Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histochemical, immunohistochemical and ultrastructural studies were performed on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was observed in 3 (5.5%) of 55 consecutively resected HCC cases. Histologically, a large number of hepatocytes displayed pale or eosinophilic staining of the cytoplasm, resulting in ground-glass appearance. They were aggregated in nodular pattern, or diffusely intermixed with other malignant hepatocytes. PBs were negative for periodic-acid Schiff and Masson's trichrome staining. The inclusions showed a strong positive reaction for fibrinogen and some of them were weakly positive for albumin but negative for hepatitis B surface antigen, hepatitis B core antigen, alpha-fetoprotein and alpha-1-antitrypsin. Ultrastructurally, PBs were membrane-bound and contained granular materials of moderate electron density, and were closely related to dilated rough endoplasmic reticulum. These findings support that PBs are secretory fibrinogen accumulated in cystic ER and that such intracellular accumulation possibly reflects a defective transport of fibrinogen.
 ...
PMID:Pale bodies in hepatocellular carcinoma. 1106 87

This study was designed to investigate the alterations of individual protein kinase C (PKC) isoforms in human liver cancer. Surgical specimens of hepatocellular carcinoma and adjacent normal tissues were extracted into cytosolic and membranous fractions. The level of membrane-bound PKCalpha in the cancer tissue was significantly lower than that in the adjacent normal tissue and consistent with the change in PKC activity. In addition, there was a significant negative correlation between PKCalpha and tumor size. In both cytosolic and membrane fractions, levels of PKCdelta and PKCzeta was significantly higher in the cancer tissue than those in the adjacent normal liver tissue. The alterations in the PKC isoforms signify their roles in the hyperproliferation in liver cancer.
 ...
PMID:Alteration in the expression of protein kinase C isoforms in human hepatocellular carcinoma. 1109 Sep 66

It is currently unclear whether the hepatocellular damage in chronic hepatitis C virus (HCV) infection is produced through the intrahepatic action of the anti-HCV immune response or through a direct cytopathic effect. In order to investigate the features of HCV replication (morphogenesis and cytopathic effect), we studied the infection of a permissive lymphocytic B cell line, Daudi cells, which were infected with sera of HCV-positive patients, and were examined after various time points under electron microscope. Viral genomic RNA was detected by in situ hybridization, and apoptosis with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The amount of viral genomic RNA was observed to increase during infection. HCV replicated rapidly, since characteristics of viral morphogenesis resembling those of yellow fever virus in a hepatoma cell line could be found 2 days after infection. These included the following: a) several viral particles identical in size (about 42 nm) and structure (a spherical 30-nm-sized electron-dense nucleocapsid surrounded by a membrane) to yellow fever virus were present in the cytoplasm of cells displaying already typical signs of the early stage of apoptosis; b) numerous membrane-bound organelles and in particular the endoplasmic reticulum and vacuoles were observed; c) proliferation of membranes was apparent; and d) intracytoplasmic electron-dense inclusion bodies which have been demonstrated to correspond to nucleocapsids for other flaviviruses were detected. Several cells presented electron-dense areas in the endoplasmic reticulum displaying 30-nm circular structures lying among an amorphous material. Striking cytopathic features with ballooning, extremely enlarged vacuoles and signs of apoptosis were found in cells often containing sequestered aggregates of virus-like particles. By in situ hybridization we found that such enlarged cells contained HCV RNA. Our results thus indicate that the ultrastructural features of HCV viral particles and their morphogenesis resemble that of yellow fever virus and dengue virus. In Daudi cells, HCV infection seems to rapidly trigger apoptotic cell death, and efficient release of viral particles does not seem to take place.
 ...
PMID:Ultrastructural observations in hepatitis C virus-infected lymphoid cells. 1135 13

A novel anti-human DR5 monoclonal antibody, TRA-8, induces apoptosis of most tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-sensitive tumor cells both in vitro and in vivo. In contrast to both the membrane-bound form of human TRAIL, which induced severe hepatitis in mice, and the soluble form of human TRAIL, which induced apoptosis of normal human hepatocytes in vitro, TRA-8 did not induce significant cell death of normal human hepatocytes. However, both primary hepatocellular carcinoma cells and an established liver cancer cell line were highly susceptible to the killing mediated by TRA-8. We show here that elevated levels of cell-surface expression of DR5 and increased susceptibility to DR5-mediated apoptosis are characteristics of malignant tumor cells. In contrast, DR5 alone is not sufficient to trigger apoptosis of normal hepatocytes. Therefore, selective, specific targeting of DR5 with an agonistic antibody might be a safe and effective strategy for cancer therapy.
 ...
PMID:Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. 1147 29

Fibrolamellar carcinoma of the liver is a distinctive variant of hepatocellular carcinoma characterized histologically by trabeculae of oncocytic cells with intervening lamellae of collagen fibers. We describe a case with a prominent component of clear cells, a feature not previously recognized in this tumor type. The patient was a 59-year-old woman incidentally found to have a solitary liver tumor, measuring 5 cm. Pathologic examination revealed a circumscribed, firm, tan tumor with peculiar concentric streaks. Oncocytic cells and clear cells were arranged in trabeculae separated by lamellae of collagen or sinusoids. The clear cells possessed abundant finely reticulated clear cytoplasm, which was highlighted by trichrome stain and immunostaining with antimitochondria antibody. Ultrastructurally, the cytoplasm of the clear cells was packed with empty membrane-bound vesicles that occasionally contained short cristae. The features suggested that the clear cell change resulted from ballooning and rarefactive changes of mitochondria. Clear cell fibrolamellar carcinoma should not be confused with conventional clear cell hepatocellular carcinoma, since the former is associated with a more favorable prognosis.
 ...
PMID:Clear cell variant of fibrolamellar carcinoma of the liver. 1152 Feb 81

gamma-GT is a membrane-bound enzyme which plays a role in the metabolism of glutathione and facilitates amino-acid transport. gamma-GT is located in several tissues such as the kidney, pancreas and liver. Serum gamma-GT activity is induced by hepatobiliary diseases, especially alcoholic liver diseases and cholestasis, not by renal diseases. Isoenzymes specific for hepatocellular carcinoma are demonstrated by electrophoresis. A new method of measuring serum gamma-GT specific for hepatocellular carcinoma was recently reported.
 ...
PMID:[Gamma-glutamyltranspeptidase (gamma-GT)]. 1179 81

Interleukin-6 (IL-6) binds to a receptor complex consisting of an 80 kDa binding unit (IL-6R) and gp130 responsible for signal transduction. Due to alternative splicing and/or proteolytic digestion IL-6R occurs in soluble form (sIL-6R), as well. Soluble IL-6R is able to bind to gp130 expressing on nucleated cells, thus sIL-6R makes most cells responsive to IL-6. In this study we found that oncostatin M (OSM), an other gp130 dependent cytokine with proliferation inhibitory potential, increases the expression of both membrane-bound IL-6R and sIL-6R generated by alternative splicing in hepatic and mammary carcinoma cell lines. Furthermore, we studied the functional relevance of the presence and binding of soluble IL-6R to HepG2 cells. Using a cDNA expression array, mRNA levels of about 580 human genes were tested by differential display analysis. Our findings suggest, that elevation of surface density of IL-6R by attachment of sIL-6R induces major modulation in gene expression profile of the hepatoma cells. Soluble IL-6R alone has minor effect, it rather decreases expression of some genes, while incubation with IL-6 and sIL-6R together induces major changes in the mRNA pattern of HepG2 cells. These data strongly suggest that presence and binding of soluble cytokine receptors are important elements of inter-cytokine cross talk and affects actual gene expression profile of responding cells.
 ...
PMID:Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells. 1200 38

Hexadecylphosphocholine (HePC) is a synthetic lipid representative of a new group of antiproliferative agents, alkylphosphocholines (APC), which are promising candidates in anticancer therapy. Thus we have studied the action of HePC on the human hepatoblastoma cell line HepG2, which is frequently used as a model for studies into hepatic lipid metabolism. Non-toxic, micromolar concentrations of HePC exerted an antiproliferative effect on this hepatoma cell line. The incorporation into phosphatidylcholine (PC) of the exogenous precursor [methyl-14C]choline was substantially reduced by HePC. This effect was not due to any alteration in choline uptake by the cells, the degradation rate of PC or the release of PC into the culture medium. As anaccumulation of soluble choline derivatives points to CTP:phosphocholine cytidylyltransferase (CT) as the target of HePC activity we examined its effects on the different enzymes involved in the biosynthesis of PC via CDP-choline. Treatment with HePC altered neither the activity of choline kinase (CK) nor that of diacylglycerol cholinephosphotransferase (CPT), but it did inhibit CT activity in HepG2 cells. In vitro HePC also inhibited the activity of cytosolic but not membrane-bound CT. Taken together our results suggest that HePC interferes specifically with the biosynthesis of PC in HepG2 cells by depressing CT translocation to the membrane, which may well impair their proliferation.
 ...
PMID:Hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis and the proliferation of HepG2 cells. 1223 May 78

Interleukin-22 (IL-22), a member of IL-10 family, plays some important roles in immune response through activation of the STAT 3 signal transduction pathway. Two types of IL-22-binding receptor have been discovered, a membrane-bound receptor and a soluble receptor, both encoded by different genes. IL-22 may be involved in inflammatory processes specifically regulated by soluble receptors. By screening a mouse genomic library for a human IL-22 binding protein homologue, we identified the mouse genomic clone of IL-22 binding protein. Its coding sequence was verified and isolated by RT-PCR. The gene encodes a protein of 230 amino acids that share 67.1% amino-acid sequence identity with human IL-22 binding protein. We designated this receptor 'mouse IL-22 binding protein' (mIL-22BP). mIL-22BP could be upregulated by LPS stimulation in mouse monocytes. mIL-22BP binds to mouse and human IL-22 and neutralizes STAT3 activation induced by both cytokines in human and rat hepatoma cell lines. Treating B cells with mouse IL-22 induces production of reactive oxygen species, which mIL-22BP blocks.
 ...
PMID:Cloning and characterization of mouse IL-22 binding protein. 1270 May 95

We have previously reported that direct transfer of the TNF-related apoptosis-inducing ligand (TRAIL) gene resulted in an apoptotic bystander effect, and that this bystander effect was not transferable with cell culture media. To further characterize its mechanism we tested the bystander effect of TRAIL in the human ovarian cancer cell line DOV13, human lung cancer cell line A549, human hepatoma cell line Hepa G2, human breast cancer cell line MDA-MB231 and human colon cancer cell lines Lovo and DLD1. The bystander target cells were transduced with an adenovector expressing the lacZ gene (Ad/CMV-LacZ), while the effector cells were transduced with an adenovector expressing the green fluorescent protein (GFP)/TRAIL fusion gene. Effector and target cells were then cocultured in the same well with or without effector and target cell contact. In all the cell lines tested, target cells were killed if effector and target cell contact was permitted. However, no bystander effect occurred if effector and target cell contact was prevented. Furthermore, the bystander effect and apoptosis induction of TRAIL was dramatically reduced if cells were seeded at a very low density. Moreover, in all the cell lines tested, no detectable soluble TRAIL was found in media from the TRAIL-expressing cell cultures. Together, our results demonstrated that release of soluble TRAIL from transfer of the wild-type TRAIL gene is minimal, and that the bystander effect of the TRAIL gene is mainly mediated by membrane-bound TRAIL on the surface of transduced cells.
 ...
PMID:Cell to cell contact required for bystander effect of the TNF-related apoptosis-inducing ligand (TRAIL) gene. 1273 89


<< Previous 1 2 3 4 5 6 7 8 9 10