muramidase and Liver-Neoplasms

A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amylases; Aryl Hydrocarbon Hydroxylases; Bone Neoplasms; Clinical Enzyme Tests; gamma-Glutamyltransferase; Humans; Isoenzymes; Isomerases; Leucyl Aminopeptidase; Lipase; Liver Neoplasms; Lung Neoplasms; Male; Muramidase; Neoplasms; Nucleotidases; Oxidoreductases; Pancreatic Neoplasms; Prostatic Neoplasms; Sulfatases

Topics: Alcoholism; Aminopeptidases; Amylases; Aspartate Aminotransferases; Cholinesterases; Creatine Kinase; Cystic Fibrosis; Enzyme Activation; Enzymes; Female; gamma-Glutamyltransferase; Half-Life; Humans; Isoenzymes; L-Lactate Dehydrogenase; Liver Cirrhosis; Liver Neoplasms; Muramidase; Myocardial Infarction; Pepsinogens; Phenobarbital; Porphyrias; Pregnancy

Topics: Acid Phosphatase; Alkaline Phosphatase; Fructose-Bisphosphate Aldolase; Glucose-6-Phosphate Isomerase; Humans; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Leukemia; Liver Neoplasms; Mass Screening; Muramidase; Neoplasm Metastasis; Neoplasms; Nucleotidases; Phosphoglucomutase

Hepatocellular carcinoma (HCC) takes the predominant malignancy of hepatocytes with bleak outcomes owing to high heterogeneity among patients. Personalized treatments based on molecular profiles will better improve patients' prognosis. Lysozyme (LYZ), a secretory protein with antibacterial function generally expressed in monocytes/macrophages, has been observed for the prognostic implications in different types of tumors. However, studies about the explicit applicative scenarios and mechanisms for tumor progression are still quite limited, especially for HCC. Here, based on the proteomic molecular classification data of early-stage HCC, we revealed that the LYZ level was elevated significantly in the most malignant HCC subtype and could serve as an independent prognostic predictor for HCC patients. Molecular profiles of LYZ-high HCCs were typical of those for the most malignant HCC subtype, with impaired metabolism, along with promoted proliferation and metastasis characteristics. Further studies demonstrated that LYZ tended to be aberrantly expressed in poorly differentiated HCC cells, which was regulated by STAT3 activation. LYZ promoted HCC proliferation and migration in both autocrine and paracrine manners independent of the muramidase activity through the activation of downstream protumoral signaling pathways via cell surface GRP78. Subcutaneous and orthotopic xenograft tumor models indicated that targeting LYZ inhibited HCC growth markedly in NOD/SCID mice. These results propose LYZ as a prognostic biomarker and therapeutic target for the subclass of HCC with an aggressive phenotype.

Topics: Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Mice; Mice, Inbred NOD; Mice, SCID; Muramidase; Neoplastic Processes; Prognosis; Proteomics

ABIN1, an important immune regulator, has been shown to be involved in various cellular functions, such as immunity, development, tissue homeostasis, and tumor progression. It inhibits TNF- and TLR-induced NF-κB signaling activation and the consequent gene expression. Despite its functional significance, the mechanism of ABIN1 in the regulation of various cellular functions remains unclear. In this study, we identified HDAC1, a key regulator of eukaryotic gene expression and many important cellular events, including cell proliferation, differentiation, cancer and immunity, as an interacting partner of ABIN1. The results showed that ABIN1 acted as a modulator to down-regulate HDAC1 ubiquitination via three different linkages, thereby stabilizing HDAC1 by inhibiting its lysosomal and proteasomal degradation. Interestingly, the inhibitory function of ABIN1 required direct binding with HDAC1. Moreover, the level of p53, which was a tumor suppressor and a well-studied substrate of HDAC1, was under the regulation of ABIN1 via the modulation of HDAC1 levels, suggesting that ABIN1 was physiologically significant in tumor progression. This study has revealed a new function of ABIN1 in mediating HDAC1 modification and stability.

Topics: A549 Cells; Carcinoma, Hepatocellular; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Gene Knockout Techniques; HeLa Cells; Hep G2 Cells; Histone Deacetylase 1; Humans; K562 Cells; Liver Neoplasms; Lung Neoplasms; Muramidase; Neoplasms; Proteasome Endopeptidase Complex; Protein Stability; Tumor Suppressor Protein p53; Ubiquitination

The influences of caffeine, lysozyme and the joint application of them on the hepatoma cell line HepG2 proliferation inhibition and cell apoptosis were observed by 3-(4, 5-dimethyl-2-thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and Hoechst 33342, which showed the proliferation inhibition rate of the joint application on HepG2 cells was 47.21%, significantly higher than caffeine or lysozyme, and the joint application promoted the apoptosis of HepG2 cells obviously. Van't Hoff classical thermodynamics formula, the Föster theory of non-radiation energy transfer and fluorescence phase diagram were used to manifest that the process of lysozyme binding to caffeine followed a two-state model, which was spontaneous at low temperature driven by enthalpy change, and the predominant intermolecular force was hydrogen bonding or Van der Waals force to stabilize caffeine-lysozyme complex with the distance 5.86nm. The attenuated total reflection-Fourier transform infrared spectra indicated that caffeine decreased the relative contents of α-helix and β-turn, which inferred the structure of lysozyme tended to be "loose". Synchronous fluorescence spectra and ultraviolet spectra supported the above conclusion. The amino acid residues in the cleft of lysozyme were exposed and electropositivity was increased attributing to the loose structure, which were conducive to increasing caffeine concentration on the HepG2 cell surface by electrostatic interaction to show synergistic effect.

Topics: Apoptosis; Caffeine; Carcinoma, Hepatocellular; Cell Proliferation; Drug Synergism; Hep G2 Cells; Humans; Liver Neoplasms; Muramidase

Histiocytic sarcoma is the most frequent hematopoietic tumor in rats. We report here a histiocytic sarcoma infiltrating the liver, the spleen and the pancreas from a Wistar rat. In the liver, the tumor was associated with oval cell and bile duct hyperplasia. The cells looked like neoplastic histocytic cells described in this species but with some particularities (e.g. lack of multinucleated giant cells). At immunohistochemistry, neoplastic cells in the liver were vimentine positive but lysozyme and CD68 negative. In the kidney, lysozyme-positive cytoplasmic droplets were observed. We describe here an atypical case of histiocytic sarcoma in the rat and we compare the nature of these neoplastic cells to other species.

Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Histiocytic Sarcoma; Immunohistochemistry; Kidney; Liver Neoplasms; Male; Muramidase; Pancreatic Neoplasms; Rats; Rats, Wistar; Splenic Neoplasms; Vimentin

Immunohistochemical and ultrastructural studies were performed on the sinusoidal lining cells of eight canine hepatocellular carcinomas. The sinusoidal endothelial cells of the tumors had a positive reaction for both Factor VIII-related antigen and peanut agglutinin, but did not bind with Ulex europaeus agglutinin-1. Desmin- and lysozyme-positive cells were present along the sinusoids and perisnusoidal spaces of the tumor tissues, respectively, but were fewer in number compared with those of normal canine liver. Alpha-Smooth muscle actin-positive cells outlining the sinusoids were frequently observed. Electron microscopy revealed that basement membranes were often formed beneath the sinusoidal endothelial cells, with rare fenestration. Macrophages were present around or within the sinusoids and tended to increase in number relative to the degree of tumor differentiation. Myofibroblast-like cells with various morphological features, consistent with alpha-smooth muscle actin-positive cells, were frequently found in the perisinusoidal space. The present study indicates that the sinusoidal lining cells of canine hepatocellular carcinoma have some phenotypic characteristics.

Topics: Actins; Animals; Carcinoma, Hepatocellular; Desmin; Dog Diseases; Dogs; Female; Immunohistochemistry; Lectins; Liver Neoplasms; Macrophages; Male; Microscopy, Electron; Muramidase; Peanut Agglutinin; von Willebrand Factor

Topics: Asialoglycoproteins; Hepatoblastoma; HN Protein; Humans; Liver; Liver Neoplasms; Macromolecular Substances; Membrane Fusion; Microinjections; Muramidase; Parainfluenza Virus 1, Human; Receptors, Cell Surface; Tumor Cells, Cultured; Viral Fusion Proteins

Plasma lysozyme levels are elevated in several different pathological conditions. In our study we show that well differentiated human hepatoma cells Hep3B and HepG2 are active synthesis sites of lysozyme and that this synthesis can be modulated by acute phase mediators. The production and modulation of lysozyme synthesis was studied by means of Northern-blot analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a specific bioassay after treatment of the cells with interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha. Hep3B and HepG2 cells constitutively synthesize high amounts of lysozyme. Lysozyme synthesis and secretion were found to be augmented by interleukin-1 beta and tumor necrosis factor-alpha in both cell lines. Interleukin-6 caused an increase in lysozyme production in Hep3B but a decrease in the HepG2 cells. As expected, the synthesis of albumin was decreased in both cell lines. Furthermore we demonstrated that HepG2 and Hep3B cells produce a biologically active form of the enzyme as measured by a specific bioassay. The results demonstrate that lysozyme is constitutively synthesized by Hep3B and HepG2 hepatoma cell lines and that lysozyme synthesis is modulated by acute-phase mediators. Well differentiated human hepatoma cells may respond differently to different cytokines.

Topics: Albumins; Blotting, Northern; Carcinoma, Hepatocellular; Cytokines; Gene Expression Regulation, Enzymologic; Humans; Interleukin-1; Interleukin-6; Liver Neoplasms; Muramidase; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

The potential of reconstituted Sendai viral envelopes containing only the fusion protein (F-virosomes) was evaluated for a targeted cytosolic delivery of lysozyme to human hepatoblastoma cells (HepG2) in culture. 125I-Lysozyme loaded into F-virosomes was used to monitor its fusion-mediated transfer to the HepG2 cells. Using fusion assay based on the transfer of water soluble probe, we have demonstrated the existence of aqueous connection between F-virosomes and target cells. Target specificity of the F-virosomes was ensured by the strong interaction between terminal beta-galactose moiety of F protein and the asialoglycoprotein receptor on the membrane of HepG2 cells. Incubation of the loaded F-virosomes with cells resulted in fusion-mediated injection, as inferred from the ability of cells to internalize lysozyme in the presence of azide (an inhibitor of the endocytotic process). Binding as well as fusion of the F-virosomes to HepG2 cells was solely mediated by the F protein. Introduction of 125I-lysozyme into the HepG2 cells was confirmed by selective accumulation of acid and antibody-precipitable radioactivity in the cytosolic compartment. The structural integrity of the internalized lysozyme was also assessed. The potential usefulness of F-virosomes with defined specificities as biological carrier for both in vitro and in vivo cytosolic delivery of macromolecules and drugs has been established.

Topics: Asialoglycoprotein Receptor; Asialoglycoproteins; Biological Transport; Cell Line; Galactose; Hepatoblastoma; Humans; Kinetics; Liver Neoplasms; Membrane Fusion; Microinjections; Muramidase; Neuraminidase; Parainfluenza Virus 1, Human; Receptors, Cell Surface; Subcellular Fractions; Tumor Cells, Cultured; Viral Fusion Proteins

Pathologic features of eight cases of undifferentiated (embryonal) sarcoma of the liver (USL) in childhood were studied. Light microscopic examination showed a diffuse growth of spindle cells with occasional polygonal cells and multinucleated giant cells and also revealed focal areas of storiform pattern in four tumors, cambium layer formation in one tumor, and alveolar arrangement in one tumor. Immunohistochemical study showed positive staining of proliferating cells for suggestive histiocytic markers (A1AT in 6/6, A1ACT in 5/6, lysozyme in 4/6, and KP1 in 4/6) and for muscle markers (desmin in 4/6 and HHF35 in 3/6). Ultrastructural examination demonstrated that the individual tumors were composed of a mixture of cells having fibroblastic, histiocytoid, fibrohistiocytoid, myofibroblastic, and undifferentiated (primitive mesenchymal) morphologies. Also identified were cells with definite myoblastic morphology in three tumors: leiomyoblastic in one and rhabdomyoblastic in two. In conclusion, the tumor cells in USL show phenotypical diversity comparable to those of malignant fibrous histiocytoma with or without additional rhabdomyosarcomatous or leiomyosarcomatous differentiation.

Topics: Actins; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; alpha-Fetoproteins; Cell Transformation, Neoplastic; Desmin; Female; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Membrane Glycoproteins; Mesenchymoma; Microscopy, Electron; Mucin-1; Muramidase; S100 Proteins; Vimentin

Hematoxylin and eosin (H-E) stained liver sections of 47 autopsy cases of hepatic malignancies were examined. There were 43 cases of hepatocellular carcinoma (subtypes of 30 trabecular, 7 solid, 5 pseudoglandular, and one scirrhous carcinoma), 3 of cholangiocellular carcinoma and one of mixed carcinoma. After immunohistochemical staining, benign hepatocytes reacted positively with anti-epithelial membrane antigen (EMA). Hepatocellular carcinoma cells reacted more weakly than benign hepatocytes. It was noted that the microtubular structure, which could not be demonstrated even by alcian blue or cationic ferric hydroxide colloid stabilized with cacodylate (Fe-CaC), was clearly detected with anti-EMA. The EMA-positive microtubular structures may indicate terminal cholangiolar differentiation. Based on EMA, seven more cases formerly classified as hepatocellular carcinoma by H-E were reclassified as mixed carcinoma, totaling eight (17.0%). The histologic classification of "mixed carcinoma" has been 1.5 to 2.0% of primary liver cancers in Japan, but we suggest there may be more cases of "mixed carcinoma" identified in the future. In conclusion, we emphasize that EMA staining is useful for more accurate classification of hepatic tumors.

Topics: Adenoma, Bile Duct; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins; Carcinoma, Hepatocellular; Female; Humans; Immunohistochemistry; Liver Neoplasms; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Muramidase

The sinusoids of 30 human hepatocellular carcinomas of various types were examined by electron microscopy and histochemically for binding to the Ulex europaeus lectin (UEA1). A population of sinusoidal macrophages was identified with an antibody to lysozyme (muramidase). The UEA1 binding was negative in normal sinusoids but positive in the tumor vessels. Macrophages resembling Kupffer cells were found within the tumor vessels but in smaller numbers than in either normal or cirrhotic liver tissue. Fibrolamellar and sclerosing carcinomas contained the smallest numbers. Ultrastructurally, endothelial cells of tumor vessels were thicker than normal, with fewer fenestrations. They contained bundles of microfilaments and showed basement membrane formation. Subendothelial myoid cells were found. These findings indicate that the sinusoidal vessels of hepatocellular carcinomas show features of true capillaries and precapillary blood vessels. The degree of this difference from normal hepatic sinusoids may reflect the relative immaturity of the cancer cells.

Topics: Adolescent; Adult; Aged; Carcinoma, Hepatocellular; Female; Humans; Immunoenzyme Techniques; Lectins; Liver Neoplasms; Macrophages; Male; Middle Aged; Muramidase; Plant Lectins; Staining and Labeling

We have immunohistochemically localized fibronectin, lysozyme and alpha-fetoprotein (AFP) in 21 human hepatocellular carcinoma (HCC) tissues obtained by surgical resection at both light and electron microscopic levels. Three distinct distribution patterns of fibronectin (sinusoidal, periacinar, and pericellular patterns) were observed. The sinusoidal and periacinar patterns were mainly observed in HCC of pseudoglandular or trabecular patterns and of Edmondson's grade I or II, whereas the pericellular pattern was observed in HCC of compact or trabecular patterns and of Edmondson's III grade, suggesting that the pericellular fibronectin was rather associated with undifferentiated HCC. Electron microscopic observation of the pericellular fibronectin showed fibronectin to be present in the dilated intercellular spaces where microvilli were moderately developed. We observed intracytoplasmic staining of fibronectin in 2 of the 21 HCC cases. By immunoelectron microscopy, fibronectin was observed in the endoplasmic reticulum (ER) of some HCC cells. In the 21 HCC cases, lysozyme-positive cancer cells were observed in 10 cases, and AFP in 6 cases. At the ultrastructural level, lysozyme was identified in the ER and the perinuclear spaces of HCC cells, suggesting that lysozyme was synthesized by these cells. Lysozyme-positive cases tended to be more frequently observed in cases with the pericellular pattern of fibronectin rather than those with sinusoidal or periacinar patterns.

Topics: Adult; Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Endoplasmic Reticulum; Female; Fibronectins; Humans; Immunoenzyme Techniques; Liver Neoplasms; Male; Middle Aged; Muramidase

Hepatocellular adenomas are usually visualized as defects on technetium-99m-sulfur colloid liver scans, a fact which has been attributed to the absence of phagocytic Kupffer cells in the tumors. To determine whether this is true, seven hepatocellular adenomas were subjected to immunoperoxidase staining for lysozyme, a marker of mononuclear phagocytes. The Kupffer cells were counted in the tumors and surrounding non-neoplastic liver. All hepatocellular adenomas studied were found to contain Kupffer cells. Three tumors had fewer Kupffer cells than the surrounding liver. Three had about the same number as the surrounding liver, and one had more Kupffer cells than the non-neoplastic liver. Thus, the lack of phagocytosis of colloid in liver scans is probably due to something other than a deficiency of Kupffer cells in the hepatocellular adenomas.

Topics: Adult; Carcinoma, Hepatocellular; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Kupffer Cells; Liver Neoplasms; Muramidase; Radionuclide Imaging

Five cases of inflammatory pseudotumour of the liver are reported and compared with seven individual previously published case reports. Clinical presentation was variable but often comprised low grade intermittent fever, vague abdominal symptoms, and a history of weight loss. Leucocytosis, raised erythrocyte sedimentation rate, and polyclonal hyperglobulinaemia were also sometimes detected. All five cases in the present series were considered to be clinically malignant; and in two the histological diagnosis was also that of malignancy. The lesion is clearly inflammatory and reactive, but the aetiology remains unknown.

Topics: alpha 1-Antitrypsin; Antigens; Blood Sedimentation; Child; Child, Preschool; Factor VIII; Female; Fibroma; Humans; Immunoglobulins; Leukocyte Count; Liver Neoplasms; Male; Middle Aged; Muramidase; von Willebrand Factor

A 71-year-old male presenting high fever, pancytopenia, liver dysfunction and jaundice died without a confirmed diagnosis. Microscopically, histiocytes with marked atypia and erythrophagocytosis had infiltrated the spleen, enlarged lymph nodes, liver, and bone marrow. From the above features this case was diagnosed as malignant histiocytosis. The infiltrating histiocytes were classified into three categories: 1) phagocytic cells, 2) atypical, mostly non-phagocytic cells, and 3) bizarre cells including multinucleated giant cells. An immunohistochemical study of histiocyte markers demonstrated that lysozyme was positive in the atypical cells and some phagocytic cells, whereas alpha-l-antitrypsin tended to be localized in the phagocytic cells. Bizarre cells were negative for both markers. No S-100 protein was demonstrated in the neoplastic cells. These immunohistochemical features suggested monocyte-phagocytic origin of the tumor in this case.

Topics: Aged; alpha 1-Antitrypsin; Bone Marrow; Histiocytes; Humans; Immunoglobulins; Liver Neoplasms; Lymph Nodes; Lymphatic Diseases; Male; Muramidase; Phagocytes; S100 Proteins; Splenic Neoplasms

Topics: Animals; Carcinoma, Hepatocellular; Cell Adhesion; Cells, Cultured; Cytotoxicity, Immunologic; Fibrosarcoma; Guinea Pigs; Liver Neoplasms; Liver Neoplasms, Experimental; Macrophages; Muramidase; Mycobacterium bovis; Phytohemagglutinins; Solubility; Tuberculin

Topics: Acid Phosphatase; Clinical Enzyme Tests; Humans; L-Lactate Dehydrogenase; Leukemia; Liver Neoplasms; Muramidase; Neoplasms

The study of some factors of nonspecific immunity in 85 patients with cirrhosis and in 9 patients with primary cancer of the liver revealed a decrease of all factors of nonspecific immunity under consideration, while in primary cancer of the liver--selective and more sharp fall of properdin level. The complement, as compared with the control, was not changed, whereas lysozyme was statistically reliably higher than in healthy persons.

Topics: Adult; Aged; Complement System Proteins; Diagnosis, Differential; Humans; Immunity; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Muramidase; Properdin

The serum muramidase levels were measured in 128 patients with primary or metastatic colorectal cancer, 166 tumour-free patients after resection of a colorectal cancer, and 172 controls. Muramidase levels over 10 mug/ml were detected in 30%-39% of the tumour-bearing patients, in 8.2% of the tumour free, and in only 1.7% of the controls (normal level 6.68 +/- 1.42 mug/ml). Long-term follow up indicated that raised levels may occur as a transient phenomenon in recurrent or metastatic disease. The likely relation of abnormal serum muramidase activity and stimulation of the reticuloendothelial system is discussed.

Topics: Adenocarcinoma; Carcinoembryonic Antigen; Colonic Neoplasms; Creatinine; gamma-Glutamyltransferase; Humans; Kidney Failure, Chronic; Leucyl Aminopeptidase; Liver Neoplasms; Muramidase; Neoplasm Metastasis; Rectal Neoplasms; Recurrence

Topics: Animals; Antigens, Neoplasm; Carcinoma, Hepatocellular; Cell Membrane; Chromatography, DEAE-Cellulose; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Galactosidases; Glucosidases; Hyaluronoglucosaminidase; Liver Neoplasms; Muramidase; Neoplasm Proteins; Neoplasms, Experimental; Neuraminidase; Organ Size; p-Dimethylaminoazobenzene; Papain; Peptide Hydrolases; Rats; Solubility; Time Factors; Trypsin