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)

Thirty-two children with solid tumors (lymphangioma, fibrosarcoma, hepatocarcinoma, osteogenic sarcoma, rhabdomyosarcoma, lymphosarcoma, mesenchymoma, hepatoma, Ewing's sarcoma, reticulum cell sarcoma, neuroblastoma, Hodgkin's disease, and brain tumors) were studied for alterations in coagulation by means of platelet counts, platelet aggregation, thrombelastogram, procoagulant and antigenic factor VIII, fibrin split products, and antithrombin III level. Results indicated hypercoagulability as shown by abnormally short thrombelastograms and elevated factor VIII levels and platelet counts in approximately one-half of the group. With the exception of increased fibrin split products in a third of the patients, little laboratory or clinical evidence for disseminated intravascular coagulation was seen. Hypercoagulability, as noted in adult carcinoma patients, can also occur in childhood sarcoma patients.
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PMID:Hypercoagulability in childhood cancer. 120 73

Liver biopsy specimens with or without liver diseases were examined immunohistochemically to determine the distribution of endothelial cell markers, factor VIII-related antigen (FVIII-RAg). Ulex europaeus agglutinin I (UEA-I) lectin and PAL-E. We also investigated the localization of laminin, a component of the basement membrane. In normal livers, FVIII-RAg, UEA-I and laminin were negative in sinusoidal endothelial cells, but positive in blood vascular endothelia of the portal area. The antigen detected by PAL-E was distributed in venous endothelial cells. PAL-E did not label endothelial cells of the artery. In the lobule, immunoreactivity with PAL-E was weakly detected only in some sinusoids of the periportal area. In chronic active hepatitis and liver cirrhosis, FVIII-RAg and UEA-I stained endothelial cells of neovasculatures in the enlarged portal areas of the fibrous septum surrounding pseudolobules. Some sinusoidal endothelial cells in cirrhotic livers were reactive to UEA-I and FVIII-RAg, whereas PAL-E-positive cells were found rarely in the pseudolobules. In carcinomatous sinusoidal endothelial cells, FVIII-RAg, UEA-I and PAL-E were strongly stained. Laminin underlay these carcinomatous sinusoids. These suggest capillarization of sinusoids in hepatocellular carcinoma. The histochemical approach using endothelial cell markers could be a practical tool in the diagnosis of hepatocellular carcinoma.
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PMID:Histochemical properties of vascular and sinusoidal endothelial cells in liver diseases. 165 46

Adenomatous hyperplasia, a hyperplastic parenchymal nodule in the cirrhotic liver, has been presumed to be a preneoplastic lesion in human hepatocarcinogenesis. In this study, phenotypes of the sinusoidal endothelium were examined in adenomatous hyperplasia, hepatocellular carcinoma, cirrhosis, chronic active hepatitis, and normal livers. Adenomatous hyperplasia (n = 74) was histologically classified into two types: ordinary (n = 35) and atypical (n = 39). While the former lacked hepatocellular atypia, the latter consisted of atypical hepatocytes equivocal as to benignity and malignancy, in some of which overt malignant foci were found. The expression of A, B, and H blood group antigens, receptors of Ulex europaeus agglutinin I, and factor VIII-related antigen on the sinusoidal endothelium was minimal or nil in normal livers. It was mild and focal in chronic active hepatitis, cirrhosis, and ordinary adenomatous hyperplasia, while expression was moderate in atypical adenomatous hyperplasia with or without malignant foci, and severe in malignant foci in atypical adenomatous hyperplasia and in hepatocellular carcinoma. These data suggest that phenotypes of the sinusoidal endothelium of atypical adenomatous hyperplasia are closely related to the development of hepatocellular carcinoma, and phenotypic changes of the sinusoidal endothelium occur stepwise corresponding to various stages of hepatocarcinogenesis in cirrhotic livers.
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PMID:Expression of ABH blood group antigens, receptors of Ulex europaeus agglutinin I, and factor VIII-related antigen on sinusoidal endothelial cells in adenomatous hyperplasia in human cirrhotic livers. 185 20

The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied in North East England in blood donors, local multiply transfused patients, local high risk individuals, and chronic liver disease patients. Anti-HCV was detected by enzyme-linked immunosorbent assay (ELISA) in 2/1120 (0.18%) blood donors; 1/84 chronic renal failure patients on haemodialysis who had received 1,992 units of blood (seroconversion rate of 0.05% per unit transfused), 1/207 cardiac patients 6 months post cardiac surgery transfused with 1,403 units of blood (1 anti-HCV pre-operatively, seroconversion rate 0.07%), 40/50 haemophilia A patients treated with commercial factor VIII, and 38/100 intravenous drug users. In addition anti-HCV was detected by ELISA in 5/35 cryptogenic chronic liver disease patients, 5/5 confirmed by recombinant immunoblot assay (RIBA) (14%); 3/30 patients with autoimmune chronic active hepatitis, 2/3 by RIBA (7%); 2/50 primary biliary cirrhosis patients, 1/2 by RIBA (2%); 0/30 alcoholic cirrhosis patients; and 2/9 patients with hepatocellular carcinoma, 1/2 by RIBA (11%). HCV is uncommon in North East England; it may be implicated in the aetiology of a minority of cases of cryptogenic liver disease and less than 5% of autoimmune chronic active hepatitis and primary biliary cirrhosis.
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PMID:Low prevalence of antibody to hepatitis C virus in north east England. 196 76

Vessels around the intrahepatic large bile ducts (peribiliary vascular plexus) were examined by histologic, immunohistochemical and scanning electron microscopic observations. The vessels within duct walls were mainly capillaries, while those around the duct walls were composed of capillaries and venules. A majority of vessels was positive for factor VIII-related antigen and Ulex europaeus lectin I. Scanning electron microscopy of hepatic arterial and biliary casts revealed that bile ducts were surrounded by the vascular plexus derived from hepatic arterial branches, and serial section observations in addition disclosed the vessels connecting the peribiliary plexus with portal venous branches ('internal roots'). The peribiliary vascular plexus was increased considerably in livers with portal hypertension, especially idiopathic portal hypertension, extrahepatic portal venous obstruction and hepatocellular carcinoma with portal venous tumor thrombi. Internal roots were also frequently found in the livers with portal hypertension. These results suggest that altered intrahepatic hemodynamics in portal hypertensive conditions involves the peribiliary vascular plexus, resulting in an increase of the number and frequent occurrence of 'internal roots', these vessels probably operating as intrahepatic collaterals.
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PMID:Vascular plexus around intrahepatic bile ducts in normal livers and portal hypertension. 254 Nov 96

A murine cultured cell line (MKM-O) was established from a tumor of a BALB/C (nu/nu) mouse that had been subcutaneously inoculated with human hepatoma tissue fragments in the same location. The MKM-O cell line was proven to be of endothelial origin by morphological examinations and positive staining with fluorescein-labeled antibody against factor VIII antigen. MKM-O cells grown in vitro produced a colony-stimulating factor (CSF) and a leukemia cell-growth factor (LC-GF). CSF from MKM-O acted on both human and murine bone marrow-derived granulocytes and macrophage colony-forming units (CFU-GM). The activity of LC-GF on human leukemia cell lines (HL-60, HSB-2, CEM, DAUDI and K562) was demonstrated both in conditioned medium (CM) of MKM-O and of rat vascular endothelial cells. The CM of MKM-O also demonstrated a limited growth promoting activity against the mononuclear cells from human cord blood and improved their survival, suggesting that endothelial cells play an important role in the proliferation and differentiation of blood cells.
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PMID:Colony-stimulating factor and leukemia cell-growth factor produced by a murine endothelial cell line, MKM-O. 282 70

Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI-3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI-3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK-HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.
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PMID:Constitutive production of leukemia differentiation, colony-stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor. 299 Jun 10

Although several investigators have attempted to identify the site of synthesis of factor VIII (FVIII), the cellular species responsible for maintenance of plasma FVIII has not been clearly defined. Indications point at hepatocytes and certain endothelial cells. The present study investigated the FVIII coagulant antigen (VIII:Ag) of hepatocytes obtained by two-step collagenase digests of human liver pieces. Following Percoll gradient centrifugation, less than 1% of cells harvested were non-parenchymal. Lysates of freshly isolated and purified hepatocytes contained 165-250 mU of VIII:Ag/10(6) cells as defined by a two-site ELISA employing a haemophilic antibody against human FVIII. This material contained a single peak of VIII:Ag polypeptides as judged from the VIII:Ag ELISA profile of Mono-Q fast protein liquid chromatography fractions. A haemophilic antibody specific for epitopes of the light chain of FVIII, employed in immunoisolation of VIII:Ag in lysate of human hepatocytes, extracted a polypeptide pattern that was studied in a reduced SDS-PAGE electrophoresis gel and compared to that of immunoisolate from normal plasma. After electroblotting onto nitrocellulose and reaction with a monoclonal antibody towards the light chain of FVIII, the appearance of a doublet at 78-79 kDa in both these materials indicated the presence of the light chain of FVIII in human hepatocyte lysate. During culture, human hepatocytes secreted 20-80 mU of VIII:Ag per 1 x 10(6) cells per 24 hours. Further, a significant secretion of VIII:Ag was found in media of cultured human hepatoma cells, Hep-G2, whereas human blood monocytes and human fibroblasts did not secrete detectable VIII:Ag. In all of these cell cultures, vWf:Ag was indetectable or present as trace.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis of factor VIII in human hepatocytes in culture. 314 45

The morphological and phenotypic changes of sinusoidal endothelial cells in hepatocellular carcinoma were investigated along with the hemodynamic changes. Hepatocellular carcinomas, which were 10-20 mm in diameter, were obtained by liver aspiration biopsy. Twenty specimens of well differentiated and 20 specimens of moderately differentiated hepatocellular carcinoma were used. These were classified into two groups of hepatocellular carcinoma: with and without hypervascularity. Electron microscopy, immunohistochemistry using antibodies against factor VIII-related antigen, type IV collagen and laminin and lectin histochemistry using Ulex europaeus agglutinin I (UEA-I) were performed. Factor VIII-related antigen and UEA-1 binding sites were present in the sinusoidal endothelial cells in two groups. In hepatocellular carcinoma with hypervascularity, type IV collagen and laminin were present corresponding to basement membranes along the endothelial cells, which had few fenestrae. In another group, although type IV collagen was present along the endothelial cells that had a few fenestrae, laminin and basement membranes were rarely observed. These results suggest that the sinusoidal endothelial cells tend to show phenotypic changes in the early stage of hepatocarcinogenesis. As the arterial blood supply for hepatocellular carcinoma increases, the sinusoidal endothelial cells may form basement membranes and take on the morphological appearance of capillaries.
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PMID:Sinusoidal capillarization in small hepatocellular carcinoma. 753 May 63

Hemophilia A is caused by blood coagulation factor VIII (FVIII) deficiency and is an attractive target for gene therapy. However, features of FVIII physiology, such as the instability of the mRNA and protein, have provided obstacles to the design of a feasible strategy for the transfer and expression of the human FVIII gene in vivo. We have constructed a recombinant adenoviral vector, Av1ALH81, that contains the human FVIII cDNA from which the B-domain has been deleted (BDD FVIII) and extensively characterized this vector in vitro and in vivo. In vitro, HepG2, human hepatoma cells, transduced with Av1ALH81 secreted high levels of biologically active human BDD FVIII measured by the Coatest bioassay (> 2,400 mU per 10(6) cells per 24 hr). Administration of Av1ALH81 to mice, via tail vein, resulted in expression of human BDD FVIII in the mouse plasma at levels averaging 307 +/- 93 ng/ml 1 week post-injection, measured by a sensitive human FVIII-specific ELISA. Normal FVIII levels in humans are 100-200 ng/ml, and therapeutic levels are as low as 10 ng/ml. Purification of the human FVIII from the mouse plasma, and subsequent Coatest analysis, revealed that the human FVIII produced in the mice was biologically active. In addition, the duration of FVIII expression in vivo was followed, and high-level FVIII expression was sustained over a period of several weeks. The finding that an adenoviral vector can mediate high-level expression of human FVIII in an animal model provides the basis for the development of gene therapy for hemophilia A.
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PMID:In vivo gene delivery and expression of physiological levels of functional human factor VIII in mice. 753 39


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