acid-phosphatase and Carcinoma--Hepatocellular

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Brain Neoplasms; Breast Neoplasms; Carcinoma, Hepatocellular; Catalase; DNA Nucleotidyltransferases; Fructose-Bisphosphate Aldolase; Glycine Hydroxymethyltransferase; Hexokinase; Hodgkin Disease; Intestinal Neoplasms; Isoenzymes; L-Lactate Dehydrogenase; Leukemia; Liver; Liver Neoplasms; Lung Neoplasms; Neoplasms; Pyruvate Kinase; Ribonucleotides; Sarcoma, Experimental; Stomach Neoplasms; Uridine Kinase

Topics: Acid Phosphatase; Alcohol Oxidoreductases; Aldehyde Oxidoreductases; Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; DNA Nucleotidyltransferases; Esterases; Fructose-Bisphosphatase; Fructose-Bisphosphate Aldolase; Glucosyltransferases; Glutaminase; Glycogen Synthase; Hexokinase; Humans; Isocitrate Dehydrogenase; Isoenzymes; L-Lactate Dehydrogenase; Liver Neoplasms; Malate Dehydrogenase; Mice; Neoplasms; Phosphotransferases; Pyruvate Kinase; Rats; Terminology as Topic; Thymidine Kinase; Transaminases; tRNA Methyltransferases; Uridine

Acid phosphatase type 6 (ACP6) is a mitochondrial lipid phosphate phosphatase that played a role in regulating lipid metabolism and there is still blank in the clinico-pathological significance and functional roles of ACP6 in human cancers. No investigations have been conducted on ACP6 in hepatocellular carcinoma (HCC) up to date.. Herein, we appraised the clinico-pathological significance of ACP6 in HCC via organizing expression profiles from globally multi-center microarrays and RNA-seq datasets. The molecular basis of ACP6 in HCC was explored through multidimensional analysis. We also carried out in vitro and in vivo experiment on nude mice to investigate the effect of knocking down ACP6 expression on biological functions of HCC cells, and to evaluate the expression variance of ACP6 in xenograft of HCC tissues before and after the treatment of NC.. ACP6 displayed significant overexpression in HCC samples (standard mean difference (SMD) = 0.69, 95% confidence interval (CI) = 0.56-0.83) and up-regulated ACP6 performed well in screening HCC samples from non-cancer liver samples. ACP6 expression was also remarkably correlated with clinical progression and worse overall survival of HCC patients. There were close links between ACP6 expression and immune cells including B cells, CD8 + T cells and naive CD4 + T cells. Co-expressed genes of ACP6 mainly participated in pathways including cytokine-cytokine receptor interaction, glucocorticoid receptor pathway and NABA proteoglycans. The proliferation and migration rate of HCC cells transfected with ACP6 siRNA was significantly suppressed compared with those transfected with negative control siRNA. ACP6 expression was significantly inhibited by nitidine chloride (NC) in xenograft HCC tissues.. ACP6 expression may serve as novel clinical biomarker indicating the clinical development of HCC and ACP6 might be potential target of anti-cancer effect by NC in HCC.

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Mice; Mice, Nude; RNA, Small Interfering

Therapeutic efficacy of conventional single PEGylated polymeric micelles is significantly reduced by limited endocytosis and intracellular drug release. To improve drug delivery efficiency, poly (ethylene glycol)-block-poly (l-lactic acid)/(Arg-Gly-Asp-Phe)-poly (aminoethyl ethylene phosphate)-block-poly (l-lactic acid) (PEG-PLLA/RGDF-PAEEP-PLLA) hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release are developed. The optimized hybrid micelles with 6 wt % of RGDF have favorable in vitro and in vivo activities. The hybrid micelles could temporarily shield the targeting efficacy of RGDF at pH 7.4 due to the steric effect exerted by concealment of RGDF peptides in the PEG corona, which strongly decreases the clearance by mononuclear phagocyte system and consequently improves the tumor accumulation. Inside the solid tumor with a lower acidic pH, the hybrid micelles restore the active tumor targeting property with exposed RGDF on the surface of the micelles because of the increased protonation and stretching degree of PAEEP blocks. RGDF-mediated endocytosis improves the tumor cell uptake. The hybrid micelles would also enhance intracellular drug release because of the hydrolysis of the acid/phosphatase-sensitivity of PAEEP blocks in endo/lysosome. Systemic administration of the hybrid micelles significantly inhibits tumor growth by 96% due to the integration of enhanced circulation time, tumor accumulation, cell uptake and intracellular drug release.

Topics: Acid Phosphatase; Animals; Antibiotics, Antineoplastic; Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Female; Humans; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Micelles; Polymers; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Tartrate-resistant acid phosphatase 5 (ACP5), which is essential for bone resorption and osteoclast differentiation, promotes cell motility through the modulation of focal adhesion kinase phosphorylation. However, whether ACP5 contributes to the metastasis and progression of hepatocellular carcinoma (HCC) remains unknown. In this paper, a complementary DNA microarray, serial deletion, site-directed mutagenesis and a chromatin immunoprecipitation assays confirmed that ACP5 is a direct transcriptional target of Forkhead box M1 (FoxM1). ACP5 expression was markedly higher in HCC tissues compared with adjacent noncancerous tissues. ACP5 overexpression was correlated with microvascular invasion, poor differentiation and higher tumor-node-metastasis stage. HCC patients with positive ACP5 expression had poorer prognoses than those with negative ACP5 expression. A multivariate analysis revealed that ACP5 expression was an independent and significant risk factor for disease recurrence and reduced-patient survival following curative resection. Transwell assays and an orthotopic metastatic model showed that the upregulation of ACP5 promoted HCC invasion and lung metastasis, whereas ACP5 knockdown inhibited these processes. The knockdown of ACP5 significantly attenuated FoxM1-enhanced invasion and lung metastasis. Immunohistochemistry revealed that ACP5 expression was positively correlated with FoxM1 expression in human HCC tissues, and their coexpression was associated with poor prognoses. In summary, ACP5 is a direct transcriptional and functional target of FoxM1. This novel FoxM1/ACP5 signaling pathway promotes HCC metastasis and may be a candidate biomarker for prognosis and a target for new therapies.

Topics: Acid Phosphatase; Adult; Carcinoma, Hepatocellular; Female; Forkhead Box Protein M1; Forkhead Transcription Factors; Humans; Isoenzymes; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Tartrate-Resistant Acid Phosphatase

The present study was designed to elucidate the involvement of acid phosphatase (ACP) in metastasis and lactate dehydrogenase (LDH) as an immediate compensatory alleviation mechanism for energy stress in liver lesions induced by hexachlorocyclohexane in Swiss mice. Animals were continuously exposed to hexachlorocyclohexane (500 ppm) for 2, 4, and 6 months. Neoplastic nodules and tumors developed after continuous exposure for 4 and 6 months, respectively. The distribution pattern of both enzymes markedly varied in neoplastic nodules and tumors. Intense ACP activity was more observed only in sinusoids and blood vessels of neoplastic nodule, whereas an overall increase in ACP activity was observed in the tumor. Noticeably, a significant decline in LDH activity was noted after 2 and 4 months of exposure, whereas LDH in a tumor region showed intense enzymatic activity. The role of acid phosphate in metastasis and LDH in oxidative stress during hepatocarcinogenesis induced by hexachlorocyclohexane has been discussed.

Topics: Acid Phosphatase; Animals; Carcinogens, Environmental; Carcinoma, Hepatocellular; Cell Nucleus Size; Cell Size; Disease Progression; Down-Regulation; Hexachlorocyclohexane; Hyperplasia; Insecticides; Lactate Dehydrogenases; Lipid Metabolism; Liver; Liver Neoplasms; Male; Mice; Neoplasm Proteins; Oxidative Stress; Up-Regulation

Chromosomal rearrangements unraveled by spectral karyotyping (SKY) indicated frequent chromosome 19 translocations in hepatocellular carcinoma (HCC). In an effort to characterize the aberrant 19 rearrangements in HCC, we performed positional mapping by fluorescence in-situ hybridization (FISH) in 10 HCC cell lines. SKY analysis indicated structural rearrangements of chromosome 19 in 6 cell lines, 4 of which demonstrated recurring 19p translocations with different partner chromosomes. Using fluorescence-labeled BAC probes, physical mapping indicated a breakpoint cluster between 19p13.12 and 19p12. A corresponding transcriptional mapping by cDNA array on 19p suggested the differential expression of a single downregulated gene ACP5 (tartrate-resistant acid phosphatase type 5). Quantitative RT-PCR confirmed the reduced expression of ACP5 and indicated a strong correlation of its repressed expression only in cell lines that contain a 19p rearrangement (p = 0.004). We further examined the expression of ACP5 in a cohort of 82 primary tumors and 74 matching nonmalignant liver tissues. In the primary HCC examined, a reduction of ACP5 transcripts by 2 to as much as 1,000-fold was suggested in 67% of tumors (55/82 cases). When compared to adjacent nonmalignant tissues, 46% of tumors (34/74 cases) demonstrated a lower expression level (p = 0.015). On closer examination, a high significance of ACP5 repression was suggested in the cirrhotic HCC subgroup that was derived from chronic hepatitis B infected patients (55%; 30/54 cases; p = 0.001). Functional examination of ACP5 ectopic expression in HCC cells further demonstrated a significant growth inhibitory effect of ACP5 on tumor cell survival (p < 0.001). In our study, the novel finding of common ACP5 downregulation in HCC may provide basis for further investigations on the role of acid phosphatase in hepatocarcinogenesis.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Hepatocellular; Chromosomes, Human, Pair 19; Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Isoenzymes; Karyotyping; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Tartrate-Resistant Acid Phosphatase; Translocation, Genetic; Tumor Cells, Cultured

Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption, but the mechanism responsible for tumor-mediated osteoclast activation has not yet been clarified. In the present study we utilized a well-known human breast cancer cell line (MDA-231) in order to assess its capability to influence osteoclastogenesis in human bone marrow cultures and bone resorption in fully differentiated osteoclasts. We demonstrated that conditioned medium (CM) harvested from MDA-231 increased the formation of multinucleated TRAP-positive cells in bone marrow cultures. Bone resorption activity of fully differentiated human osteoclasts and of osteoclast-like cell lines, from giant cell tumors of bone (GCT), was highly increased by the presence of MDA-231 CM. Moreover, while MDA-231 by themselves did not produce IL-6 tumor cell, CM increased the secretion of IL-6 by primary human osteoclasts and GCT cell lines compared to untreated controls. These data suggest that MDA-231 produce osteoclastic activating factor(s) that increase both osteoclast formation in bone marrow culture and bone resorption activity by mature cells. Moreover, breast cancer cells stimulate IL-6 secretion by osteoclasts that is one of the factors known to supports osteoclastogenesis.

Topics: Acid Phosphatase; Biomarkers; Bone Marrow Cells; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Carcinoma, Hepatocellular; Cell Differentiation; Cells, Cultured; Culture Media, Conditioned; Female; Giant Cell Tumors; Humans; Isoenzymes; Liver Neoplasms; Osteoclasts; Osteogenesis; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

Isoproterenol was used as a drug which, when administered in high doses, is able to induce lysosomal enzyme activity changes in in vivo conditions. We correlated lysosomal enzyme activity in the absence and presence of isoproterenol, obtained in whole animals and in HeLa and HepG2 cells in tissue culture. In vivo experiments: male Wistar rats (270-300 g) were treated subcutaneously with isoproterenol in various doses. Effect of isoproterenol on lysosomal enzyme activity was assayed in the heart after differential centrifugation. In vitro experiments: Isoproterenol in concentrations 0.1-100 microg/ml was added to HeLa and HepG2 cells and the activity of lysosomal enzyme was measured in the cell homogenate. In the sedimentable and nonsedimentable fractions of the rat myocardium, the isoproterenol-induced changes in the activity of lysosomal enzyme were time-and dose-dependent. In HeLa cells, isoproterenol administration caused a dose-dependent increase of lysosomal enzyme activity, while in HepG2 cells the activity remained unchanged. Thus the isoproterenol-induced changes in lysosomal enzyme activity in the rat myocardium were comparable with the results found in vitro in HeLa cells.

Topics: Acetylglucosaminidase; Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cathepsin D; Glucuronidase; Heart; HeLa Cells; Humans; Isoproterenol; Kinetics; Liver Neoplasms; Lysosomes; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Tumor Cells, Cultured

The expression of high- and low-molecular weight acid phosphatase (HMr- and LMr-AP) and zinc ion-dependent acid phosphatase (HMr-ZnAP and LMr-ZnAP) was compared in normal human liver and in Hep G2 human hepatocarcinoma cell line extracts. The investigation was carried out using Sephadex G-100 chromatography, molecular weight determination, and analysis of some distinctive biochemical characteristics and immunochemical properties. Normal human liver and Hep G2 cell lines expressed both HMr- and LMr-AP enzymes although in different proportions. HMr-ZnAP was detected only in human liver extract, while LMr-ZnAP was present only in hepatoma cell extract, indicating that they were differentially expressed in normal and transformed human liver cells.

Topics: Acid Phosphatase; Animals; Blotting, Western; Carcinoma, Hepatocellular; Cell Fractionation; Chlorides; Dextrans; Enzyme Activation; Gels; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Liver; Liver Neoplasms, Experimental; Nitrophenols; Organophosphorus Compounds; Tumor Cells, Cultured; Zinc Compounds

The dioxin receptor stimulates transcription of the cytochrome P-450IA1 gene in response to dioxin. Exposure of the intracellular dioxin receptor to dioxin leads to a rapid conversion of the receptor from a latent form to a DNA binding species which specifically recognizes dioxin-responsive positive control elements in vitro. In this report, we show that treatment of in vivo or in vitro ligand-activated receptor with potato acid phosphatase significantly reduced or abolished its specific DNA binding activity. This effect was inhibited in the presence of sodium phosphate. In control experiments, the ligand-activated glucocorticoid receptor was not inactivated by phosphatase treatment. Moreover, phosphatase treatment did not induce any detectable degradation of covalently labeled dioxin receptor, arguing against protease contamination as a cause for receptor inactivation. Finally, phosphatase-inactivated dioxin receptor exhibited bona fide levels of ligand binding activity. Taken together, these data suggest that phosphorylation may regulate the DNA binding activity of the ligand-occupied dioxin receptor.

Topics: Acid Phosphatase; Base Sequence; Carcinoma, Hepatocellular; Dioxins; DNA; DNA-Binding Proteins; Ligands; Molecular Sequence Data; Phosphorylation; Receptors, Aryl Hydrocarbon; Receptors, Drug; Transcription Factors; Tumor Cells, Cultured

We examined a series of hepatocellular neoplasms, including 4 adenomas, 7 hepatoblastomas, and 18 hepatocellular carcinomas (HCC) with enzyme histochemistry in plastic-embedded sections. Our most striking observation was that there was a distinct difference in the staining pattern for alkaline phosphatase (Alk0) in benign and malignant tumors. Non-neoplastic controls (normal liver, reactive lesions) and benign neoplasms showed a distinctive canalicular pattern of staining with Alk0. Malignant neoplasms, however, showed a virtual absence of Alk0 staining; 6 of 7 hepatoblastomas and 17 of 18 HCCs were practically devoid of staining, while the two positive cases showed a pattern easily discernible from normal. The sensitivity of the observed Alk0 staining pattern in detecting malignant hepatocellular neoplasms was 92% and the specificity was 100%. Cytoplasmic gamma-glutamyl-transferase (GGT) was present in a minority of HCCs, but faint staining was also seen in normal liver or in adenomas. It appears that these nonmorphologic techniques may aid the surgical pathologist in the differential diagnosis of primary hepatocellular neoplasms.

Topics: 5'-Nucleotidase; Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Carboxylic Ester Hydrolases; Carcinoma, Hepatocellular; gamma-Glutamyltransferase; Glucuronidase; Histocytochemistry; Humans; Liver Neoplasms; Naphthol AS D Esterase; Nucleotidases; Staining and Labeling

Tartrate-inhibitable acid phosphatase was purified to apparent homogeneity from human placenta. The enzyme is composed of two subunits with an apparent molecular mass of 48 kDa. Each subunit carries one oligosaccharide of the high-mannose/hybride type. The purified enzyme has an isoelectric point of pH 6.2. It cleaves phosphomonoester bonds at acid pH, is competitively inhibited by L-tartrate, Ki = 0.51 microM, and phosphate, Ki = 0.8mM. A monospecific antiserum raised against the purified placental enzyme precipitated 62% and 85% of the tartrate-inhibitable acid phosphatase present in extracts of placenta and fibroblasts, respectively. By means of subcellular fractionation and immunoprecipitation it was shown that the majority of tartrate-inhibitable acid phosphatase is located in lysosomes in normal and mucolipidosis II fibroblasts. In the human Hep G-2 hepatoma cells a significant fraction of the enzyme appears to be associated with non-lysosomal organelles.

Topics: Acid Phosphatase; Carcinoma, Hepatocellular; Cell Line; Electrophoresis, Polyacrylamide Gel; Female; Fibroblasts; Humans; Hydrolysis; Isoelectric Focusing; Liver Neoplasms; Placenta; Pregnancy; Subcellular Fractions; Tartrates

Serum activities of two lysosomal enzymes, beta-glucuronidase and acid phosphatase, were estimated in 66 patients with liver cell carcinoma, 10 with secondary liver cancer, 14 with cirrhosis of the liver, and 9 normal controls. A substantial increase in the enzyme activities was found in patients with liver cell carcinoma but not in those with secondary liver cancer. The degree of the enzyme elevations paralleled the stage of hepatoma. Although the serum activities of both enzymes were also elevated in patients with liver cirrhosis, the elevations were significantly higher in hepatoma than in liver cirrhosis. Possible mechanisms for the elevation of serum lysosomal enzyme activities in hepatoma are discussed, but further studies are necessary to elucidate the biological and clinicopathological significance of estimating serum lysosomal acid hydrolases in patients with primary liver cell carcinoma.

Topics: Acid Phosphatase; Adult; Aged; Alanine Transaminase; alpha-Fetoproteins; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Female; Glucuronidase; Hepatitis B Surface Antigens; Humans; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Lysosomes; Male; Middle Aged

Serum activities of lysosomal enzymes beta-glucuronidase and acid phosphatase were serially estimated in 14 patients with and without cirrhosis of the liver who underwent 40% to 80% hepatic resection. Substantial increases in enzyme activities were observed two to eight weeks after operation in ten of 11 patients who did not suffer from postoperative liver failure. Regeneration of the residual livers was almost satisfactory in all 11, as evidenced by clinical, roentgenologic, and histologic findings. In three patients with advanced cirrhosis who died of hepatic failure 21 to 39 days after extensive hepatic resection, there was neither the enzymatic reaction nor evidence of regeneration of the liver remnants. In the light of this study and our previous experimental studies, serial determination of the lysosomal enzyme activities in blood is probably a beneficial biochemical index for detection of progressive hepatic regeneration.

Topics: Acid Phosphatase; Adult; Aged; Carcinoma, Hepatocellular; Female; Glucuronidase; Hepatectomy; Humans; Liver Cirrhosis; Liver Function Tests; Liver Neoplasms; Liver Regeneration; Male; Middle Aged

An enzyme histochemical study was performed to investigate abnormal enzyme activity in human hepatocellular carcinoma (HCC) and, by application of these staining reactions to noncancerous liver disorders, to clarify the true nature of putative percancerous lesions. The enzyme activity of hepatocytes in cirrhotic livers, hepatitis B virus (HBV)-positive cells, and dysplastic liver cells was investigated. Although the tumor cells in HCC gave an intensively positive reaction for gamma-glutamyl transpeptidase activity at the cytoplasm and the whole-cell membrane, they were essentially deficient in glucose-6-phosphatase, alkaline phosphatase, acid phosphatase, and nonspecific esterase activities. Cirrhotic liver showed loss of the orderly zonal difference of enzyme activity that is present in normal liver. However, a pattern of enzyme deviation similar to that of HCC was not recognized anywhere. Neither HBV-positive hepatocytes nor dysplastic liver cells were shown enzymatically to be direct precusors of HCC.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Alkaline Phosphatase; Carcinoma, Hepatocellular; Cytoplasm; Female; gamma-Glutamyltransferase; Glucose-6-Phosphatase; Hepatitis B Surface Antigens; Humans; Liver; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Male; Middle Aged; Precancerous Conditions

Three enzymes in single cells were assayed dynamically by flow cytometry using four fluorogenic substrates. Acid phosphatase was determined with 7-bromo-3-hydroxy-2-naphtho-o-anisidine (naphthol AS-BI) phosphate and 4-methylumbelliferone (MU) phosphate, neutral esterase with fluorescein diacetate, and lactic dehydrogenase with NAD-sodium lactate. Fluorescence measurements obtained with the flow cytometer were converted into relative specific enzyme activities for single cells with molar fluorescence coefficients determined with a spectrofluorometer. Specific activities obtained from spectrofluorometric data were compared with activities calculated from flow cytometeric data. Flow cytometric assays gave lower specific single cell activities for 4-methylumbelliferone phosphate hydrolysis and for lactic dehydrogenase than did similar assays by standard spectrofluorometry. Product diffusion may be the greatest cause for this discrepancy.

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Line; Cricetinae; Cytological Techniques; Esterases; Female; Fluorescent Dyes; L-Lactate Dehydrogenase; Liver Neoplasms; Ovary; Spectrometry, Fluorescence

Intracellular localization of gallium-67 was investigated in Morris hepatoma-7316A and Shionogi mammary carcinoma-115 cells by the cell fractionation method 48 hr after an intraperitoneal injection of the nuclide. When lysosomes were purified from both tumors by discontinuous sucrose density gradient centrifugation, they had a strikingly high relative specific activity of the nuclide. From these results it was confirmed that gallium-67 is concentrated most specifically in the lysosomes of both tumor cells, which consist chiefly of phagolysosomes and can engulf only limited amount of foreign materials such as Triton and gallium-67.

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Fractionation; Gallium Radioisotopes; Liver Neoplasms; Lysosomes; Mammary Neoplasms, Experimental; Neoplasms, Experimental; Rats

Topics: Acid Phosphatase; Alcohol Oxidoreductases; Aminopterin; Animals; Bromodeoxyuridine; Carcinoma, Hepatocellular; Cell Division; Culture Techniques; DNA, Neoplasm; Liver Neoplasms; Malate Dehydrogenase; Ornithine Decarboxylase; Rats; Thymidine; Thymidine Monophosphate; Tyrosine Transaminase

The lysosomes of both Novikoff heptoma and liver from Novikoff heptoma-bearing rats were found to be relatively intact structurally, lower in acid phosphatase activity, greatly depleted in number but with nearly normal membrane integrity when compared with normal liver.

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Liver; Liver Neoplasms; Lysosomes; Male; Neoplasms, Experimental; Permeability; Rats

In cells of ascites Zajdela hepatoma in different terms after irradiation of the abdominal region in tumor-bearing rats (doses of 500, 700 and 1000 rad) there were found a reduction of highly active and an increase of insignificantly active normal isoenzymes of lactate dehydrogenase and also disorders in the content of acid phosphatase.

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Isoenzymes; L-Lactate Dehydrogenase; Liver Neoplasms; Neoplasms, Experimental; Rats

Mitochondria were isolated from Morris hepatomas with rapid (types 3683, 7777, and 3924A) and intermediate (types 5123D and 7800) growth rates, using proteolytic digestion of minced tumor tissue to release the particles. Mitochondria isolated by the same procedure from rat liver were employed as controls. All the hepatoma mitochondria were capable of coupled respiration with normal phosphorylation yields (ADP/O) and respiratory control ratios ranging from 2 to considerably more than 10. Particles from hepatomas 7777 and 7800 exhibited properties closest to liver mitochondria, while those from hepatomas 3683 and 3924A showed the greatest difference. All the hepatoma mitochondria were capable of oxidizing succinate, 3-hydroxybutyrate and monoamines. However, the oxidation rates of the latter two substrates by mitochondria from hepatomas 3683 and 3924A were only a fraction of the control rates. These differences appeared to be due, at least in part, to the structural instability of the isolated hepatoma mitochondria. In contrast to the reports of others, all hepatoma mitochondria exhibited considerable stimulation of ATPase activity by uncouplers. Maximal stimulation of ATPase activity by representatives of three classes of uncouplers was in all instances comparable to the values obtained for rat liver mitochondria.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Carcinoma, Hepatocellular; Dinitrophenols; Hydroxybutyrate Dehydrogenase; Liver Neoplasms; Mitochondria; Mitochondria, Liver; Monoamine Oxidase; Neoplasms, Experimental; Oxidative Phosphorylation; Oxygen Consumption; Rats; Rutamycin

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Esterases; Isoenzymes; Liver Neoplasms; Mice; Neoplasms, Experimental; o-Aminoazotoluene

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Carcinoma, Hepatocellular; Electron Transport Complex IV; Glucosephosphate Dehydrogenase; Humans; Liver Neoplasms; Male; Middle Aged; Oxidoreductases; Peroxidases; Phosphoric Monoester Hydrolases; Succinate Dehydrogenase

Rats bearing Reuber H-35 or Novikoff hepatomas and mice bearing L1210 or L5178Y murine leukemias exhibited elevated serum levels of fetuin : N-acetylneuraminic acid transferase (EC 2.4.99.1) activity. The serum transferase activity could be correlated with the growth rate of the tumor; in animals bearing the more rapidly growing Novikoff hepatoma, activity was higher than in animals bearing the Reuber H-35 hepatoma. Higher transferase levels were also found in L1210 leukemic mice than in mice with the slightly slower growing L5178Y leukemia. Serum from rats bearing Reuber H-35 hepatoma and mice bearing L1210 murine leukemia had elevated levels of alpha- and beta-glucosidase (EC 3.2.1.20 and EC 3.2.1.21), alpha- and beta-galactosidase (EC 3.2.1.22 and (3.2.1.23), beta mannosidase (EC 3.2.1.25), alpha- and beta-fucosidase (EC 3.2.1.- and EC 3.2.1.38), beta-N-acetylglucosaminidase (EC 3.2.1.30) and acid phosphatase (EC 3.1.3.2); alpha-mannosidase (EC 3.2.1.24), beta-N-acetylgalactosaminidase (EC 3.2.2.-) and beta-xylosidase (EC 3.2.1.37) were not elevated. In animals bearing Reuber H-35 hepatoma, host liver levels of glycosidases, beta-glucuronidase (EC 3.2.1.31) and acid phosphatase were elevated over both the control and the hepatoma values. The data are interpreted to mean that the tumors or various host tissues release large quantities of enzymes into the serum and that enzyme levels in host organs may also be affected by the tumor.

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Female; Glycoside Hydrolases; Leukemia L1210; Leukemia, Experimental; Liver; Liver Neoplasms; Lysosomes; Male; Mice; Mice, Inbred DBA; Mice, Inbred Strains; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Rats, Inbred ACI; Sialyltransferases; Transferases; Transplantation, Homologous

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Fractionation; D-Amino-Acid Oxidase; Electron Transport Complex IV; Glucose-6-Phosphatase; L-Lactate Dehydrogenase; Liver; Liver Neoplasms; Male; Microscopy, Electron; Mitochondria, Liver; Monoamine Oxidase; Morphinans; Neoplasms, Experimental; Ornithine; Oxidoreductases; Oxidoreductases, N-Demethylating; Phosphoric Monoester Hydrolases; Rats; Subcellular Fractions; Transaminases

Topics: Acid Phosphatase; Aminopeptidases; Animals; Antigens; Carcinoma, Hepatocellular; Cell Membrane; Esterases; Fetus; Glutamates; Leucine; Liver; Liver Neoplasms; Microsomes, Liver; NADH, NADPH Oxidoreductases; Neoplasms, Experimental; p-Dimethylaminoazobenzene; Phosphoric Monoester Hydrolases; Rats; Tetrazoles

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Fractionation; Cells, Cultured; Cycloheximide; Dactinomycin; Deoxyribonucleases; Fibroblasts; Glucuronidase; HeLa Cells; Humans; Liver; Liver Neoplasms; Mice; Neoplasms, Experimental; Rats; Ribonucleases

Topics: Acid Phosphatase; Adenosine Diphosphate; Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Antibodies, Neoplasm; Carcinoma, Hepatocellular; Catalase; Detergents; Electron Transport; Hydroxylation; Immunodiffusion; Immunoelectrophoresis; In Vitro Techniques; Liver; Liver Neoplasms; Membranes; Neoplasms, Experimental; Nucleosides; Phosphoric Monoester Hydrolases; Precipitins; Rabbits; Rats; Solubility

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Cells; Cells, Cultured; Chromatography, DEAE-Cellulose; Drug Stability; Fibroblasts; Hydrogen-Ion Concentration; Liver; Liver Neoplasms; Mice; Rats; Subcellular Fractions; Temperature; Thymus Gland

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Fractionation; Centrifugation, Density Gradient; Centrifugation, Zonal; Electron Transport Complex IV; Gallium; In Vitro Techniques; Liver; Liver Neoplasms; Lysosomes; Male; Methods; Microsomes, Liver; Particle Size; Proteins; Radioisotopes; Rats

Topics: Acid Phosphatase; Animals; Autoradiography; Carcinoma, Hepatocellular; Centrifugation, Density Gradient; Centrifugation, Zonal; Female; Gallium; Hexosaminidases; Liver Neoplasms; Lymphoma, Non-Hodgkin; Lysosomes; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Radioisotopes; Rats

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Membrane; Copper; Drug Stability; Edetic Acid; Gangliosides; Glucuronidase; Glycosides; Hydrogen-Ion Concentration; Kinetics; Lactose; Lithium; Liver; Liver Neoplasms; Lysosomes; Male; Microscopy, Electron; Neoplasms, Experimental; Neuraminidase; Rats; Spectrophotometry

The effect of dexamethasone on adenosine 3',5'-monophosphate (cAMP) phosphodiesterase activity in cultured HTC hepatoma cells was investigated. Homogenates of these cells contain phosphodiesterase activity with two apparent Michaelis constants for cAMP (2-5 mum and 50 mum). At all substrate concentrations tested, phosphodiesterase activity was decreased 25-40% in cells incubated for 36 hr or more with 1 mum dexamethasone. Acid phosphatase activity in the same cells was not decreased. alpha-Methyl testosterone, 1 mum, was without effect on phosphodiesterase activity. Incubation for 10 min with epinephrine plus theophylline increased the cAMP content of the HTC cells 3- to 6-fold. In cells incubated for 72 hr with dexamethasone, the basal concentration of cAMP was slightly increased and the increment produced by epinephrine plus theophylline was markedly increased. We believe that in many cells the so-called permissive effects of steroid hormones on cAMP mediated processes may be due to an effect of these hormones on cAMP phosphodiesterase activity similar to that observed in HTC cells incubated with dexamethasone.

Topics: Acid Phosphatase; Carcinoma, Hepatocellular; Cells, Cultured; Cyclic AMP; Dexamethasone; Epinephrine; Kinetics; Liver Neoplasms; Methyltestosterone; Phosphodiesterase Inhibitors; Phosphoric Monoester Hydrolases; Theophylline; Tritium

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Liver; Liver Neoplasms; Lysosomes; Mice; Mice, Inbred Strains; Microscopy, Electron; Neoplasms, Experimental

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Electrophoresis; Esterases; Glucose-6-Phosphatase; Isoenzymes; Liver; Liver Neoplasms; Male; Microscopy, Electron; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Experimental; Rats

Topics: Acid Phosphatase; Alanine Transaminase; Alkaline Phosphatase; Animals; Ascitic Fluid; Carcinoma, Hepatocellular; Cathepsins; Female; Glucuronidase; Glycoside Hydrolases; Hyaluronoglucosaminidase; Liver Neoplasms; Lysosomes; Mitochondria, Liver; Neoplasms, Experimental; Podophyllin; Rats

Topics: Acetates; Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cathepsins; Cells, Cultured; Cortisone; Female; Freezing; Glycoside Hydrolases; Hexosaminidases; Kinetics; Liver; Liver Neoplasms; Lysosomes; Neoplasms, Experimental; Rats; Surface-Active Agents; Tyrosine Transaminase

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Digitalis Glycosides; Enzyme Activation; Glucuronidase; Hot Temperature; Hydrogen-Ion Concentration; Hypotonic Solutions; Liver Neoplasms; Lysosomes; Neoplasms, Experimental; Phospholipases; Polycyclic Compounds; Rats; Trypsin

Topics: Acid Phosphatase; Adult; Albumins; Bile Acids and Salts; Carcinoma, Hepatocellular; Esterases; Fibrinogen; Glycogen; Histocytochemistry; Humans; Hydroxyindoleacetic Acid; Lipids; Lipoproteins; Liver Neoplasms; Lung Neoplasms; Male; Malignant Carcinoid Syndrome; Microscopy, Electron; Peroxidases; Serotonin; Staining and Labeling; Transferrin

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cytosine Nucleotides; Golgi Apparatus; Histocytochemistry; Liver Neoplasms; Lysosomes; Microscopy; Microscopy, Electron; Neoplasms, Experimental; Rats; Staining and Labeling

Topics: Acid Phosphatase; Adenosine Triphosphatases; Aged; Alkaline Phosphatase; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Glucose-6-Phosphatase; Glucosephosphate Dehydrogenase; Histocytochemistry; Humans; Liver Neoplasms; Male; Microscopy, Electron; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Carcinogens; Carcinoma, Hepatocellular; Fluorenes; Glucose-6-Phosphatase; Glucuronidase; Glycogen; Histocytochemistry; Hyperplasia; L-Lactate Dehydrogenase; Liver Diseases; Liver Neoplasms; Male; Neoplasms, Experimental; Phosphorylase Kinase; Rats; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Liver Neoplasms; Mice; Neoplasms, Experimental; Radiation Effects; Rats

Topics: Acid Phosphatase; Aflatoxins; Aminopyrine; Animals; Anisoles; Benzopyrenes; Carcinoma, Hepatocellular; Diet; Dimethyl Sulfoxide; Glucose-6-Phosphatase; Injections, Intraperitoneal; Intubation, Gastrointestinal; Liver; Liver Neoplasms; Male; Microsomes, Liver; Mixed Function Oxygenases; Nitroso Compounds; Oxidoreductases; Rats; Thymidine; Transferases; Tritium; Vitamin K

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Cathepsins; Deoxyribonucleases; Galactosidases; Glucosephosphate Dehydrogenase; Glucuronidase; Hydrolases; In Vitro Techniques; Liver; Liver Neoplasms; Lysosomes; Malate Dehydrogenase; Neoplasms, Experimental; Oxidoreductases; Phosphogluconate Dehydrogenase; Rats; Ribonucleases; Succinate Dehydrogenase; Sulfatases

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bile Ducts; Biliary Tract Diseases; Bone and Bones; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; Chromatography, Gel; Chromatography, Ion Exchange; Electrophoresis; Intestines; Isoenzymes; Kidney; Ligation; Liver; Liver Diseases; Liver Neoplasms; Male; Neoplasms, Experimental; Rats

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Calcium; Carcinogens; Carcinoma, Hepatocellular; Castration; Cell Membrane; Cholesterol; Edetic Acid; Estrone; Female; Glycerophosphates; Liver; Liver Neoplasms; Magnesium; Male; Neoplasms, Experimental; Nitrophenols; Phenobarbital; Potassium; Rats; Sex Factors; Testosterone; Zinc

Growth of cultured rat hepatoma cells in the presence of 5-bromodeoxyuridine results in a rapid inhibition of the synthesis of adrenal steroid-inducible tyrosine aminotransferase (EC 2.6.1.5) and slower decreases in the concentrations of lactate dehydrogenase (EC 1.1.1.27), alcohol dehydrogenase (EC.1.1.1.1), and glucose-6-phosphate dehydrogenase (EC 1.1.1.49). During the same period, neither overall cell growth nor the concentrations of malate dehydrogenase (EC 1.1.1.37), acid phosphatase (EC 3.1.3.2), or alanine aminotransferase (EC 2.6.1.2) were significantly decreased by the base analog. Addition of thymidine to the growth medium rapidly counteracts the inhibition of tyrosine aminotransferase synthesis but restores the normal concentrations of lactate-, alcohol-, and glucose-6-phosphate dehydrogenases much more slowly. Growth of the cells for only one generation in the presence of bromodeoxyuridine, followed by the addition of thymidine, produces transient decreases in the concentrations of the three "late-responding" dehydrogenases, beginning 2-3 generations after exposure to the analog.It is concluded that the selective inhibitory effects of the analog could result from a mechanism in which bromodeoxyuridine is uniformly incorporated into cellular DNA, but inhibits the transcription of only certain genes into messenger RNA. A mathematical model is derived to account for the observed differences in the kinetics of the inhibition of synthesis of the gene products that are sensitive to the analog.

Topics: Acid Phosphatase; Alanine Transaminase; Alcohol Oxidoreductases; Animals; Bromodeoxyuridine; Carcinoma, Hepatocellular; Cell Division; Cells, Cultured; Glucosephosphate Dehydrogenase; Kinetics; L-Lactate Dehydrogenase; Liver Neoplasms; Rats; Thymidine; Time Factors; Tyrosine Transaminase

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Nucleus; Dactinomycin; Deoxyribonucleases; Histocytochemistry; In Vitro Techniques; Kidney; Liver; Liver Neoplasms; Membranes; Methods; Microscopy, Electron; Neoplasms, Experimental; Pancreas; Polyvinyls; Rats; Ribonucleases; Sex Chromatin

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Galactosidases; Glycoside Hydrolases; Liver; Liver Neoplasms; Lysosomes; Mitochondria, Liver; Neoplasms, Experimental; Rats; Specific Gravity

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cathepsins; Galactosidases; Hydrolases; Liver; Liver Neoplasms; Neoplasm Transplantation; Neoplasms, Experimental; p-Dimethylaminoazobenzene; Rats; Sulfatases

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Centrifugation; Deoxyribonucleases; Hydrolases; Liver Neoplasms; Lysosomes; Mitochondria, Liver; Neoplasms, Experimental; Rats

Topics: Acid Phosphatase; Animals; Ascites; Carcinoma, Hepatocellular; Cell Line; Cytoplasm; Glycogen; Histocytochemistry; Liver; Liver Neoplasms; Lysosomes; Microscopy, Electron; Neoplasms, Experimental; Rats

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Liver Neoplasms; Microsomes; Rats

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cell Nucleus; Deoxyribonucleases; Histocytochemistry; Hydrogen-Ion Concentration; Hyperplasia; Liver; Liver Neoplasms; Liver Regeneration; Male; Methods; Neoplasms, Experimental; p-Dimethylaminoazobenzene; Rats

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bilirubin; Biopsy; Blood Cell Count; Blood Protein Disorders; Blood Protein Electrophoresis; Blood Sedimentation; Bone Marrow Examination; Carcinoma, Hepatocellular; Cholesterol; Hepatitis; Humans; Immunoelectrophoresis; Immunoglobulin G; Liver Cirrhosis; Liver Neoplasms; Male; Neoplasm Metastasis; Phosphates; Transaminases

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Catalase; Cathepsins; Cell Nucleus; Centrifugation, Density Gradient; Electron Transport Complex IV; Galactosidases; Glucose-6-Phosphatase; Hydrolases; Liver; Liver Neoplasms; Microsomes, Liver; Mitochondria, Liver; Neoplasm Transplantation; Rats; Ribonucleases

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Catalase; Cathepsins; Centrifugation, Density Gradient; Electron Transport Complex IV; Glucose-6-Phosphatase; Glycogen; Hydrolases; Liver; Liver Neoplasms; Microsomes, Liver; Mitochondria, Liver; Rats; Ribonucleases; Sucrose

Topics: Acid Phosphatase; Animals; Carcinoma, Hepatocellular; Cathepsins; Centrifugation, Density Gradient; Electron Transport Complex IV; Iodine Isotopes; Liver Neoplasms; Lysosomes; Mitochondria, Liver; Rats; Surface-Active Agents

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinoma, Hepatocellular; Edetic Acid; Electrophoresis; In Vitro Techniques; Liver Neoplasms; Neoplasm Transplantation; Neoplasms, Experimental; Neuraminidase; Rats; Trypsin

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Arginase; Carcinoma, Hepatocellular; Deoxyribonucleases; Glucose-6-Phosphatase; Glucosephosphate Dehydrogenase; Glutathione Reductase; Isoenzymes; L-Lactate Dehydrogenase; Liver Neoplasms; Male; Mitosis; Neoplasms, Experimental; Nitrogen Mustard Compounds; Phosphoric Monoester Hydrolases; Radiation Effects; Rats; Sulfhydryl Compounds

Topics: Acid Phosphatase; Animals; Carcinogens; Carcinoma, Hepatocellular; Cell Membrane; Cell Nucleus; Endoplasmic Reticulum; Fluorenes; Golgi Apparatus; Liver Neoplasms; Male; Microscopy, Electron; Microsomes; Mitochondria; Neoplasms, Experimental; Rats

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carcinogens; Carcinoma, Hepatocellular; Cats; Guinea Pigs; Liver; Liver Neoplasms; Methods; Mice; Neoplasms, Experimental; Precancerous Conditions; Rabbits; Rats; Time Factors

Topics: Acid Phosphatase; Carcinoma, Hepatocellular; Cell Membrane Permeability; Chromatography; Edetic Acid; Electrophoresis; Esterases; Histones; L-Lactate Dehydrogenase; Liver; Liver Neoplasms; Neoplasm Proteins; Neoplasms; Neoplasms, Experimental; p-Dimethylaminoazobenzene; Proteins; Rats; Research; Tissue Culture Techniques