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 purified beef heart cAMP-dependent protein kinase catalytic subunit on tyrosine aminotransferase activity in intact cultured rat H35 hepatoma cells was directly tested by micro-injection using human red blood cell ghosts as vehicles. Although the micro-injection procedure itself produced temporary fluctuations in protein synthesis and in tyrosine aminotransferase activity in H35 cells, after a recovery period of 8-12 h, these parameters returned to normal in parallel with restoration of full inducibility of the aminotransferase by both 8-Br-cAMP and dexamethasone. Eight to sixteen hours after fusion of H35 cells with unloaded ghosts, ghosts loaded with bovine serum albumin or mock-loaded with the partially purified protein kinase catalytic subunit, no significant change in the activity of the aminotransferase was detected. In contrast, fusion with ghosts loaded with the catalytic subunit at concentrations between 0.1-2 mg/ml caused reproducible 2-3-fold increases in enzyme activity. Homogeneous preparations of the catalytic subunit exhibited even greater potency as an inducer. The effect was both time- and concentration-dependent and was abolished by inactivation of the catalytic subunit with N-ethylmaleimide prior to loading. The partially purified inhibitor of protein kinase from beef heart, while not affecting basal tyrosine aminotransferase activity, selectively inhibited the ability of 8-Br-cAMP but not that of dexamethasone to stimulate the activity of this enzyme. In addition, micro-injection of the pure regulatory subunit of the kinase blocked the response of the aminotransferase to low concentrations of 8-Br-cAMP. These results provide strong support for the proposition that the catalytic subunit of protein kinase mediates the effects of cAMP on the synthesis of tyrosine aminotransferase.
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PMID:Direct evidence that the protein kinase catalytic subunit mediates the effects of cAMP on tyrosine aminotransferase synthesis. 613

The stability of the expression of six differentiated functions was examined during long-term cultivation of rat hepatoma cells. Faza 967 cell line--a clonal descendant of the Reuber H35 hepatoma--is characterized by the activity of tyrosine aminotransferase (TAT) and gluconeogenetic enzymes; secretion of serum albumin; and the presence of liver isozymes of alcohol dehydrogenase (ADH-L), aldolase (aldolase-B) and five isozymes of lactate dehydrogenase (LDH). During the 3-year-long cultivation of Faza 967 cells TAT specific activity, inducibility, and albumin production were reduced drastically whereas the expression of the three liver-specific isozymes examined was maintained. The majority of Faza 967 cells were able to perform gluconeogenesis after 3 years of continuous cultivation. Our results show that long-term cultivation of hepatoma cells may change the expression of certain liver-specific functions independently of the expression of other differentiated functions.
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PMID:Changes in the expression of differentiated functions during long-term cultivation of rat hepatoma cells. 613 53

The expression of liver-specific functions of different dexamethasone-resistant variants derived from a well-differentiated dexamethasone-sensitive Reuber H35 rat hepatoma cell line (Faza 967) was examined during long-term cultivation. The dexamethasone-sensitive Faza 967 cells are characterized by the activity of tyrosine aminotransferase (TAT) and gluconeogenic enzymes, secretion of serum albumin, and the presence of liver isozymes of alcohol dehydrogenase (L-ADH), aldolase (aldolase-B), and five isoenzymes of lactate dehydrogenase (LDH). The hormone-resistant cells undergo a very dramatic change in expression of most liver-specific functions (dedifferentiation) during long-term culture, in contrast to the sensitive cells in which only certain functions (TAT activity, inducibility, and synthesis of serum albumin) exhibit considerable changes. The hormone-dependent growth sensitivity and the expression of other differentiated functions is not controlled in coordinated way in Faza 967 cells. The time course of the expression of liver-specific functions shows that the cells are resistant before they became 'dedifferentiated', i.e., loss of these liver-specific functions is not a prerequisite of the establishment of the hormone-resistant state.
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PMID:Expression of differentiated functions in dexamethasone-resistant hepatoma cells. 614 Nov 18

The inhibitory effect of human alpha-fetoprotein on the protein synthesis (incorporation of [3H]leucine into the total protein fraction) weas observed in a rabbit reticulocyte lysate cell-free system. The incorporation was inhibited to 50% of the control level by 14-16 microM alpha-fetoprotein, and decreased to about 15% at a concentration higher than 40 microM. An almost identical dose dependence was obtained between fetal alpha-fetoprotein and hepatoma-derived alpha-fetoprotein. This inhibitory effect on the protein synthesis was due to the interference of alpha-fetoprotein to the 40 S initiation complex formation from the ternary complex (eukaryotic initiation factor 2.GTP.Met-tRNAfMet). In contrast human serum albumin purified from fetal cord sera did not exhibit this inhibition under the same conditions. These results indicate that alpha-fetoprotein may function as a regulator of the protein synthesis in the fetal stage.
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PMID:Inhibitory effect of alpha-fetoprotein on protein synthesis in a reticulocyte lysate cell-free system. 617 33

Human alpha 1-microglobulin (alpha 1-m) levels were studied in the sera and urine of patients with various liver diseases. In patients with acute hepatitis and chronic hepatitis it was almost within the normal range. A significant decrease of serum alpha 1-m, however, was demonstrated in patients with compensated liver cirrhosis (p less than 0.05) as well as in those with decompensated liver cirrhosis (p less than 0.001). The most striking decrease was noted in patients with fulminant hepatitis (p less than 0.001). Its concentration in hepatoma was generally within the normal range, but there was 1 hepatoma case with the high concentration of alpha 1-m. Serum alpha 1-m levels correlated significantly with serum albumin, plasma fibrinogen and cholinesterase activity. As compared with the level in normal individuals, the patients with decompensated liver cirrhosis had significantly low urinary alpha 1-m (p less than 0.005), reflecting the findings for sera. These results indicated that the liver plays an important role in alpha 1-m synthesis, and its quantitation may be used for evaluating severe liver damage.
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PMID:Human alpha 1-microglobulin in various hepatic disorders. 619 36

Fasting serum levels of total and free tryptophan, and free fatty acids and albumin, were measured and compared by blood biochemical analysis in patients with hepatobiliary disease and neuropsychiatric symptoms. The serum total tryptophan level tended to be elevated in patients with chronic active hepatitis, hepatic coma and obstructive jaundice, but not significantly. The serum free tryptophan level was significantly elevated in patients with chronic active hepatitis, liver cirrhosis, primary hepatocellular carcinoma and obstructive jaundice. The free tryptophan level was related to the decreased serum albumin level and elevated serum free fatty acid levels, which seems to indicate a connection with liver parenchymal function. The level, however, seemed not to correlate with neuropsychiatric symptoms.
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PMID:Clinical evaluation of serum levels of tryptophan in hepatobiliary disease. 624 22

Mitochondria were isolated from whole homogenates of normal liver and Novikoff hepatomas using reorienting rate zonal centrifugation on sucrose gradients. The activities of several mitochondrial-specific enzymes and ultrastructure were compared in the two tissues. Our results indicate that cytochrome oxidase, lipoamide dehydrogenase, malate dehydrogenase, and succinate dehydrogenase activities are all higher in liver homogenates than in Novikoff hepatoma homogenates. Mitochondrial hexokinase, however, is much greater in the hepatoma than in liver. The activity of these enzymes in isolated mitochondria displayed a much different pattern. Both cytochrome oxidase and succinate dehydrogenase activities were higher in hepatoma mitochondria than in liver mitochondria. Lipoamide dehydrogenase and malate dehydrogenase, conversely, were higher in liver mitochondria. Hexokinase was found to be virtually absent in liver mitochondria but plentiful in hepatoma mitochondria. Ultrastructural studies have shown that the hepatoma mitochondria are much smaller in size, which results in a decreased rate of migration into the gradient. These studies have also shown that normal liver consists of predominantly "condensed" forms of mitochondria, whereas hepatoma contained a majority of "twisted" species. Experiments using 1% bovine serum albumin in the homogenization procedures and in the gradient have confirmed earlier observations that bovine serum albumin is essential for optimal isolation of neoplastic mitochondria.
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PMID:Characteristics of mitochondria isolated by rate zonal centrifugation from normal liver and Novikoff hepatomas. 624 94

A retrospective study of 211 patients with proven hepatocellular carcinoma (HCC) was made. The commonest symptoms were anorexia and malaise (73%). Five patients (2.5%) had near-normal biochemical tests despite the presence of massive tumors. Diagnostic yield from angiography, percutaneous peritoneoscopic biopsy, or scintiscanning was 87-98%. Three percent of the patients had resectable tumors. Median survival for patients with untreated disease was 3.5 weeks. Apart from histology, the total serum bilirubin level was the only factor of prognostic value. Only 12 patients had preexisting symptomatic cirrhosis. When compared with 80 patients with symptomatic postnecrotic cirrhosis without malignancy, patients with HCC had higher SGOT:SGPT ratio, Higher serum albumin levels, and higher platelet counts. There was only minimal overlap of patients with symptomatic postnecrotic cirrhosis and those with HCC. The authors conclude that their patients with HCC appeared late for treatment. A probable difference in the development of symptomatic postnecrotic cirrhosis and of HCC with asymptomatic postnecrotic cirrhosis is suggested.
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PMID:Clinical features of hepatocellular carcinoma: review of 211 patients in Hong Kong. 626 41

Recent evidence suggests that hepatitis B virions (HBV) and HBsAg particles contain receptors for polymerized human serum albumin (pHSA). We studied, by immunohistochemical techniques, the relationship between HBsAg and pHSA receptors in liver tissue from eight patients with chronic HBV infection and in a human hepatocellular carcinoma cell line (PLC/PRF/5) producing HBsAg. Both parallel sections and double fluorescent antibody staining of liver tissue demonstrated that only HBsAg-containing hepatocytes expressed pHSA receptors. The receptors could not be demonstrated in eight HBsAg negative livers. Sequential studies of PLC/PRF/5 cells revealed that pHSA and HBsAg emerged simultaneously in the cytoplasm, on the cell surface, and in the supernatant culture media. These findings indicate that pHSA receptors are closely associated with HBsAg during its synthesis and secretion by hepatocytes and suggest that the receptors are HBV-specific.
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PMID:Presence of receptors for polymerized albumin in HBsAg-containing hepatocytes and hepatoma cell line. 626 78

Prognosis of 600 consecutive patients with hepatocellular carcinoma was analyzed in relation to treatment. They were divided into three stages based on four parameters of advanced disease: ascites, tumor greater than 50% of the two-dimensional size of the liver, serum albumin below 3 gm per dl, and serum bilirubin above 3 mg per dl. Stage I had none of these signs; Stage II one or two signs, and Stage III three or all signs. Of 600 patients, 98 had resection, 333 had nonsurgical treatment (158 treated by intraarterial chemotherapy, 94 systemic chemotherapy, 77 transcatheter embolization, and 4 others) and 169 no treatment. The median survival of untreated patients was only 1.6 months from diagnosis, and no untreated Stage III patient lived more than 3 months; there was a median survival of 0.7 month. Surgically treated patients lived significantly longer than nonsurgical patients of comparable stages; median survival was 19.6 months in the former and 2.8 months in the latter. Whereas Stage I patients did fairly well without treatment, chemotherapy significantly prolonged survival of patients of Stages II and III. These results suggest that early diagnosis and hepatic resection improve prognosis in patients with hepatocellular carcinoma in the areas where this cancer frequently emerges unicentrically. In view of the generally poor prognosis, liver transplantation is recommended when resection is not possible or indicated, and before extrahepatic metastasis occurs.
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PMID:Prognosis of primary hepatocellular carcinoma. 631 64


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