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)

The regulation of alpha-fetoprotein (AFP) secretion and growth rate by various hormones in established human hepatoma (HuH-7, PLC/PRF/5, huH-1, huH-4, and KIM-1/c-4) and hepatoblastoma (HUH-6 Clone 5) cell lines was studied. These 6 cell lines replicated continuously in a chemically defined medium and secreted 84 ng (HuH-7) to 23 pg (huH-4) AFP per 24 h per 1 X 10(4) cells into the culture medium. The addition of insulin increased the growth rate of all examined cell lines and partially inhibited the AFP secretion in those cell lines except KIM-1/c-4, while the addition of dexamethasone inhibited the growth and stimulated the AFP secretion in all of the cell lines. The addition of 3,3',5-triiodothyronine inhibited the growth of all cell lines; however, different effects on the AFP secretion were observed depending on the cell lines used. Obviously, the AFP secretion was unrelated to the change in growth rate. When dexamethasone and N6-O2-dibutyryl cyclic AMP were added together, the AFP secretion was further stimulated. On the other hand, when dexamethasone and insulin were added simultaneously, the dexamethasone-mediated stimulation of AFP secretions was diminished. The data indicated that the regulatory mechanisms of AFP secretion by the hormones in the established human hepatoma and hepatoblastoma cell lines cannot be deduced according to the results of one cell line.
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PMID:Hormonal control of alpha-fetoprotein secretion in human hepatoma cell lines proliferating in chemically defined medium. 241 43

When enriched large granular lymphocytes (LGLs) were activated by K562 cells substantial amounts of interleukin 1 (IL-1) could be detected in the supernatants as measured by the mouse thymocyte assay. IL-1 could also be produced by LGLs treated with other tumor cells according to their ability to be lysed by LGLs. Therefore PLC/PRF/5 hepatoma cells which were moderately sensitive to LGL attack stimulated moderate amounts of IL-1 from the LGLs. Yac-1 cells and human fibroblasts which are resistant to LGL cytolysis did not activate LGLs to produce significant amounts of IL-1. IL-1 was shown to be produced by LGLs and not by the stimulatory tumor cells. Interferon-alpha (IFN), which reduced the susceptibility of target cells to be lysed by LGLs, also inhibited their ability to stimulate IL-1 production from LGLs. The IL-1 stimulatory effect of tumor cells on LGLs could not be attributed to Mycoplasma or endotoxin contamination. It is suggested that LGLs release IL-1 when they encounter susceptible cells and that release of this cytokine is important in the subsequent lysis of target cells.
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PMID:Tumor cells stimulate interleukin 1 (IL-1) production from enriched large granular lymphocytes. 241 68

Monoclonal antibodies against human alpha-fetoprotein (AFP) or carcinoembryonic antigen (CEA) were conjugated to liposomes containing adriamycin (ADM), and the therapeutic effects of the conjugates were experimentally studied in vitro and in vivo. The liposomes were prepared from a lipid mixture of egg phosphatidyl choline, cholesterol and dipalmitoylphosphatidyl ethanolamine, and were covalently coupled with anti-AFP monoclonal antibody (19-F-12) or anti-CEA monoclonal antibody (1-C-11) after activation of antibody with the N-hydroxysuccinimidyl 8-(2-pyridyldithio) propionate and dithiothreitol. The selective binding of the 19-F-12 conjugated liposomes to AFP-positive human hepatoma cell line PLC and the 1-C-11 conjugated liposomes to CEA-positive colon cancer cell line C-1 as demonstrated using fluorescent liposomes. In vitro studies with PLC and C-1 clearly indicated that monoclonal antibody-conjugated liposomes containing ADM exerted much more effects than unconjugated liposomes containing ADM on target cells in the inhibition assay of [3H]-thymidine incorporation. The therapeutic effects of the conjugates were tested in vivo on AFP-positive human hepatoma xenograft, Li-7, and CEA-positive human colon cancer xenograft, Co-4, maintained in BALB/c nu/nu mice. The antitumor effect of the antibody-conjugated liposomes containing ADM was far greater than that of unconjugated liposomes containing ADM or that of ADM alone as assessed by tumor weight and histological findings.
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PMID:[Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein or anti-carcinoembryonic antigen monoclonal antibodies]. 242 62

The effects of suramin, an antiparasitic agent, upon in vitro hepatitis B surface antigen production by the human hepatoma cell line PLC/PRF/5 and hepatitis B virus associated DNA polymerase activity in the serum of a chronically infected patient were examined. Treatment with suramin resulted in decreases in hepatitis B surface antigen production and hepatitis B-virus associated DNA polymerase activity. The decrease in hepatitis B surface antigen production was paralleled by a general decrease in hepatoma cell viability and cellular protein synthesis. Although the inhibitory effects of suramin for hepatitis B virus appear to be nonspecific as demonstrated in these two in vitro systems, the recently announced trial of suramin for the treatment of the acquired immunodeficiency syndrome should afford an unusual opportunity to evaluate the effectiveness of suramin in the treatment of chronic hepatitis B virus infection.
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PMID:Effects of suramin on in vitro HBsAg production by PLC/PRF/5 cells and hepatitis B virus DNA polymerase activity. 242 68

Alpha-foetoprotein (AFP) synthesis, although repressed in normal adults, is increased in the majority of patients with hepatocellular carcinoma (HCC). We have investigated whether active transcription of the AFP gene may explain raised serum AFP concentrations in patients with HCC and hepatoblastoma by assaying human tumour and non-neoplastic tissue by molecular hybridization for the presence of mRNA encoding AFP. Ten operative HCC and six autopsy HCC specimens, two HCC cell lines, and one hepatoblastoma specimen were examined. Total cellular RNA and poly-(A)+ RNA were extracted and AFP mRNA sequences sought by dot-blot and Northern blot hybridisation to a human cDNA AFP probe. Cellular AFP was localised by avidin-biotin staining. AFP mRNA was detected in 8/10 operative specimens, as well as PLC/PRF/5 nude mouse tumours. Weaker hybridization was detected in 4/6 autopsy specimens. Signals of comparable intensity to that in operative tumours were detected in non-neoplastic tissue of 6 patients. AFP mRNA from nude mouse tumours migrated as a 20S discrete band on agarose gel electrophoresis, whereas a more complex hybridization pattern was evident in human tumours. Positive cytoplasmic immuno-staining for AFP was observed in 4 tumours and 2 corresponding non-neoplastic specimens and in a HCC cell line. In non-neoplastic liver, AFP was localised in cells that appeared dysplastic. Thus steady-state levels of AFP mRNA are detectable in human HCC tissue and surrounding non-neoplastic liver. These findings may prove pertinent to an understanding of the genetic expression of AFP in malignant hepatocytes, and the sequence of events leading to uncontrolled cellular proliferation.
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PMID:Detection of alpha-foetoprotein messenger RNA in human hepatocellular carcinoma and hepatoblastoma tissue. 243 15

When incubated in preconditioned medium, i.e. spent media from the hepatocellular carcinoma (PLC/PRF/5) cell cultures, human embryonic liver (HEL) cells differentiate and acquire oncologic phenotypes. This is caused by transcriptional alterations in fetal gene expression. This occurs when hepatocytes are proliferating rapidly and secreting alpha fetoprotein (AFP), and later when the quiescent state is reached with secretion of albumin (ALB). The present studies examined the parameters signaling oncologic transformation during liver cell differentiation in the conditioned medium. mRNAs coding for AFP, ALB and HBsAg were isolated from HEL, adult liver cells (ADLC) and from PLC/PRF/5 cells, respectively. cDNA molecules complementary to these polysomal mRNA molecules were constructed and labeled with 32P. These tracers were used to quantitate changes in cellular mRNA X AFP, mRNA X ALB and mRNA X HBsAg directly by DNA molecular hybridization during HEL cells cultivation in the preconditioned medium. Under these conditions, the changes in cellular mRNA X HBsAg and mRNA X AFP correlated with an increased tumorigenicity in athymic Nu/Nu mice, membrane galactosyltransferase and phospho-tyrosine kinase activities.
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PMID:Human embryonic liver cell differentiation. I. Changes in specific mRNA synthesis correlates with parameters signaling oncologic alterations. 243 70

Monoclonal antibodies were isolated following immunization with the HBsAg and alpha-fetoprotein-secreting human hepatoma PLC/PRF/5 ("Alexander") cell line. Three antibodies (K-PLC1, K-PLC2 and K-PLC3) showed evidence of carcinoma-associated reactivity by indirect immunofluorescence. Antibodies K-PLC2 and K-PLC3 reacted only with PLC/PRF/5 cells, but not with any other normal or malignant cell type tested, including the Hep/G2 hepatoma cell line. The reactivity of these antibodies was not removed by absorption with homogenates of either normal liver or a primary hepatocellular carcinoma. These results suggest that K-PLC2 and K-PLC3 identify PLC/PRF/5 idiospecific determinants. Following surface iodination of PLC/PRF/5 cells, immunoprecipitation and analysis on polyacrylamide gels, these specific determinants were found to be of 200,000 and 76,000 daltons, respectively. On the other hand, antibody K-PLC1, although unreactive by immunofluorescence on the majority of normal cell types, including those of lymphoid organs and bone marrow liver cells and most epithelia, was weakly positive on some normal ductal secretory epithelia and was positive on vascular endothelium. However, K-PLC1 reacted strongly with all carcinoma specimens tested, and with most carcinoma-derived cell lines, indicating a large increase in K-PLC1 antigen expression by epithelial cells after malignant transformation. Absorption of K-PLC1 with normal liver homogenate had no affect, but absorption with a hepatocarcinoma homogenate abolished its activity. The K-PLC1 antigen could not be immunoblotted or immunoprecipitated and resolved on polyacrylamide gels; yet it showed the properties of a phospholipid, namely resistance to proteases, extractability with organic solvents and sensitivity to phospholipase C.
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PMID:Human hepatocellular carcinoma: cross-reactive and idiotypic antigens associated with malignant transformation of epithelial cells. 243 1

The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease progression remains to be established. In monitoring the response of hepatic metastases, CEA remains the least unsatisfactory marker but should always be used in conjunction with serial ultrasound scans. Tumour markers now play an important role in the diagnosis and monitoring of PLC but a role is also emerging in tumour imaging and drug targeting. The next 20 years should see the introduction of tumour markers of high sensitivity and specificity which make a fundamental contribution not only to detection and monitoring, but also to the effective treatment of liver cancer.
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PMID:Tumour markers in diagnosis and management. 243 83

alpha 1-Microglobulin (alpha 1m) was determined by radio-immunoassay in the supernatants of five human hepatoma cell lines. High amounts of alpha 1m were produced by PLC/PRF/5, intermediate ones by Hep G2 and Hep 3B and very low ones by Malhavu and SK Hepl. alpha 1m isolated from hepatoma cell lines PLC/PRF/5 or Hep G2 supernatants displayed the same physicochemical properties as that purified from human urines: the apparent molecular mass was 26 kDa and the pI from 5.6 to 6.4 as measured after two-dimensional polyacrylamide gel electrophoresis in denaturating conditions; for the native molecule the pI was estimated to be 4.0-4.9. Both urinary and hepatoma alpha 1m migrate as a diffuse band in the alpha zone in agarose gel at pH 8.6 in non-denaturing conditions and present a brown chromophore covalently associated with the molecule. After biosynthetic labelling with [35S]methionine, proteins extracted from hepatoma cell line PLC/PRF/5 and from isolated hepatocytes of human liver were separated by two-dimensional PAGE and transferred to a nitrocellulose membrane. alpha 1m was identified and found to be identical in both cases. However, when compared with the alpha 1m isolated from cell supernatants, less charge heterogeneity but also minor additional spots of higher molecular mass were observed.
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PMID:Purification of alpha 1-microglobulin produced by human hepatoma cell lines. Biochemical characterization and comparison with alpha 1-microglobulin synthesized by human hepatocytes. 243 35

Four human hepatoma cell lines PLC/PRF/5, Hep G2, Sk-Hep 1 and Mahlavu were inoculated subcutaneously into athymic Balb/c nude mice and N/NIH outbred nude rats, producing well encapsulated tumours. The 4 hepatoma tumour types in the athymic rodents differ morphologically. PLC/PRF/5 and Hep G2 cells are well differentiated polygonal cells which resemble normal hepatocytes. Tumour arrangement is characterized by solid masses and trabeculae while stromal support is minimal. In contrast, Mahlavu and Sk-Hep 1 tumours have a sarcomatous appearance and consist of spindle shaped cells arranged in solid masses with a rich stromal support. Tumourigenicity of hepatoma cells in the athymic rodents was dependent on injected cell type, inoculation density, relative immunocompetence of the host and the species of animals used. In nude mice, Sk-Hep 1 cells were the most tumourigenic, while Hep G2 cells were tumourigenic only at very high inoculation densities. In nude rats, which were more resistant to tumour formation, PLC/PRF/5 cells were the most tumourigenic. Pre-treatment of athymic mice and rats with total body irradiation resulted in enhanced tumourigenicity for all hepatoma cell lines tested. This was manifested as increased "take" rates, a decreased latency from tumour cell injection to tumour detection, increased tumour weight, and for PLC/PRF/5 cells an increased invasiveness to adjacent body cavities. Furthermore, following irradiation, the minimal number of injected cells required to produce subcutaneous tumours was markedly reduced in both animal species, regardless of tumour cell type. The protocols described enable the reproducible growth of human hepatoma tumours in athymic rodents.
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PMID:Comparative morphology and tumourigenicity of human hepatocellular carcinoma cell lines in athymic rats and mice. 245 11


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