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)

Type IV collagen-degrading enzyme activity was measured in liver homogenate obtained from 10 patients with hepatocellular carcinomas. Type IV collagen, the enzyme substrate, was extracted from human placenta with pepsin digestion, and labeled with [1-14C] acetic anhydride. The homogenate was preincubated with p-aminophenylmercuric acetate to activate the latent form of the enzyme, and then the enzyme activity was measured at pH 7.5 by adding a substrate mixture. Referring to previous reports, the enzyme measured seemed to be a neutral metalloprotease. The enzyme activity of the homogenate was markedly reduced by omitting the p-aminophenylmercuric acetate pretreatment, indicating that the enzyme was present mainly in the latent form. The activity seemed to be higher in the peripheral portion of hepatocellular carcinoma than in the center. Further the activity was found to be the highest in a hepatocellular carcinoma patient with many metastatic nodules in the lung. The results might suggest that type IV collagen-degrading enzyme participates in tumor invasion and intrahepatic or remote metastasis.
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PMID:Type IV collagen-degrading enzyme activity in hepatocellular carcinoma. 301 67

Activity of neutral protease was increased in sera of rats bearing ascites hepatoma AH109A compared to those of normal rats. The protease was isolated from serum protein and partially purified approximately 1,150 times in specific activity after sequential column chromatography of hemoglobin affinity, lysine-Sepharose, Ultrogel AcA34 and TSK-gel G2000SW in that order. The protease fraction still seemed to contain at least two kinds of proteases, serine and cysteine protease. It had a molecular weight of 18-21 kilodaltons with broad optimal pH range of 7.0-9.0, maximum at 8.0. Intradermal injection of the crude preparation of the neutral protease fraction induced extravascular emigration of circulating tumor cells in vivo. Moreover, partially purified protease degraded pepsin-treated chains of bovine glomerular type IV collagen in vitro, but such an in vitro action of the protease was inhibited by an addition of soybean trypsin inhibitor or mercuric chloride. It failed to cleave salt-extracted rat skin type I collagen under the same digestive conditions for bovine type IV collagen. The serum neutral proteases of tumor-bearing host may play some cooperative roles during extravascular emigration of tumor cells by destruction of vascular basement membrane.
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PMID:Partial purification and characterization of serum protease from tumor-bearing rats which cleaves type IV collagen. 353 Oct 79

Vaccine against human hepatitis B was prepared using antigen derived from hepatitis B carrier hepatoma cells grown in the interstices of a Diaflo hollow filter unit. Hepatitis B surface antigen (HBsAg) produced by these cells was purified by immune affinity chromatography, digestion with DNase and pepsin, and Sephadex G-150 separation. The Formalin-treated antigen was formulated in 20-micrograms dose on alum adjuvant with thimerosal added as a preservative. This cell culture vaccine was as potent as human plasma-derived vaccine as measured in a mouse potency assay. The vaccine proved safe in tests in chimpanzees and in human subjects who were in late stages of cancer of the central nervous system and who were receiving therapy for their condition. None of five subjects who received the vaccine developed untoward clinical reactions. Two of the subjects who received all three doses of vaccine developed antibody against HBsAg. Three persons, two given only the primary doses and one who was given all three doses but was lost to follow-up, demonstrated no response. The slow and relatively low antibody responses to the vaccine were similar to those in other immunosuppressed persons who were given vaccine of human plasma origin.
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PMID:Vaccine against human hepatitis B virus prepared from antigen derived from human hepatoma cells in culture. 632 Feb 12

Bivariate flow cytometric analysis of p53 protein and DNA content was studied in archival specimens of hepatocellular carcinoma (HCC) from Chinese patients and corresponding benign liver tissues from a series of 51 patients at Sun Yat-sen University of Medical Sciences. Extracted nuclei were stained with the fluoresceinated monoclonal antibody PAb 1801, which recognizes human p53 protein (mutant and wild types). The nuclei were counterstained with the DNA stain propidium iodide. They were measured on an Ortho FC-200 flow cytometer and the data acquired and analyzed with an IBM 386 personal computer using Kusuda's Get Simple and List Simple software. Of the 51 hepatomas studied, 26 (51%) were p53 positive as compared with 4 (16%) of 24 samples of benign liver tissue from the same patients (P < .0257). The S-phase fraction of p53-positive HCC (12.3 +/- 8.8%) (SD) was significantly greater (P < .05) than for p53-negative HCC (7.4 +/- 7.2%). p53 Expression did not correlate with age, sex, alpha-fetoprotein, hepatitis B surface antigen, tumor size, tumor grade or survival rate. List Simple software permitted analysis of each specimen together with its isotype control (IgG1) on the same cytogram so that p53 expression could be determined separately for the diploid and aneuploid populations of aneuploid tumors and for tumor cells of diploid tumors in the various phases of the cell cycle. Since p53 (PAb 1801) expression can withstand formalin fixation and pepsin treatment of paraffin-embedded tissues, flow cytometric analysis of archival specimens is feasible, and clinical correlations such as these may be carried out in retrospective studies of other tumors.
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PMID:Bivariate flow cytometric analysis of p53 and DNA content in hepatocellular carcinoma. 804 59

The asparagine-linked sugar chains in serum transferrin purified from patients with hepatocellular carcinoma (n = 13), healthy individuals (n = 5) and patients with liver cirrhosis (n = 6) were compared. Sugar chains released with N-glycanase from desialylated and pepsin-digested transferrin were derivatized by reductive pyridylamination. Analysis of the sugar chains by high performance liquid chromatography in combination with exoglycosidase digestion revealed an increase of a biantennary complex-type sugar chain with a fucosylated trimannosyl core; Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3) Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc in 7 of 13 cancer patients and an increase of a sugar chain with a fucosylated trimannosyl core and bisecting N-acetylglucosamine; Gal beta 1-4GlcNAc beta 1-2Man alpha 1-6(GlcNAc beta 1-4) (Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc in one of the 13 cancer patients. Further, the fucosylated alteration of the sugar chain was detected also in alpha 1-antitrypsin, hemopexin, alpha 1-acid glycoprotein and alpha 2-HS glycoprotein from one of the patients with increased fucosylated transferrin.
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PMID:Alteration of asparagine-linked glycosylation in serum transferrin of patients with hepatocellular carcinoma. 817 73

Plasma and ascitic fluid of rats bearing the Yoshida ascites hepatoma AH-130 were shown to contain high levels of proteolytic enzymes belonging to different classes active at neutral and acidic pH. Relative to those measured in control rat plasma, in tumor-bearing animals, the activity levels of lysosomal cathepsins B and L, in their latent, acidic-activatable form, were approximately 5-fold higher in plasma and 9-fold higher in ascitic fluid, and cathepsin D activity was about 5-fold higher in both plasma and ascitic fluid. Plasma and ascitic fluid of tumor-bearing rats also contained novel neutral and acidic gelatinolytic activities. The latter, as revealed by zymographic analysis conducted at pH 6.0, in the presence of dithiothreitol and in the absence of divalent metal ions, was sensitive to iodoacetamide inhibition but not to EDTA, showed a molecular mass of approximately 90 kD on SDS-PAGE, and was lost upon limited proteolysis with pepsin. Therefore, this enzyme is not identifiable as cathepsin B or L or their related latent forms and may represent a novel, so far undescribed, gelatinase. Its presence exclusively in the body fluids of AH-130-bearing rats suggests its possible use as a tumor marker.
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PMID:High levels of proteolytic enzymes in the ascitic fluid and plasma of rats bearing the Yoshida AH-130 hepatoma. 862 Dec 67

Ki-67 antigen was visualized in formalin-fixed, paraffin-embedded liver biopsy specimens using monoclonal antibody to Mib-1 to identify the proliferating hepatocytes. Thirty liver specimens obtained from 10 patients with chronic hepatitis (CH) or liver cirrhosis (LC) and 10 patients with hepatocellular carcinoma were studied. Liver specimens were treated with a pepsin solution or heated with autoclave or treated with microwave as a part of antigen retrieval system; then stained with an immunoperoxidase method using a monoclonal antibody to Ki-67 (Mib-1). Stable stainings were obtained in the sections treated with autoclave. Ki-67 was detected in the nuclei of hepatocytes, bile duct epithelium, fibroblast and infiltrating mononuclear cells. In patients with CH and LC, the numbers of hepatocytes positive for Ki-67 has a good co-relation with serum GPT level (p < 0.01), while has no relationship with the degree of fibrosis. The number of hepatocytes positive for Ki-67 has a good co-relation with the degree of the differentiation of hepatocellular carcinoma. Detection of proliferating hepatocytes using Mib-1 is useful to understand the degree of proliferation.
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PMID:[Detection of Ki-67 in liver biopsy specimens using monoclonal antibody to Mib-1]. 1059 Jun 70

The genes encoding alpha 1-antitrypsin (alpha 1AT, gene symbol P I) and corticosteroid-binding globulin (CBG) are part of a cluster of serine protease inhibitor (serpin) genes on human chromosome 14q32.1. Both genes are highly expressed in the liver and in cultured hepatoma cells, and the approximately 100-kb region around these genes contains an extensive array of expression-associated DNase I-hypersensitive sites (DHSs). Activation of human alpha 1AT and CBG transcription occurred when human chromosome 14 was transferred from nonexpressing cells to rat hepatoma cells. This activation event was accompanied by long-range chromatin reorganization of the entire region and the de novo formation of 17 expression-associated DHSs. Both gene activation and chromatin remodeling in hepatic cells required the liver-enriched transactivators hepatocyte nuclear factors-1 alpha and -4 (HNF-1 alpha and HNF-4). In this study, we tested whether ectopic expression of HNF-1 alpha and HNF-4 in nonexpressing cells could activate alpha 1AT and/or CBG transcription, and we monitored the chromatin structure of the locus in stably transfected fibroblasts. We report that both alpha 1AT and CBG mRNAs were expressed in fibroblast transfectants that stably expressed HNF-1 alpha and HNF-4, but expression was only approximately 1-10% of that observed in hepatic cells. Gene activation in these cells was accompanied by partial chromatin remodeling, as 6 of 17 expression-associated DHSs were formed. The potential implications of these results are discussed.
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PMID:Partial activation of gene activity and chromatin remodeling of the human 14q32.1 serpin gene cluster by HNF-1 alpha and HNF-4 in fibroblast microcell hybrids. 1158 88

Antifungal peptides with a molecular mass of 9 kDa and an N-terminal sequence demonstrating remarkable similarity to those of nonspecific lipid transfer proteins (nsLTPs) were isolated from seeds of the vegetable Brassica campestris and the mung bean. The purified peptides exerted an inhibitory action on mycelial growth in various fungal species. The antifungal activity of Brassica and mung bean nsLTPs were thermostable, pH-stable, and stable after treatment with pepsin and trypsin. In contrast, the antifungal activity of mung bean chitinase was much less stable to changes in pH and temperature. Brassica LTP inhibited proliferation of hepatoma Hep G2 cells and breast cancer MCF 7 cells with an IC(50) of 5.8 and 1.6 microM, respectively, and the activity of HIV-1 reverse transcriptase with an IC(50) of 4 microM. However, mung bean LTP and chitinase were devoid of antiproliferative and HIV-1 reverse transcriptase inhibitory activities. In contrast to the mung bean LTP, which exhibited antibacterial activity, Brassica LTP was inactive. All three antifungal peptides lacked mitogenic activity toward splenocytes. These results indicate that the two LTPs have more desirable activities than the chitinase and that there is a dissociation between the antifungal and other activities of these antifungal proteins.
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PMID:Lipid transfer proteins from Brassica campestris and mung bean surpass mung bean chitinase in exploitability. 1772 19

Five fluorouracil (5-FU) is extensively used in the treatment of hepatocellular carcinoma (HCC). It is well documented that 5-FU and its metabolites inhibit DNA synthesis through inhibition of thymidylate synthetase. Little is known about additional pathways for 5-FU in managing HCC. The present experiment was mainly designed to study possible biochemical pathways that can be added to 5-FU's mechanisms of action. Four groups of rats constituted a control group (given saline only), a trichloroacetic acid group (TCA, 0.5 g/kg/day for 5 days, orally), a 5-FU-positive group (75 mg/kg body weight, intraperitoneally, once weekly for 3 weeks) and a TCA-treated with 5-FU group (24 h from last TCA dose). We executed both biochemical-serum alpha-fetoprotein (AFP), liver tissue contents of total glycosaminoglycan (TGAGs), collagen (represented as hydroxyproline), total sialic acid (TSA), free glucosamine (FGA) and proteolytic enzyme activity (as pepsin and free cathepsin-D-and histological examinations of the liver tissue. The results revealed histological changes such as central vein congestion and irregularly shaped, substantially enlarged, vesiculated and binucleated hepatocytes. The nuclei were mostly polymorphic and hyperchromatic, and several vacuolation was noticed in the cytoplasm encircling the nucleus with masses of acidophilic material. 5-FU greatly corrected these changes, except that some necrotic and cytotoxic effects of 5-FU were still shown. AFP was significantly elevated in TCA-intoxicated, but reversed in 5-FU-treated, groups. Increased proteolytic activity by TCA was reversed by 5-FU, which also restored TGAG contents to normal; but both TCA and 5-FU depleted collagen content. TCA significantly elevated FGA but depressed TSA; this action was reversed by 5-FU treatment. In conclusion, it is possible that proteolytic activity, expressed as upregulated pepsin and free cathepsin-D activities, is increased in HCC. This is accompanied by extracellular matrix macromolecular disturbance, manifested as decreased TGAGs, collagen and TSA, with marked increase in FGA liver tissue content. The elevated FGA with depressed TSA content of liver tissue may be attributed to a cancer-hampered N-acetylation of FGA into SA. 5-FU administration markedly depressed hepatic tissue proteolysis, possibly reactivated N-acetylation of FGA into SA and elevated TGAGs without stopping tissue fibrosis as collagen was not affected. This study explores additional pathways for the mechanism of action of 5-FU, through conservation of extracellular matrix composition in situ, inhibiting invasion and metastasis in addition to its DNA-disturbing pathway.
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PMID:Novel biochemical pathways for 5-Fluorouracil in managing experimental hepatocellular carcinoma in rats. 2017 69


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