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)

Germinal cell tumors of the testis were studied for the presence of several tumor-associated antigens. Antisera were produced by immunizing rabbits with the purified antigens of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and hepatoma ferritin. Indirect immunofluorescence on embryonal carcinoma with or without teratoma components demonstrated that their staining range was 1--60 per cent with antiserum against AFP, 0--16 per cent with anti-serum against ferritin, and 0-40% with antiserum against CEA. Ferritin-like substances have not been described previously in germinal tumors of the testis. No staining was seen with seminoma cells or benign testicular tissues. Raised serum levels of AFP and the ferritin-like substance were related both to the presence of tumor and to dissemination of the disease. CEA occurred transiently in serum. Eleven patients with primary tumors had no antigen in their sera and have all survived, but the median survival time for 8 patients with either antigen in preoperative sera was 12 months. Five patients with advanced tumor in whom neither AFP nor ferritin was detected had a much longer median survival time (58 mo) than did 13 patients with high levels of serum AFP or ferritin (12 mo). The presence of either AFP or ferritin in sera of patients with primary or advanced disease, therefore, seemed to indicate a poor prognosis. The determination of both substances in serum may be useful in the follow-up of patients with certain types of testicular tumors. The proportion of cells containing each antigen varied in the different tumors. Similarly, each antigen could occur independently in serum. This suggested that certain germ cell tumors contained subpopulations of cells, which differed in their production and release of the antigens studied.
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PMID:Multiple antigens as marker substances in germinal tumors of the testis. 6 76

The present experiment was undertaken to study what types of human cancers are responsive to the antiproliferative effects of suramin. The human malignant cells used were as follows: cervical cancer (HeLa), mammary cancer (MCF-7), bladder cancer (EJ), hepatoma (HuH-7, PLC/PRF/5), embryonal carcinoma (PA-1), in vitro transformed fibroblasts (KMST-6, SUSM-1, VA-13), five myeloma cell lines (KMM-1, KMS-5, KMS-11, KMS-12, RPMI 8226), Burkitt's lymphoma (Raji), acute promyelocytic leukemia (HL-60), chronic myelocytic leukemia (K562), Epstein-Barr virus nuclear antigen positive lymphoblastoid cells (KMS-9). The cells were treated with 25 to 100 micrograms/ml suramin for 72h. Proliferation of HuH-7 and two human myeloma cells (KMS-11 and KMS-12) was remarkably inhibited, and that of PA-1, PLC/PRF/5, KMST-6, two other myeloma cell lines (KMM-1 and KMS-5), Raji and HL-60, was moderately inhibited. In order to confirm part of the results obtained from in vitro experiments, in vivo experiments were also undertaken. The growth of HuH-7 cells transplanted subcutaneously into nude mice was significantly suppressed by intravenous injection of suramin. We discussed the possibility that certain types of human cancers, the growth of which seemed to be more or less dependent on polypeptide growth factors, might be sensitive to the antiproliferative effects of suramin.
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PMID:Antiproliferative effects of suramin on human cancer cells in vitro and in vivo. 148 40

We adapted a method for evaluating monoclonal antibody specificity toward isoforms and examined 29 alpha-fetoprotein (AFP) antibodies from Hybritech. These antibodies were separated by affinity electrophoresis on agarose-containing erythroagglutinating phytohemagglutinin (PHA-E) followed by immunoblotting onto nitrocellulose. Under these conditions, AFP separates into four subfractions: NR (nonreactive with PHA-E), WR (reactive weakly), RS2 (strongly reactive), and RS1 (very strongly reactive). When polyclonal goat anti-AFP control was used as the test antibody, the distribution of amniotic fluid AFP was approximately 50%, 31%, 12%, and 7% for NR, WR, RS2, and RS1, respectively. The distribution for these same bands from the serum of a patient with hepatocellular carcinoma was 39%, 31%, 30%, and 0%; from the serum of a patient with embryonal carcinoma, it was 29%, 38%, 0%, and 33%, respectively. Twenty-six monoclonal antibodies, including the two used in the Hybritech Tandem-E assay for AFP, showed similar distribution, while the remaining three antibodies showed no reactivity to any of the AFP antigens in this system. Although we were not able to demonstrate any specificity of these antisera toward any single AFP isoform, use of this affinity electrophoresis system provides a model for studying isoform specificity of other AFP antibodies and other antibody-antigen systems.
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PMID:Screening antisera for subtype specificity based on immunoblotting of lectin-affinity electrophoresis: application toward alpha-fetoprotein subfractions. 169 37

Suramin, a polyanionic compound used clinically for the treatment of African trypanosomiosis and onchocerciasis, has been shown to inhibit the action of various growth factors such as platelet-derived growth factor, epidermal growth factor, fibroblast growth factor and transforming growth factor-beta to stimulate DNA synthesis of cells. Therefore, we investigated effects of suramin on cell proliferation of various types of human malignant cells in culture. Cell lines used were as follows: cervical cancer (HeLa), mammary cancer (MCF-7), bladder cancer (EJ), hepatoma (HuH-7, PLC/PRF/5), embryonal carcinoma (PA-1), and three in vitro transformed human fibroblast lines (KMST-6, SUSM-1, and VA-13). A serum-free defined medium, ASF103, was used when the effect of suramin on proliferation of cells was investigated. This culture medium contains only bovine serum albumin (0.1%), transferrin (5 micrograms/ml) and insulin (5 micrograms/ml) as peptide factors. On day 1, the drug was added to culture medium at the concentration of 25-100 micrograms/ml and 72-96 hr later, the number of cells was counted. The growth inhibition was expressed as the percentage of cells surviving after treatment of cells with suramin, with survival in the control condition representing 100 percent. Proliferation of HuH-7 cells was prominently inhibited and those of PA-1, PLC/PRF/5 and KMST-6 were moderately inhibited under the same conditions of treatment. On the other hand, other five cell lines were not responsive to up to 100 micrograms/ml suramin.
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PMID:[Effects of suramin on cell proliferation of various types of human malignant cells]. 184 19

Monoclonal antibodies with fine specificities distinguishing alpha-fetoproteins of hepatoma (HEP-AFP) and yolk sac tumor (YST-AFP) origin have been obtained. These murine antibodies were produced by hybridomas made by fusion of X63-Ag8.653 myeloma cells with BALB/c spleen cells immunized with either HEP-AFP or YST-AFP and selected for their differential association with these antigens on the basis of Scatchard plot analysis. Three monoclonals (MA120, MA132 and MA136) selectively reacted with HEP-AFP. Their reactivity with YST-AFP was low. One monoclonal (MA122) reacted strongly with YST-AFP, whereas the reaction with HEP-AFP was significantly less strong. The difference in the association constants of these antibodies for the two AFPs appeared to be due to their specificity for the carbohydrate portions of the AFPs, which are different, at least in part. Indirect immunoperoxidase staining confirmed that MA122 was able to stain sections of an infantile embryonal carcinoma, but not of hepatoma.
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PMID:Monoclonal antibodies with fine specificities distinguishing alpha-fetoproteins of hepatoma and yolk sac tumor origin. 243 Sep 23

Multiple cis-acting regulatory elements consisting of three cellular enhancers and a proximal promoter element have been identified in the region upstream of the mouse alpha-fetoprotein (AFP) gene. We examined the role of these sequences during differentiation by the introduction of modified AFP genes into cells at different stages of commitment to its expression. Modified AFP genes introduced stably into F9 embryonal carcinoma stem cells by DNA transfection were silent until activated by treatment with retinoic acid to form visceral endoderm. Their activation required the presence of both the enhancer and proximal promoter domains. The introduced genes activated simultaneously with the endogenous AFP genes, but reached maximal levels of expression more rapidly, suggesting a greater initial accessibility to transcription factors. In contrast, when modified AFP genes were stably introduced into HepG2 cells, a human hepatoma cell line that constitutively expresses the AFP gene, the proximal promoter sequences were sufficient to direct a low level of expression. The absolute requirement for the AFP enhancers in F9 cells but not in HepG2 cells supports a model by which there is an obligate requirement for enhancers during differentiation in addition to their role in enhancing gene expression after differentiation.
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PMID:Differential requirements for cellular enhancers in stem and differentiated cells. 244 54

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

Previous studies have demonstrated that mouse embryonal carcinoma (EC) cells produce at least two growth factors: one related to platelet-derived growth factor (PDGF) and another related to basic fibroblast growth factor (FGFb). Since human EC cell lines are being used with increased frequency, the current study examined whether human EC cells produce growth factors, in particular those produced by mouse EC cells. In this study, it was determined that the human EC cell line NT2/D1 produces a heat-labile heparin-binding growth factor that behaves like FGF in a bioassay. Three additional criteria suggest that this factor is closely related or identical to FGFb. The factor from NT2/D1 EC cells, bovine FGFb and FGFb produced by the human hepatoma cell line SK-HEP-1 elute from heparin at similar salt concentrations. The factor produced by NT2/D1 EC cells exhibits a thermal stability curve that is nearly identical to those for bovine FGFb and FGFb from SK-HEP-1 cells. Lastly, NT2/D1 and SK-HEP-1 cells express transcripts of the same size that hybridize with a cDNA probe for human FGFb. In the course of these studies it was determined that NT2/D1 EC cells also express several transcripts that hybridize with a cDNA probe for the human PDGF A-chain. Thus, our findings suggest that the pattern of growth factor production by human and mouse EC cells is evolutionarily conserved.
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PMID:Production of growth factors related to fibroblast growth factor and platelet-derived growth factor by human embryonal carcinoma cells. 320 87

This editorial calls for development of quantitative assays for alpha fetoprotein (AFP) which incorporate a long-overdue uniform international standard for AFP. Statistics for presently available detection techniques are reviewed; Double-gel diffusion detects serum AFP in 1/3 white hepatoma patients and 1/3 embryonal gonadal teratoblastomas. Counterimmunoelectophoresis and electroimmunodiffusion detect AFP in more than 50% of white patients with hepatoma and a higher percentage of other racial groups. Sensitive radioimmunoassays (RIAs) can detect AFP in 85-95% of hepatoma patients; the other 5-15% are considered at present not to have AFP-producing tumors. RIAs also discern AFP in 2 other conditions; 1) gastrointestinal tract tumors and entodermally derived tumors; and 2) acute viral hepatitis. AFP in newborns is usually 1-5 mg/100 ml of blood. This level decreases (half-life, 3-5 days) during neonatancy to undetectable levels. AFP is elevated in children with 3 conditions: 1) hepatocellular carcinoma of hepatoblastoma; 2) gonadal teratoblastomas or embryonal carcinoma; and 3) ataxia telangiectasia, but not in other immune deficiency diseases. During gestation, fetal serum AFP reaches a 200-400 mg/100 ml of blood peak in the first trimester which drops to less than 5 mg/100 in newborn unbilical blood. Elevated maternal serum AFP has been shown to mark fetal distress and other pregnancy complications; these amounts are measured in nanorams and require sensitivity.
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PMID:Editorial: Alpha 1-fetoprotein: need for quantitative assays. 412 24

Murine extra-embryonic endodermal cell lines derived from either teratocarcinomas or mouse embryos contain a cytoskeletal protein (Endo A) of Mr = 55,000. Endo A was immunoprecipitated from [35S]methionine-labeled lysates of three parietal endodermal cell lines, A presumptive visceral endodermal cell line, and a fetal hepatoma cell line, but not from fibroblasts, myoblasts, erythroleukemic cells, neuroblastoma cells, keratinocytes, or embryonal carcinoma cells. Embryonal carcinoma cells induced to differentiate by exposure to retinoic acid synthesized increased amounts of Endo A approximately 48 h after exposure to the inducer. Two-dimensional gel analysis of immunoprecipitated samples confirmed that Endo A is distinct from vimentin and murine keratinocyte proteins recognized by two different keratin antisera. Comparison by two-dimensional gel electrophoresis of immunoprecipitated Endo A labeled with either [35S]methionine or [32P]orthophosphate indicated that the multiple forms of Endo A resolved by isoelectric focusing were due, at least in part, to phosphorylation. Serine was identified as the phosphorylated amino acid. Endo A was the only major antigenic protein found in a parietal endodermal cell line which was recognized by a monoclonal antibody prepared by other investigators against trophoblast cytoskeletons. The results indicate that Endo A, like the previously described Endo B protein, is distinct from other cytoskeletal proteins and will be useful as a marker of the differentiation of murine embryonal carcinoma cells to extra-embryonic endoderm.
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PMID:Developmental expression of murine extra-embryonic endodermal cytoskeletal proteins. 617 20


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