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)

We report that the concentration of phosphoenolpyruvate carboxykinase (PEPCK) mRNA increased 5- to 10-fold when H4IIEC3 rat hepatoma cells were cultured at high compared to low density. The magnitude and direction of this response were mRNA specific, as the mRNAs encoding tyrosine aminotransferase and albumin increased approximately 20%, whereas the mRNAs encoding beta-actin and alpha-tubulin decreased 40% and 20%, respectively. Paracrine or autocrine mechanisms were not responsible for the density effect, since conditioned medium or frequent medium changes had only a modest effect on the abundance of PEPCK mRNA. Culture of H4IIEC3 cells at low density or on collagen promoted a flattened morphology and low PEPCK mRNA levels. At high density, cells assumed a cuboidal shape on both plastic and collagen and expressed high PEPCK mRNA levels. Induction of PEPCK mRNA by high density culture did not involve increased intracellular cAMP, since treatment with 8-(4-chlorophenylthio)-cAMP was synergistic with density. High cell density increased PEPCK run-on transcription approximately 3-fold, while PEPCK mRNA increased more than 6-fold. These observations suggest that high culture density increases PEPCK mRNA by increasing its transcription and possibly stabilizing PEPCK mRNA. The response could be coupled to the regulation of cell shape, as a close relationship between cell shape and gene expression has previously been shown to be important in the development and maintenance of tissues and organs. The PEPCK gene in H4IIEC3 cells could provide a useful model in which to study the poorly understood mechanisms involved in coordinating form and function.
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PMID:Culture at high density increases phosphoenolpyruvate carboxykinase messenger RNA in H4IIEC3 hepatoma cells. 207 26

The effects of laminin (LAM) and collagen type I (C-I) on human hepatoblastoma (HuH-6) and hepatoma (HuH-7) cell lines were investigated. C-I was superior to LAM in supporting the attachment of the cells, especially of HuH-6, to plastic surfaces. No effect of LAM and C-I on cellular morphology was recognizable by phase contrast microscopy. By scanning electron microscopy (SEM), much more microvilli were found on the cell surface of HuH-6 on LAM substrate than on C-I substrate. In HuH-7 cells, however, these microvilli were rarely found on either LAM substrate or C-I substrate. The gel profile of the proteins secreted by HuH-6 and HuH-7 cells was not affected by the culture substrate except for the major band, though the amount of alpha-fetoprotein (AFP) secreted was larger when the cells were cultured on LAM substrate than on C-I substrate. These results indicate that the ability of LAM or C-I to enhance attachment is different from that to enhance AFP production or microvilli expression in HuH-6 cells and probably in HuH-7 cells.
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PMID:Effects of laminin and collagen type I on the morphology and secretion of proteins in human hepatoblastoma and hepatoma cell lines. 216 81

The activity of serum type IV collagen-degrading enzyme was measured in 21 patients with hepatocellular carcinoma, and the changes in the enzyme activity were investigated with respect to metastasis. The activity of serum type IV collagen-degrading enzyme did not increase until tumor invasion to the portal vein and intrahepatic metastasis were clearly detected ultrasonographically. Activities did not increase during the observation period in patients whose tumor grew slowly and did not invade the portal vein. Thus, the enzyme activity increases in relation to the metastasis of hepatocellular carcinoma and may be useful to detect ongoing metastases.
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PMID:Elevation of serum type IV collagen-degrading enzyme in hepatocellular carcinoma with metastasis. 216 99

In order to identify the most useful marker to diagnose hepatic fibrosis, type III procollagen peptide (P-III-P), laminin P1, and prolyl-hydroxylase (PH) in sera obtained from patients with liver diseases were simultaneously measured and compared with histological features of chronic hepatitis and with tumor size estimated on abdominal CT scan. Further more, the diagnostic accuracy of these markers was evaluated by using discriminant analysis. P-III-P and laminin P1 were closely correlated with the activity of chronic hepatitis. These two markers most accurately discriminated between the compensated stage of liver cirrhosis and the decompensated stage, and between liver cirrhosis and hepatocellular carcinoma. Laminin P1 was found to most clearly distinguish chronic hepatitis from liver cirrhosis. P-III-P was significantly correlated with the size of hepatocellular carcinoma. However, PH failed to discriminate among liver diseases, and showed no significant correlation with a liver tumor size. And none of the markers examined were correlated with a degree of hepatic fibrosis. From these results, the analysis of both serum P-III-P and laminin P1 is a useful approach to evaluate hepatic collagen metabolism.
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PMID:[Assay of serum collagen markers in chronic liver diseases and liver cancer]. 217 Jul 16

Studies were carried out to analyze the mechanism by which extracellular matrix (ECM) molecules and soluble growth factors interplay to control capillary endothelial cell growth. Bovine adrenal capillary endothelial cells attached to purified matrix components but spread poorly and exhibited low levels of DNA synthesis in the absence of exogenous growth factors or serum. Addition of cationic, heparin-binding growth factor purified from either human hepatoma cells or normal bovine pituitary (fibroblast growth factor) induced extensive cell spreading and up to eight fold increases in DNA synthetic rates relative to levels observed in cells on similar substrata in the absence of mitogen. However, the extent of this response differed depending upon the type of ECM molecule used for cell attachment (fold increase on type III collagen greater than gelatin greater than type IV collagen greater than fibronectin greater than type V collagen much greater than laminin). Computerized morphometry demonstrated that endothelial cell DNA synthetic rates increased in an exponential fashion in direct relation to linear increases in cell and nuclear size (projected areas). Similarly sized cells always displayed the same level of DNA synthesis independent of the type of ECM molecule used for cell attachment or the presence of saturating amounts of growth factor. In all cases, DNA metabolism appeared to be coupled to physical expansion of the cell and nucleus rather than to a specific cell morphology (e.g. polygonal versus bipolar). These findings suggest that ECM may act locally as a "solid state" regulator of angiogenesis through its ability to selectively support or prohibit cell and nuclear extension in response to stimulation by soluble mitogens.
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PMID:Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion. 243 64

Hepatocytes were isolated from human fetal liver in order to analyze the direct effects of growth factors and hormones on human hepatocyte proliferation and function. Mechanical fragmentation and then dissociation of fetal liver tissue with a collagenase/dispase mixture resulted in high yield and viability of hepatocytes. Hepatocytes were selected in arginine-free, ornithine-supplemented medium and defined by morphology, albumin production and ornithine uptake into cellular protein. A screen of over twenty growth factors, hormones, mitogenic agents and crude organ and cell extracts for effect on the stimulation of hepatocyte growth revealed that EGF, insulin, dexamethasone, and factors concentrated in bovine neural extract and hepatoma cell-conditioned medium supported attachment, maintenance and growth of hepatocytes on a collagen-coated substratum. The population of cells selected and defined as differentiated hepatocytes had a proliferative potential of about 4 cumulative population doublings. EGF and insulin synergistically stimulated DNA synthesis in the absence of other hormones and growth factors. Although neural extracts enhanced hepatocyte number, no effect on DNA synthesis of neural extracts or purified heparin-binding growth factors from neural extracts could be demonstrated in the absence or presence of defined hormones, hepatoma-conditioned medium or serum. Hepatoma cell-conditioned medium had the largest impact on both hepatocyte cell number and DNA synthesis under all conditions. Dialyzed serum protein (1 mg/ml) at 10 times higher protein concentration had a similar effect to hepatoma cell-conditioned medium (100 micrograms/ml). The results suggest that hepatoma cell conditioned medium may be a concentrated and less complicated source than serum for purification and characterization of additional normal hepatocyte growth factors.
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PMID:Direct analysis of growth factor requirements for isolated human fetal hepatocytes. 244 74

Partial resection of the liver is the only curative treatment for patients with hepatocellular carcinoma associated with severe cirrhosis of the liver. Surgical hemostasis on the cut surface of the cirrhotic liver appears very difficult because of the resultant deep cavity and the marked hemorrhagic diathesis. However, by using the microcrystalline collagen powder and the fibrinogen tissue adhesive, complete hemostasis and prevention of postoperative bleeding can be obtained, with minimal blood loss and hepatic ischemia.
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PMID:Use of microcrystalline collagen powder and fibrinogen tissue adhesive for hemostasis and prevention of rebleeding in patients with hepatocellular carcinoma associated with cirrhosis of the liver. 246 32

Our previous studies have demonstrated that 3-aminobenzamide (3AB), an inhibitor of adenosine diphosphate-ribosyl transferase (ADPRT) could enhance the cytotoxicity (in vitro) and antitumor activity (in vivo) of bleomycin (BLM) A5 and peplomycin (PEP) against S-180, hepatoma and Ehrlich ascites carcinoma (EAC). In this study, it was shown that the inhibition rates (INR's) of S-180 in two experiments were increased from 42.5 and 46.1% to 66.2 and 75.9% when BLM 2.5 mg/kg/day x 8 was combined with 3AB 385.4 mg/kg/day x 8, while the decrease of body weight could not be enhanced. BLM at a dose of 5 mg/kg/day x 8 gave INR's of 64.8 and 75%, similar to the combined group but decreased the body weight more significantly. However, the addition of 3AB 385.4 mg/kg/day to BLM did not increase the acute toxicity of BLM alone. There was no significant difference of change of the body weight and subacute toxicity between the BLM and BLM + 3AB group. There was no difference of peripheral blood white cell count and the pathomorphological and ultrastructural change, wet weight and hydroxyproline content (to reflect the collagen content) of the lung of the mice between BLM alone and BLM + 3AB group. Therefore, the study provided experimental evidences for the reasonable use of nontoxic ADPRT inhibitors in adjunct to the chemotherapy of BLM in cancers.
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PMID:The potentiation of the antitumor activity but not toxicity of bleomycin by 3-aminobenzamide. 248 41

The distribution of fibronectin (FN), laminin (LAM), and collagen IV (Coll IV), three components of the basement membranes (BM), was investigated in human hepatocellular carcinoma (HCC) and the surrounding uninvolved liver and was compared with the grade of differentiation of the tumor. The following three patterns of BM antigens were observed in HCC: (1) peritrabecular or periacinar, (2) pericellular, and (3) stromal-vascular. In the more differentiated tumors, FN, LAM, and Coll IV were observed in a peritrabecular or periacinar pattern whereas a pericellular pattern was only seen with anti-FN antisera that occasionally stained the content of acini. Double staining showed that the four antigens were usually codistributed. Occasionally, however, there was a different distribution along the BM suggesting an heterogeneity in the composition of BM. In the more anaplastic tumors and in the intrahepatic metastasis, BM components were seen around vessels and in the stroma and they were usually fragmented. The finding that FN can be located pericellularly or within acini supports the concept that FN is synthesized, at least in part, by hepatoma cells. The peritrabecular and periacinar location of Coll IV and LAM suggests a sinusoidal cell derivation of these two antigens. The immunohistochemical staining patterns for BM in HCC reflect the differentiation of the tumor, with differentiated tumors showing a relatively intact BM and poorly differentiated tumors showing a sharply defective BM.
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PMID:Distribution of basement membrane components in human hepatocellular carcinoma. 253 55

We have previously shown that insulin-like growth factor II (IGF-II) is produced by bone cells and that IGF-II stimulates cell proliferation and collagen synthesis in bone cells. We now extend these in vitro findings by demonstrating specific IGF-II binding to bone cells derived from newborn mouse calvaria and embryonic chick calvaria. The kinetics of [125I] IGF-II binding in embryonic chick calvaria cells showed time and temperature dependence. Scatchard analysis of [125I]IGF-II binding to chick calvaria cells showed an apparent Kd of 1.4 x 10(-10) M, with a calculated receptor site concentration of 40,000/cell. The specificity characteristics showed that IGF-II was significantly more potent than IGF-I or insulin in displacing IGF-II tracer. Competition for binding of [125I]IGF-II by unlabeled IGF-II showed a dose-dependent displacement between 0.5 and 25 ng/ml. Fifty percent displacement of [125I]IGF-II binding to chick and mouse calvarial cells was achieved at 1-2 ng/ml; 90% of specific binding of [125I]IGF-II was displaceable in the presence of 125 ng/ml of unlabeled IGF-II. IGF-I showed less than 5% cross reactivity for displacement of [125I]IGF-II binding to chick and mouse bone cells. Type II receptor inhibitory antibodies, R-II-PAB1 inhibited the binding of [125I]IGF-II to mouse bone cells and H-35 rat hepatoma cells (which contain type II but not type I receptors) in a dose-dependent manner. R-II-PAB1 also inhibited basal cell proliferation as well as IGF-II-, IGF-I-, and fibroblast growth factor (FGF)-induced cell proliferation in mouse bone cells. In chick calvaria bone cells and TE89 human osteosarcoma cells, R-II-PABI inhibited neither binding of [125I]IGF-II nor IGF-II-induced cell proliferation. These results together with our findings that IGF-II increased chick bone cell proliferation in the presence of maximal doses of IGF-I suggest that at least part of the mitogenic action of IGF-II is mediated through type II rather than type I receptors in bone cells.
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PMID:Characterization of the receptor for insulin-like growth factor II in bone cells. 254 14


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