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)

Reuber rat hepatoma cells (R-Y121B) cultured at 0.5% serum accumulated apoalkaline phosphatase in intact cells. When R-Y121B cells were cultured in the presence of bovine serum albumin, alkaline phosphatase activity increased in the cells, and the associated increase in enzyme activity differed amongst bovine serum albumin preparations. The treatment of bovine serum albumin with activated charcoal not only enhanced the effect of serum albumin on alkaline phosphatase activity, but also cancelled the differences due to different preparations of serum albumin. In contrast, no effect from serum albumin was observed in the increase of alkaline phosphatase activity in R-Y121B cell homogenates incubated at 37 degrees C. The activated-charcoal treatment of bovine serum albumin increased the amount of Zn2+ bound to the protein. When R-Y121B cells were cultured with bovine serum albumin, the concentration of Zn2+ in the cytosol fraction slightly increased. However, the effect of serum albumin on Zn2+ concentration in the cytosol fractions was independent of charcoal treatment. It was concluded that serum albumin with Zn2+ induces the activation of apoalkaline phosphatase due to Zn2+ binding.
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PMID:Activation of apoalkaline phosphatase by serum albumin with Zn2+ in rat hepatoma cells. 147 56

Hepatocellular carcinoma patients were categorized into three grades according to the extent of portal vein invasion by the tumor. Correlations between the extent of portal vein invasion and values of alpha-fetoprotein (AFP), and various biochemical tests were examined. The extent of portal vein invasion by the tumor significantly correlated with the values of glutamic oxaloacetic transaminase (GOT), glutamic oxaloacetic transaminase: glutamic pyrubic transaminase (GOT:GPT), lactic dehydrogenase (LDH), alkaline phosphatase, leucinaminopeptidase (LAP), gamma-glutamic transpeptidase (gamma-GTP) and log10AFP. Results of the multivariate logistic regression analysis showed the values of LAP, LDH, log10AFP and GOT:GPT to be statistically significant independent indicators of portal vein invasion by hepatocellular carcinoma. The calculated probability for portal vein tumor thrombus, which was derived from the results of a step wise multivariate logistic regression procedure, revealed high accuracy and specificity for predictability. To design effective therapy and to predict the prognosis, it would be beneficial to obtain additional information from this calculated probability in patients with hepatocellular carcinoma.
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PMID:Prediction of portal vein invasion by hepatocellular carcinoma: a correlations between portal vein tumor thrombus and biochemical tests. 164 38

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing doxorubicin (DOX) and galactosamine can be targeted to the hepatocyte galactose receptor for organ-specific chemotherapy of primary and metastatic liver cancer. Here we report the dose-dependent pharmacokinetics of this macromolecular conjugate. Following intravenous administration to mice most efficient liver targeting was seen at low dose (0.05 mg DOX kg-1), with receptor saturation observed using higher bolus doses. Repeated low dose bolus injections did not cause down-regulation of the galactose receptor and targeted drug delivery rates of greater than or equal to 2 micrograms DOX g-1 liver h-1 were achieved. DOX is released from such conjugates intracellularly via action of lysosomal proteinases. It was shown that isolated rat liver lysosomal enzymes (Tritosomes) can release unmodified DOX from the peptidyl side chain Gly-Phe-Leu-Gly at a rate greater than or equal to 3 micrograms DOX g-1 liver h-1 i.e. the hydrolytic capacity is greater than the observed rate of drug delivery to the liver lysosomes in vivo. Although most conjugate would be captured by normal hepatocytes following intravenous administration, it was shown that the human hepatoma cell line HepG2 retains the galactose receptor, accumulating and processing the conjugate efficiently. Potential dose limiting toxicities of such drug conjugates could include cardio- or hepatotoxicity. Administration of conjugate reduced the 15 min heart level of DOX approximately 100-fold compared with that observed for an equivalent dose of free drug. Preliminary experiments showed that plasma levels of alkaline phosphatase, alanine transaminase and asparate transaminase did not change following administration of HPMA copolymer-daunorubicin (DNR) (10 mg DNR kg-1) indicating no significant heptatoxicity.
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PMID:N-(2-hydroxypropyl)methacrylamide copolymers targeted to the hepatocyte galactose-receptor: pharmacokinetics in DBA2 mice. 164 46

It has been reported that hepatoma (HCC) cells produce abnormal proteins such as erytropietin, fibrinogen, prothrombin, and, recently, antithrombin III (AT III). In a preliminary report, we reported increased AT III levels in patients bearing HCC independent of their clinical liver status. The present study was performed to assess antithrombin III levels and other serological data present in patients with cirrhosis and in patients with cirrhosis and clinical findings of neoplastic disease. In 70 well-matched patients (47 with cirrhosis and 23 with cirrhosis and proven HCC) serum total cholesterol, albumin, prothrombin, alkaline phosphatase, AFP, aminotransferases, and AT III were determined. Together with AFP and alkaline phosphatase, patients with HCC had higher values of AT III (88 +/- 7%) and total cholesterol (184 +/- 17 mg/100 ml), as compared with cirrhotic patients (AT III 56 +/- 3.6%; total cholesterol 113 +/- 5 mg/100 ml) (P less than 0.001). No difference was observed between these two groups for albumin, prothrombin, and aminotransferases. In HCC patients, AT III levels were related to the total cholesterol level (R2 = 0.317), whereas in the cirrhotic patients it correlated with the prothrombin level (R2 = 0.274). These data suggest that in HCC patients a greater rate of synthesis of AT III occurs, whereas in cirrhotic patients lower levels of AT III occur due to impaired synthesis or increased catabolism of the protein. The serial determination of AT III in cirrhotic patients as a means of detecting neoplastic transformation is suggested.
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PMID:Hepatocarcinoma in cirrhosis. Is antithrombin III a neoplastic marker? 164 42

Three cases of bile duct necrosis owing to hepatic arterial infusion chemotherapy (HAI) were reported. Regarding HAI, transcatheter hepatic arterial embolization (TAE) was applied in two cases (hepatocellular carcinoma: 1; metastasis: 1) and 5-fluorouracil (continuous) combined with leucovorin (one shot) therapy (LV + 5-FU) was given to one metastatic case. In the data of blood biochemistry, serum alkaline phosphatase, gamma-glutamyl transpeptidase, and leucine aminopeptidase values characteristically elevated without the elevation of total bilirubin value. Hepatic tumors degenerated with necrosis in all cases and no viable cells were histologically recognized. Although the destruction of bile ducts was locally detected adjacent to these tumors in TAE cases and was more widespread in the LV + 5-FU case, these lesions were very similar in each case. Therefore, we concluded that both ischemia and drug toxicity induced bile duct necrosis and the necrosis around the bile duct was the secondary change due to the leaked bile juice.
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PMID:[Bile duct necrosis and hepatic necrosis following hepatic arterial infusion chemotherapy]. 165 26

Serum Mn-superoxide dismutase (Mn-SOD) was determined in patients with various liver diseases including 31 patients with primary biliary cirrhosis (PBC), 46 with hepatocellular carcinoma (HCC), 17 with liver cirrhosis (LC), 23 with chronic hepatitis (CH) and 12 patients with obstructive jaundice with an enzyme-linked immunosorbent assay using a specific monoclonal antibody. The serum level in patients with PBC (407 +/- 35 ng/ml, mean +/- SEM; n = 31) was significantly increased (p less than 0.01) compared with those of other liver diseases. Mn-SOD level did not correlate with total bilirubin level, gamma-glutamyl transpeptidase activity, alkaline phosphatase activity, alanine aminotransferase activity, IgM, or with ceruloplasmin level in the sera of the patients. When the patients with PBC were histologically subdivided into four groups according to Scheuer's classification (Scheuer PJ. Primary biliary cirrhosis. In: Scheuer PJ, ed. Liver biopsy interpretation. 3rd ed. London: Bailliere Tindall, 1980:47-56), a high level of serum Mn-SOD was noticed in the early stage as well as in the advanced stage of the disease. Immunoblot analysis confirmed the reactivity and specificity of the monoclonal antibody to the enzyme protein in the patients' sera. Immunostaining of a liver biopsy specimen from the patients with PBC revealed increased expression of the enzyme protein in damaged epithelial cells of interlobular bile ducts, bile ductules, and degenerated hepatocytes. These data suggested that free radicals including superoxide anion are possibly involved in the pathogenesis of the disease and Mn-SOD may play some role in a protection against the superoxide anion.
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PMID:Elevated level of serum Mn-superoxide dismutase in patients with primary biliary cirrhosis: possible involvement of free radicals in the pathogenesis in primary biliary cirrhosis. 168 6

The liver is an estrogen responsive organ. Clinically, estrogens may play a role in the induction of liver tumors and, experimentally, estrogens are involved in the control of hepatocyte proliferation. The results of a prospective controlled clinical trial using an anti-estrogen, tamoxifen, in patients with unresectable hepatocellular carcinoma (HCC) are presented below. Thirty-eight consecutive cirrhotics with HCC were allocated to either 30 mg/day tamoxifen or no treatment. The two groups of patients were matched for mean age, male/female ratio, Child-Pugh risk group, approximate tumor volume (US and/or CT scan) and etiology of the underlying cirrhosis. The drug appeared to have no side effects. Survival was significantly prolonged in tamoxifen-treated patients with 22% (vs. 5%) survival at 12 months. No differences were observed between males and females or alcoholic and non-alcoholic cirrhosis. In 53% of tamoxifen-treated patients the levels of alpha-fetoprotein dropped and, in this subgroup, survival was further prolonged. Tumor volume, lactate dehydrogenase (LDH) and alkaline phosphatase slowly increased, suggesting a slower, but continuous, progression of the disease. In conclusion, anti-estrogen treatment appears effective in the palliation of unresectable or otherwise untreatable HCC. A reduction in alpha-fetoprotein levels appears to be a favorable prognostic index.
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PMID:Unresectable hepatocellular carcinoma: a prospective controlled trial with tamoxifen. 170 74

Serum levels of alkaline phosphatase, gamma-glutamyltranspeptidase, -1 fucosidase and glutathione-S-transferase are increased in 60, 90, 75 and 64% of patients with hepatocellular carcinoma. In these patients the mean plasma fibrinogen levels is 461.78 mg/dl, while mean serum copper is 200.50 mg/dl. Serum levels of desgamma-carboxiprothrombin is over 900 mg/dl in 67% of the patients (60% of them have HB virus, mostly anti HBe positive). Forty to 95% of them have increased levels of -fetoprotein (AFP). The authors suggest that cirrhotic patients, with or without HB virus, specially those with increased AFP, should have ultrasound examination of the liver every 6 months. This method of imaging has been shown to be more sensitive than AFP (72% versus 25%) in the detection of hepatocellular carcinoma smaller than 2 cm in diameter.
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PMID:[Diagnosis of hepatocellular carcinoma performed by searching for serologic tumor markers]. 170 3

Serum CA 19-9 and alpha-fetoprotein (AFP) levels were determined in 211 patients with liver cirrhosis and 27 with primary hepatocellular carcinoma (HCC) associated with liver cirrhosis. This was done to determine the usefulness of CA 19-9 level with respect to AFP level in distinguishing between these two illnesses, and to assess the influence of some clinical and biochemical variables on these tests in patients with liver cirrhosis with or without primary HCC. Pathologic AFP values were found in 23 of 27 (sensitivity, 85%) patients with HCC; CA 19-9 levels increased in only 12 of 27 (sensitivity, 44%) HCC patients, the values being comparable with those of patients with liver cirrhosis. In liver cirrhosis a substantial number of false-positive values was found for both markers, although they were higher for CA 19-9 (50 of 211 versus 39 of 211). In liver cirrhosis correlations were found between AFP level and alanine amino-transferase level; and between CA 19-9 level and (1) total bilirubin value, (2) alkaline phosphatase level, and (3) pseudocholinesterase level. The authors conclude that CA 19-9 level is a poor biochemical marker, inferior to AFP level, in the detection of a carcinomatous transformation of liver cirrhosis. The finding of false-positive AFP values in liver cirrhosis seems mainly attributable to cellular proliferation and necrosis. Cholestasis seems to greatly affect serum CA 19-9 level variations, probably by reducing its liver metabolism.
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PMID:Serum CA 19-9 and alpha-fetoprotein levels in primary hepatocellular carcinoma and liver cirrhosis. 138 Dec 71

Serum alpha-fetoprotein (AFP) concentration was detected by use of 2 commercially available kits containing antibodies to human AFP--a radioimmunoassay and an enzymetric test. Using neonatal canine serum (a source high in AFP), it was determined that reagents from both kits were able to bind to canine AFP, but a significant difference was detected in AFP concentration. The enzymetric test was superior in detecting canine AFP. Sera from dogs were classified into 6 groups: from dogs with primary hepatic tumors only (group 1); from dogs with primary hepatic tumors and other tumors (group 2); from dogs with normal liver but with other types of neoplasia (group 3); from dogs with nonneoplastic hepatic disease and tumors originating in other organs (group 4); from dogs with nonneoplastic hepatic disease only (group 5); and from clinically normal dogs (group 6). Serum biochemical determinations (alkaline phosphatase, alanine transaminase, albumin, total protein, total bilirubin, and serum bile acids) and values from the 2 AFP assays were obtained for all dogs. Serum AFP concentration detected by the enzymetric test was significantly higher in dogs with hepatocellular carcinoma and cholangiocarcinoma. Values greater than 250 ng/ml were detected in 5 of 9 dogs with cholangiocarcinoma and in 3 of 4 dogs with hepatocellular carcinoma. High serum AFP concentration also was indicative of liver involvement in 2 of 3 dogs with primary hepatic lymphosarcoma; 2 dogs had values greater than 225 ng/ml. Serum AFP concentration in dogs with other types of hepatic tumors was less than 250 ng/ml, and serum AFP concentration could not be correlated with such tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of serum alpha-fetoprotein in dogs with hepatic tumors. 172 Jan 15


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