Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six-year survival of cirrhosis was assessed in a series of 1155 consecutive patients (751 men, 404 women). Among the men, 33% were alcoholics and 18% were HBsAg positive; corresponding figures for the women were 15% and 6% respectively. Features of decompensation at first presentation were observed in 63% of the patients. Six-year survival was 54% in compensated and 21% in decompensated patients. No significant differences in survival were found between alcoholics and nonalcoholics. Leading causes of death were liver failure (49%), hepatocellular carcinoma (22%), and bleeding (13%). The prognostic role of 21 variables was evaluated separately in compensated and decompensated patients by the Cox's regression model. The following variables were found to be significant predictors of death risk in compensated patients: male sex, HBsAg positivity, age, prothrombin time prolongation, and esophageal varices. In decompensated disease the significant indicators of death risk were: hepatocellular carcinoma, encephalopathy, hemorrhage, SGOT, esophageal varices, gamma globulins, prothrombin time prolongation, continued abuse of alcohol, HBsAg positivity, gamma glutamyl transpeptidase, and cholinesterase. A simple prognostic index based upon the relative risk coefficient of the significant variables is suggested.
 ...
PMID:Survival and prognostic indicators in compensated and decompensated cirrhosis. 300 9

Human prothrombin cDNA has been expressed in mammalian cells to yield biologically active, fully gamma-carboxylated prothrombin. A 2.0-kilobase cDNA encoding full-length prothrombin was isolated from a human fetal liver library using a cDNA fragment recovered from a lambda gt11 human hepatoma expression library. Prothrombin cDNA was cloned into a mammalian expression vector and transfected into Chinese hamster ovary cells. Selection for expression of dihydrofolate reductase yielded cell lines secreting up to 0.55 microgram/ml of prothrombin. Recombinant prothrombin synthesized in the presence of vitamin K was quantitatively recovered from tissue culture medium by affinity chromatography using conformation-specific antibodies directed against the metal-stabilized, gamma-carboxylated conformer. The purified material migrated as a single band on denaturing polyacrylamide gels with an electrophoretic mobility equivalent to that of plasma-derived human prothrombin. Automated Edman degradation of recombinant prothrombin revealed a single amino-terminal sequence identical to that of plasma-derived prothrombin. Recombinant and plasma-derived prothrombin interacted similarly with antibodies specific for total prothrombin, abnormal des-gamma-carboxyprothrombin, and two metal-stabilized conformers of prothrombin. Recombinant prothrombin exhibited a specific coagulant activity equivalent to that of plasma-derived prothrombin. The gamma-carboxyglutamic acid analysis of recombinant prothrombin demonstrated 9.9 +/- 0.4 mol of gamma-carboxyglutamic acid/mol of prothrombin. These results represent the first description of the expression of a recombinant vitamin K-dependent protein in which all of the expressed protein is gamma-carboxylated.
 ...
PMID:Expression of completely gamma-carboxylated recombinant human prothrombin. 303 75

We measured plasma abnormal prothrombin (des-gamma-carboxy prothrombin; DCP) levels in normal subjects and in patients with hepatocellular carcinoma and other various diseases using the enzyme-linked immunosorbent assay developed by Motohara et al. (Pediatr Res 1985; 19: 354-357). Fifty-eight percent of 52 patients with hepatocellular carcinoma had elevated DCP levels; 24 of 28 patients with advanced or moderately advanced hepatocellular carcinoma were positive. By contrast, 50 normal controls, 13 pregnant women and 10 patients with acute hepatitis had normal levels. Three of 55 patients with chronic liver disease, and 6 of 32 patients with other malignancies, showed a slight increase. Thus, increased plasma DCP appears useful for the diagnosis of hepatocellular carcinoma. To elucidate the mechanism for the increase of DCP in hepatocellular carcinoma, we cultured a human hepatoma cell line, huH-2, and measured the levels of this abnormal prothrombin in the medium. The huH-2 cells produced large amounts of DCP in the medium without added vitamin K. It increased in a cell concentration- and time-dependent fashion. These cells produced no detectable amount of DCP in the medium with added vitamin K. Thus, human hepatoma cell line huH-2 produces DCP, and its production is dependent on the amount of vitamin K available in the medium. Des-gamma-carboxy prothrombin may be a useful tumor marker for the diagnosis of hepatocellular carcinoma.
 ...
PMID:Production of abnormal prothrombin (des-gamma-carboxy prothrombin) by hepatocellular carcinoma. A clinical and experimental study. 303 40

Prothrombin synthesis and secretion were studied in a human hepatoma cell line (Hep G2) incubated with 35S-methionine for 2 to 24 hours at 37 degrees C. Extracellular and intracellular prothrombin were detected by immunoprecipitation with affinity-purified antiprothrombin antibody. Incorporation of 35S-methionine into prothrombin was monitored by counting specific bands excised from 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Prothrombin represented 0.3% to 0.7% of total newly synthesized protein secreted into the media. Warfarin had no effect on total prothrombin synthesis (extracellular plus intracellular). However, warfarin inhibited secretion of newly synthesized prothrombin by 58% to 73% over a 2 to 4 hour period. This was accompanied by the intracellular accumulation of an immunoprecipitable species of prothrombin of 78 kd, 6 kd less than extracellular prothrombin. At the end of the 4-hour incubation with warfarin, intracellular prothrombin increased from 44% to 82% (twofold) of total prothrombin, whereas extracellular prothrombin decreased from 56% to 19% (threefold) of total prothrombin. After 24-hour incubation with warfarin, intracellular and extracellular immunoprecipitable prothrombin approached control values. Deglycosylation of extracellular and intracellular prothrombin with hydrofluoric acid (HF) resulted in a decrease in mol wt for both species to 66 kd. Endoglycosidase-H treatment, which digests "early mannosyl" residues, resulted in a decrease in the mol wt of the intracellular species of 8 kd with no effect on the extracellular species. Thus, the lower mol wt intracellular species that accumulates following early warfarin treatment is due to the presence of incompletely processed carbohydrate chain. The data are compatible with the hypothesis that optimum glycosylation and secretion require Vitamin K-dependent carboxylation.
 ...
PMID:Effect of warfarin on prothrombin synthesis and secretion in human Hep G2 cells. 304 Jan 56

In order to clarify an alteration in thyroid functions in patients with chronic liver diseases, serum total and free thyroxine (T4, FT4), total and free triiodothyronine (T3, FT3), total reverse T3 (rT3), thyrotropin (TSH), thyroxine-binding globulin (TBG) concentrations, and T3 uptake (T3U) were measured by radioimmunoassays in 53 patients with chronic hepatitis (CH), 24 patients with compensated liver cirrhosis (LC), 17 patients with hepatocellular carcinoma associated with LC (HCC), and 40 normal subjects. Serum T4, T3, and rT3 in CH, and serum rT3 in HCC were significantly increased, while serum T4 in LC and serum T3 in HCC were significantly decreased. Serum TBG was increased and T3U was decreased in these patients. Serum TBG in CH and LC correlated positively with transaminase, and inversely with prothrombin time. FT4 and T4/TBG ratios in CH and LC and FT3 and T3/TBG ratios in LC and HCC were significantly decreased. Although T4/TBG ratios in HCC and T3/TBG ratios in CH were significantly decreased, FT4 in HCC and FT3 in CH were not decreased. The ratio of rT3/T3 in CH and LC correlated with various liver function tests. FT3 in LC and HCC correlated inversely with BSP (45') and positively with KICG. No differences in serum TSH values were found between chronic liver diseases and normal subjects. From these results, it was concluded that the thyroid functions in patients with chronic liver diseases were affected by the decrease in serum thyroxine, elevated serum TBG, the degree of which is in proportion to that of the liver cell damage, and impaired peripheral conversion of T4 to T3, the degree of which is in proportion to that of the hepatic dysfunction.
 ...
PMID:Thyroid functions in patients with various chronic liver diseases. 314 45

Plasma levels of pipecolic acid, which is a minor metabolite of lysine, were determined by high-performance liquid chromatography in 22 patients with chronic liver disease, composed of 6 patients with chronic active hepatitis, 11 with liver cirrhosis and 5 with hepatocellular carcinoma. The plasma levels of pipecolic acid, when compared to those in normal subjects (1.00 +/- 0.08 nmoles per ml), were found to be significantly elevated (p less than 0.01) in patients with liver cirrhosis (1.93 +/- 0.24 nmoles per ml) and hepatocellular carcinoma (2.22 +/- 0.49 nmoles per ml), but did not show any significant change in patients with chronic active hepatitis. Plasma levels of pipecolic acid correlated positively with serum bile acid and bilirubin, and negatively with indocyanine green disappearance rate, cholinesterase and prothrombin time but not with plasma lysine levels. These results suggest that plasma levels of pipecolic acid increase almost parallel to the severity of liver damage, and that this increase in pipecolic acid may reflect the injury of liver peroxisomes which appear to be related to the degradation of pipecolic acid.
 ...
PMID:Plasma levels of pipecolic acid in patients with chronic liver disease. 335 9

Lung metastasis is a frequent cancer complication resulting in significant mortality. This study evaluates the effect of coumadin and cytoxan alone and in combination on lung metastases in rats challenged with Morris hepatoma 3924A. Seventy-seven male American Cancer Institute (ACI) rats weighing 200 g were studied. Thirty-seven rats received coumadin orally for six days, which resulted in a prothrombin time 2 times that of controls (30 sec). All rats received 1 X 10(5) clumped Morris hepatoma cells via tail vein injection. Animals were divided into four groups: Group I (controls, n = 20) received no antitumor treatment; group II rats (n = 20) received 25 mg/kg cytoxan intraperitoneally at the time of tumor challenge; group III animals (n = 19) received coumadin alone; while group IV (n = 18) received both coumadin and cytoxan. Rats were evaluated for number of lung metastases and lung weight at 3 weeks postinjection. Data was subjected to statistical analysis by the Student's test. The mean number of lung metastases were 580 +/- 45 in group I, 350 +/- 310 in group II, 330 +/- 263 in group III, and 200 +/- 161 in group IV (P less than .005 [IV] v [I], P less than .05 [IV] v [II], [III]), (P less than .05 [II] v [I]), (P less than .05 [III] v [I]). Mean lung weights were 2.597 g +/- 1.65 in group I, 2.049 g +/- 0.75 in group II, 1.898 g +/- 0.80 in group III, and 1,677 g +/- 0.31 in group IV. (P less than .025 [IV] v [I], P less than .05 [IV] v [II]).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Synergistic effect of coumadin and cytoxan in reducing lung metastases. 379 75

Hypercalcemia has not previously been recognized as a complication of advanced chronic liver disease without hepatoma. During a five-year period, 16 patients evaluated in the liver transplantation program at the University of Pittsburgh developed hypercalcemia. All had advanced chronic liver disease with mean total bilirubin concentration of 29.5 +/- 4.6 mg/dL (50.1 +/- 78.2 mumol/L) (mean +/- SEM) and prothrombin time 16.8 +/- 0.8s. The highest serum calcium level was 17.2 mg/dL (4.3 mmol/L). The mean serum calcium level was 11.7 +/- 0.3 mg/dL (2.93 +/- 0.075 mmol/L) with an ionized calcium level of 5.41 +/- 0.35 mg/dL (1.35 +/- 0.088 mmol/L) and a phosphorus level of 4.2 +/- 0.4 mg/dL (1.4 +/- 0.1 nmol/L). Mild to moderate renal insufficiency was present in 14 (87%) patients; the mean serum creatinine level was 2.8 +/- 0.4 mg/dL (247 +/- 35 mumol/L). In five (38%) patients parathyroid hormone was completely suppressed and in an additional five (38%) patients, it was in a range most compatible with nonhyperparathyroid hypercalcemia. The 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels were normal or low in the 11 patients in whom determinations were made. Hypercalcemia that is not due to hyperparathyroidism or hypervitaminosis D is a potential complication of advanced chronic liver disease.
 ...
PMID:Hypercalcemia. A complication of advanced chronic liver disease. 381 45

Vitamin K is required for the posttranslational formation of gamma-carboxyglutamyl residues in a number of plasma clotting factors. Interference with vitamin K action results in the appearance of abnormal (des-gamma-carboxy) forms of prothrombin in human plasma. Vitamin K-sufficient patients with primary hepatocellular carcinoma also secrete significant quantities of abnormal prothrombin; this response has now been studied in a rat model. Normal Buffalo strain rats had 9 micrograms/mL of circulating plasma abnormal prothrombin, whereas Buffalo strain rats carrying the transplantable Morris hepatoma tumor no. 7777 had 33 micrograms/mL at 3 weeks after transplant. Vitamin K-dependent carboxylase activity was normal in the liver of these rats, but very low in the tumor tissue. Rats carrying Morris hepatoma tumors no. 9618A and 5123D did not secrete significant amounts of abnormal prothrombin. Carboxylase activity in these tumors was 15 times that of the 7777 tumor. The data suggest that the secretion of abnormal prothrombin by hepatocellular tumors is the result of normal expression of the prothrombin gene by those tumors and a failure of the tumor to express the carboxylase gene.
 ...
PMID:Abnormal prothrombin in the plasma of rats carrying hepatic tumors. 381 18

We detected des-gamma-carboxy prothrombin, an abnormal prothrombin, in the serum of 69 of 76 patients (91 per cent) with biopsy-confirmed hepatocellular carcinoma (the mean level of the abnormal prothrombin was 900 ng per milliliter). In contrast, levels of the abnormal prothrombin were low in patients with chronic active hepatitis (mean, 10 ng per milliliter) or metastatic carcinoma involving the liver (mean, 42 ng per milliliter), and undetectable in normal subjects. In five patients treated with vitamin K there was no reduction in abnormal prothrombin, indicating that its presence was not due to vitamin K deficiency. Surgical resection of tumors in two patients and chemotherapy in one patient markedly reduced abnormal-prothrombin concentrations, which later increased with recurrence of disease. Serum alpha-fetoprotein levels correlated poorly with abnormal-prothrombin levels. Together, the assay for abnormal prothrombin and the alpha-fetoprotein assay identified 64 of 76 patients with hepatoma (84 per cent). Abnormal prothrombin may be useful in the laboratory diagnosis of primary hepatocellular carcinoma.
 ...
PMID:Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. 620 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>