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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor stimulated both [3H]thymidine uptake and proliferation of rat AH66 hepatoma cells. However, the increase in cell number was not accompanied by a proportional increase in the levels of alpha-fetoprotein of the culture media. The effects of EGF on the cell proliferation were antagonized by N6,O2'-dibutyryl cAMP.
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PMID:Epidermal growth factor stimulates proliferation of rat hepatoma cells producing alpha-fetoprotein. 9 54

Human hepatic stimulator substance (HSS), an organ-specific and heat-stable factor which differs from insulin, glucagon and EGF, has been partially purified from aborted human fetal livers. It was found to stimulate DNA synthesis of human hepatocytes. AH22 hepatoma cells responded dose-dependently. HSS was also found to enhance the survival of D-GAL intoxicated rats as compared to control (62.5% vs. 26.1%). Our results suggest that human HSS is very similar to that in animals.
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PMID:Effects of human HSS on hepatocyte and hepatoma cell proliferation and D-GAL induced acute liver failure. 133 57

Hsp90 is a heat-shock protein constitutively expressed in most cells. Besides regulation by thermal stress, the expression of hsp90 is also positively regulated by developmental and mitogenic stimuli. The effect of serum and insulin on protein and hsp90 alpha-mRNA levels has been studied in the chicken hepatoma cell line DU249. The culture of cells in serum-free medium resulted in a decrease of hsp90 alpha-mRNA level. A transient increase was observed at 6-9 h after serum restimulation. The expression of hsp90 gene was also increased by insulin alone in a dose-dependent manner and was maximum between 6 and 9 h treatment. The insulin induced increase of hsp90 alpha-mRNA was suppressed by cycloheximide (10 micrograms/ml) but not by an inhibitor of DNA synthesis, demonstrating that this induction requires protein neosynthesis. In serum starved cells, other growth factors (IGF1, EGF and bFGF) showed a positive effect on hsp90 alpha-mRNA level which took place before DNA synthesis with the same time-course as that of insulin. With PDGF, the induction of hsp90 alpha-mRNA occurred earlier. The time interval between the maximum of hsp90 alpha-mRNA induction and that of DNA synthesis was the same for all growth factors studied. From these results, we conclude that growth factors acting via tyrosine kinase receptors up-regulate hsp90 alpha-mRNA level in a DNA synthesis independent manner, possibly in late G1.
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PMID:Growth factors acting via tyrosine kinase receptors induce HSP90 alpha gene expression. 176 67

Expression of epidermal growth factor receptor (EGF-R) in human hepatocellular carcinoma (HCC), hepatoblastoma and non-cancerous liver tissues was investigated immunohistochemically in order to evaluate the possible role of EGF-R expression in neoplastic transformation of hepatocytes. Immunoreactive EGF-R molecules were identified on frozen sections by means of the avidin-biotin immunoperoxidase complex technique using a monoclonal antibody recognizing an epitope of the external domain of human EGF-R. Linear positive staining was present on the surface of carcinoma cells in one hepatoblastoma and in 9 of 11 HCCs. In addition, an enhanced level of surface EGF-R expression was observed on the tumor cells in 9 of 12 cases in comparison with that on hepatocytes in surrounding non-cancerous liver tissue, which in most cases showed chronic inflammation, hepatocyte injury or regeneration. No positive staining in the form of coalescent cytoplasmic granules was present in HCC or hepatoblastoma cells, nor in the cytoplasm of hepatocytes in normal or non-cancerous diseased liver tissue. Little or no reactivity was present on the surface membrane of hepatocytes in the normal liver tissues of 8 control cases. Furthermore, immunoelectron microscopy revealed the localization of this immunoreactive EGF-R molecule on the plasma membrane. Considering that the functional form of EGF-R could be localized on the plasma membrane, the enhanced expression of immunoreactive EGF-R on the tumor cell surface demonstrated here may suggest a possible role of EGF-R in the development or progression of human HCC as well as in hepatocyte regeneration.
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PMID:Immunohistochemical and ultrastructural localization of epidermal growth factor receptor in human liver and hepatocellular carcinoma tissues. 215 2

The anchorage-independent growth of Morris hepatoma 7777 (MH) cells in serum-free medium was examined. The influence of insulin, epidermal growth factor and transforming growth factor beta 1 (TGF-beta 1) on [3H]thymidine incorporation and colony formation of the investigated cells was described. Contrary to normal rat hepatocytes TGF-beta 1 plus EGF and insulin were found to stimulate MH cells proliferation in presented conditions. A simple, chemically-defined culture system suitable for research on mitogenic peptides was proposed.
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PMID:Transforming growth factor-beta 1 stimulates proliferation of Morris hepatoma cells in serum-free soft agar culture system supplemented with EGF and insulin. 220 89

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

A hybrid clone was developed by the fusion of a pluripotent mouse teratocarcinoma cell line PCC-4 AzaR to the Zajdela ascitic hepatoma (ZAH) of rat origin. This hybrid cell line, F2231A, possessed a predominantly teratocarcinoma morphology with a large nucleus and prominent nucleoli, and grew in nests. F2231A cells formed undifferentiated tumours in irradiated Sv/129 mice. It formed aggregates when subcultured at high densities in bacteriological Petri dishes. The hybrid cell line differentiated in response to retinoic acid and also underwent spontaneous differentiation upon overgrowth. Karyological analysis showed the presence of several rat chromosomes in the hybrid and upon isozyme analysis it was found that only the rat variant of the X-linked enzyme HGPRT was expressed. Analysis of the genomic DNA with a cloned probe, specific for rat repetitive sequences, gave strong positive signals in the hepatoma parent and F2231A cells while the parental embryonal carcinoma (EC) cells were negative. The hybrid cell line, like the PCC-4 cells, expressed the SSEA-1 surface marker but not SSEA-3, intercellular fibronectin and EGF receptors. Upon differentiation of F2231A cells there was a loss of expression of SSEA-1. The mRNA for alpha-fetoprotein was expressed by the hybrid cell line and in this respect it resembled the hepatoma parent. Albumin mRNA was not detectable in the hybrid cell line. The mRNA for the transformation-related protein, p53, was expressed at a high level in F2231A cells. The hybrid cell line F2231A retained several of the biochemical and immunological properties of the teratocarcinoma cells.
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PMID:A malignant, stem cell-like somatic hybrid between a mouse teratocarcinoma and a rat ascitic hepatoma is differentiation competent. 247 69

Here we report the development of novel antibodies which specifically react with phosphothreonine residues [anti-(P-Thr)antibodies]. The specificity of the antibodies was assessed in radioimmunoassays where we could demonstrate that half-maximal and maximal binding of the antibodies to plates coated with BSA - P-Thr occurred at serum dilutions of 1:4000 and 1:1000, respectively. P-Thr inhibited antibody binding with a half-maximal effect at 40 microM. P-Ser was 200-fold less potent while P-Tyr was essentially ineffective. Anti-(P-Thr) antibodies could specifically bind to phosphothreonine-containing proteins on Western blots. Using such a procedure we could demonstrate enhanced threonine phosphorylation of the EGF receptor upon treatment of intact unlabeled A431 cells with EGF. We could further demonstrate antibodies binding to proteins present in extracts of rat hepatoma cells (Fao). P-Thr at 10 microM completely inhibited antibody binding while P-Ser, P-Tyr, Thr or Ser, each present at tenfold higher concentrations, had no such inhibitory effect. Anti-(P-Thr) antibodies were also capable of specifically immunoprecipitating 32P-labeled phosphoproteins present in Triton extracts of Fao cells. Immunoprecipitation of proteins of 38 kDa, 55 kDa, 85 kDa, 100 kDa and 155 kDa was inhibited by 1 mM P-Thr but not by P-Tyr. These findings suggest that anti-(P-Thr) antibodies could be powerful tools in studies aimed at monitoring alterations in threonine phosphorylation of specific proteins as they occur under physiological conditions in response to various extracellular stimuli. Identification of such proteins can be conveniently monitored by immunoblotting.
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PMID:Antibodies directed against phosphothreonine residues as potent tools for studying protein phosphorylation. 250 Mar 41

The culture system of hepatocellular carcinoma (HCC) has been established and the effect of hepatotrophic factors on these cell lines have been studied. During this study the effect of the human epidermal growth factor intensifying anti-tumor action of anti-tumor agents will be evaluated. HCC cell lines (C-HC-4, C-HC-20) show logarithmic growth in the serum-free medium. These growth curves after administration of 1 x 10(-12- -8) M of hEGF were measured, and the existence of the hEGF receptors was evaluated using the ABC method. The growth curve of HC-4 transplanted into nude mice was measured in 4 groups; the control group, the hEGF group, the gamma Interferon (gamma IFN) group, and the hEGF + gamma IFN group. The hEGF enhanced the cell growth of C-HC-4 and C-HC-20, and EGF receptors were confirmed immunohistologically. In the hEGF+ gamma IFN group, growth inhibition seems to be most important. The hEGF may intensify the anti-tumor action of the anti-tumor agents.
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PMID:[Development of a new therapeutic method in hepatocellular carcinoma using a culture system--the intensifying effect of human epidermal growth factor (hEGF) on the antitumor action of antitumor agents]. 254 26

We have previously shown that glucocorticoids suppress the proliferation of Fu5 hepatoma cells and have selected subclones which are either hypersensitive (BDS1) or resistant (EDR3) to the antiproliferative effects of dexamethasone, a synthetic glucocorticoid. BDS1 cells externalize a glucocorticoid suppressible mitogenic activity (denoted GSM) which stimulated [3H]thymidine incorporation in quiescent, serum-starved Balb/c 3T3 cells. Glucocorticoid treatment of BDS1 cells reduced the secreted levels of GSM activity by approximately 20-fold in comparison to untreated cells. The GSM activity was constitutively secreted from a glucocorticoid receptor minus variant (EDR3) demonstrating that the suppression of this mitogenic activity is a new glucocorticoid hormone response which required a functional receptor. GSM activity was sensitive to sulfhydryl reducing agents or trypsin, stable to heat and acid treatments and fractionated in gel filtration columns with a native molecular weight of approximately Mr 30,000. The persistence of this size for mitogenic activity after electrophoretic fractionation in nonreducing sodium dodecyl sulfate-poly-acrylamide gels suggested that the GSM activity is comprised of a single protein. Total secreted protein isolated from untreated BDS1, but not dexamethasone-treated BDS1, stimulated 3T3 cells to grow in transformed-appearing large colonies in soft agar and to display multiple layering and elongated spindle-like morphology on solid substratum. The addition of both insulin and EGF to conditioned medium protein isolated from glucocorticoid-treated BDS1 cells restored full induction of 3T3 cell anchorage-independent growth while insulin restored full and EGF partial mitogenic stimulation of these fibroblasts. These results suggest that the GSM activity acts in a pathway common to that of insulin or EGF in fibroblasts.
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PMID:Partial characterization of a glucocorticoid suppressible mitogenic activity secreted from a rat hepatoma cell line hypersensitive to the antiproliferative effects of glucocorticoids. 254 83


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