is readily displaced from hemopexin by heme (Kd less than 1 pM). The hemopexin-SnPP interaction, like that of heme-hemopexin, is dependent on the histidine residues of hemopexin. However, as expected from the differences in the coordination chemistries of tin and iron, the stability of the histidyl-metalloporphyrin complex is lower for SnPP-hemopexin than for mesoheme-hemopexin. Nevertheless, when SnPP binds to hemopexin, certain of the ligand-induced changes in the conformation of hemopexin which increase the affinity of the protein for its receptor are produced. Binding of SnPP produces the conformational change in hemopexin which protects the hinge region of hemopexin from proteolysis, but SnPP does not produce the characteristic increase in the ellipticity of hemopexin at 231 nm that heme does. Competition experiments confirmed that human serum albumin (apparent Kd = 4 +/- 2 microM) has a significantly lower affinity for SnPP than does hemopexin. Appreciable amounts of SnPP (up to 35% in adults and 20% in neonates) would be bound by hemopexin in the circulation, and the remainder of SnPP would be associated with albumin due to the latter's high concentration in serum. Essentially no non-protein-bound SnPP is present. Importantly, SnPP-hemopexin binds to the hemopexin receptor on mouse hepatoma cells with an affinity comparable to that of heme-hemopexin and treatment of the hepatoma cells with SnPP-hemopexin causes a rapid increase in the steady state level of heme oxygenase messenger RNA. These results show that hemopexin participates in the transport of SnPP to heme oxygenase and in its regulation by SnPP.
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PMID:Interaction of hemopexin with Sn-protoporphyrin IX, an inhibitor of heme oxygenase. Role for hemopexin in hepatic uptake of Sn-protoporphyrin IX and induction of mRNA for heme oxygenase. 337 22

As tested by DNase I digestion, the chromatin structure in several regions 5' to the rat serum albumin gene varies in tissues and cell lines that differ in transcription rate of this gene. Three DNase I-hypersensitive regions were found in hepatocyte nuclei but not in kidney cell nuclei. The sites were approximately 2.8 kbp (site 1), 0.2 kbp (site 2), and 0.05 kbp (site 3) upstream from the cap site of the gene. In rat fetal liver tissue and rat hepatoma cell lines (FaO, C2, and C2-rev7), as well as in cultured primary hepatocytes where the rate of albumin gene transcription is lower than in adult liver, hypersensitive site (HSS) 1 was absent while sites 2 and 3 were present. In addition, the C2 cell line, which does not express albumin mRNA, contains a different HSS at position -1.5 kbp. Factors (proteins) bound to sites 2 and 3 may allow cell-specific transcription, but the additional factor interaction at site 1 could be required for a maximal rate of albumin gene transcription.
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PMID:DNase I-hypersensitive sites in the 5'-flanking region of the rat serum albumin gene: correlation between chromatin structure and transcriptional activity. 346 9

The specificity of protein labeling by an affinity label of glucocorticoid receptors, dexamethasone 21-mesylate (Dex-Mes), was investigated using bovine serum albumin (BSA) as a model. During the early stages of [3H]Dex-Mes labeling at pH 8.8, approximately 90% of the covalent bond formation occurred at the one non-oxidized cysteine (Cys-34) of BSA. The nonspecific labeling was equally distributed over the rest of the BSA molecule. [3H]Dex-Mes labeling of Cys-34 was totally, and specifically inhibited by nearly stoichiometric amounts of the thiol-specific reagent methyl methanethiolsulfonate (MMTS). Thus both Dex-Mes and MMTS appear to react very selectively with thiols under our conditions. In reactions with hepatoma tissue culture (HTC) cell glucocorticoid receptors, MMTS was equally efficient in preventing [3H]dexamethasone binding to receptors and [3H]Dex-Mes labeling of the 98-kDa receptor protein. These results indicate that Dex-Mes labeling of the glucocorticoid receptor involves covalent reaction with at least one cysteine in the steroid binding site of the receptor. Small (approximately 1600-dalton) fragments of the [3H]Dex-Mes-labeled 98-kDa receptor were generated by limit proteolysis with trypsin, chymotrypsin, and Staphylococcus aureus V8 protease under denaturing conditions. Data from these fragments on 15% sodium dodecyl sulfate-polyacrylamide gels were consistent with all of the covalent [3H] Dex-Mes being located on one or a few cysteines in one approximately 15-residue stretch of the receptor. Further studies revealed no differences in the limit protease digestion patterns of activated and unactivated [3H]Dex-Mes-labeled receptors with trypsin, chymotrypsin, or V8 protease under denaturing conditions. These data suggest that activation does not cause any major covalent modifications of the amino acids immediately surrounding the affinity-labeled cysteine(s) of the steroid binding site.
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PMID:Selective covalent labeling of cysteines in bovine serum albumin and in hepatoma tissue culture cell glucocorticoid receptors by dexamethasone 21-mesylate. 359 34

The bidirectional surface transfer of free cholesterol (FC) between Fu5AH rat hepatoma cells and human high density lipoprotein (HDL) was studied. Cells and HDL were prelabeled with [4-14C]FC and [7-3H]FC, respectively. Influx and efflux of FC were measured simultaneously from the appearance of 3H counts in cells and 14C counts in medium. Results were analyzed by a computerized procedure which fitted sets of kinetic data to a model assuming that cell and HDL FC populations each formed a single homogeneous pool and that together the pools formed a closed system. This analysis yielded values for the first-order rate constants of FC influx and efflux (ki and ke), from which influx and efflux of FC mass (Fi and Fe) could be calculated. With normal HDL, the uptake and release of FC tracers conformed well to the above-described model; Fi and Fe were approximately equal, suggesting an exchange of FC between cells and HDL. HDL was depleted of phospholipid (PL) by treatment with either phospholipase A2 or heparin-releasable rat hepatic lipase, followed by incubation with bovine serum albumin. PL depletion of HDL had little or no effect on ki, but reduced ke, indicating that PL-deficient HDL is a relatively poor acceptor of cell cholesterol. The reduction in ke resulted in initial Fi greater than Fe and, thus, in net uptake of FC by the cells. This result explained previous results demonstrating net uptake of FC from PL-depleted HDL. In the presence of an inhibitor of acyl coenzyme A:cholesterol acyltransferase, the steady state distribution of FC mass between cells and HDL was accurately predicted by the ratio of rate constants for FC flux. This result provided additional validation for describing FC flux in terms of first-order rate constants and homogeneous cell and HDL FC pools.
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PMID:The bidirectional flux of cholesterol between cells and lipoproteins. Effects of phospholipid depletion of high density lipoprotein. 370 Mar 71

A 23-kilobase-pair segment of DNA containing the entire mouse serum albumin gene as well as 2.2 kilobase pairs of 5' and 4.3 kilobase pairs of 3' flanking sequences has been introduced into pSV2dhfr, a plasmid in which expression of the mouse dihydrofolate reductase cDNA is under the control of simian virus 40 sequences. This vector, pSV2dhfr-alb, was used to transfect differentiated and variant dedifferentiated rat hepatoma cells. Nine independent clones of transfected differentiated cells secrete considerable amounts of mouse albumin, while the expression of the normal rat albumin is the same as in nontransfected cells. In contrast, only small amounts of mouse and rat albumin are produced by transfected dedifferentiated cells. The amounts of albumin mRNA present in the cells are consistent with the amounts of albumin produced. These results show that a transfected gene can be regulated in a fashion consistent with the overall differentiation profile of the cell.
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PMID:Expression of the mouse serum albumin gene introduced into differentiated and dedifferentiated rat hepatoma cells. 385 30

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


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