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)

Normal rat liver cells (BRL-1) that respond to isoproterenol (beta+2), prostaglandin E1 (PGE+1) and adenosine (Ado+) with a rise in adenosine 3':5'-monophosphate (cAMP) content have been hybridized with rat hepatoma cells (H35) which do not respond to any of these agonists (beta-2, PGE-1 and Ado-). Both the initial hybrid line (BF5) and a subclone (BF5-1-1) expressed a beta+2, PGE+1, Ado- phenotype. However, full expression of the responsive phenotype in the BF5 line was apparent only if phosphodiesterase activity was blocked, for example, by methylisobutylxanthine (MIX). Direct measurements showed the rate of degradation of cAMP to be 7 times greater in intact BF5 cells than in the BRL-1 parent. In contrast to BF5 cells, the BF5-1-1 cells did not express maximal responsiveness to any of the agonists even in the presence of MIX. The differential accumulation of intracellular cAMP observed with BRL-1, BF5 and BF5-1-1 cells in response to isoproterenol was shown not to be as a result of differential rates of excretion of cAMP. Furthermore, no differences in the apparent affinities of the beta 2-catecholamine receptors for isoproterenol were observed. It is suggested that the increased degradative capacity of BF5 cells accounts for the difference in cAMP accumulation in these cells compared with the BRL-1 parent. The reduced responsiveness of BF5-1-1 cells, however, does not appear to be solely due to increased phosphodiesterase activity. It appears that the beta 2- phenotype may not always be dominant in hybrid crosses of this type as has been reported previously.
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PMID:Expression of the regulation of cAMP metabolism in somatic cell hybrids. 9 76

The ability of isoproterenol, glucagon, PGE1 and cholera toxin to stimulate the synthesis of cAMP and protein kinase activity in line of liver cells (BRL) and a line of rat hepatoma cells (H35) has been determined. The concentration of cAMP in BRL cells (approximately 10 pmoles/mg protein) is in the range reported for other cultured cell lines but H35 cells contain extraordinarily low amounts of this cyclic nucleotide (approximately 0.05 pmoles/mg protein). Isoproterenol and PGE1 caused an increase in cAMP content, and protein kinase activation in BRL cells, although glucagon was ineffective. H35 cells, in contrast, were completely insensitive to all hormonal agonists. Despite this fact, cholera toxin was able to produce a marked increase in cAMP content, adenylate cyclase activity and protein kinase activation in H35 cells. binding studies with [125 I]-iodohydroxybenzylpindolol, a specific beta-adrenergic receptor antagonist, revealed that each H35 cell possesses fewer than 10 beta-adrenergic receptors whereas BRL cells contain 2-5,000 receptors per cell. The low level of cAMP in H35 cells appears to result from a combination of totally unstimulated adenylate cyclase and apparently elevated phosphodiesterase activities.
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PMID:Studies of cAMP metabolism in cultured hepatoma cells: presence of functional adenylate cyclase despite low cAMP content and lack of hormonal responsiveness. 20 52

The bioavailability and action of the insulin-like growth factors (IGFs) are determined by specific IGF-binding proteins (IGFBP) to which they are complexed. Complementary DNA clones have been isolated that encode three related IGFBPs: human IGFBP-1 (hIGFBP-1), human IGFBP-3 (hIGFBP-3), and rat IGFBP-2 (rIGFBP-2). IGFBP-1 and IGFBP-3 are regulated differently in human plasma, suggesting that they have different functions. In order to study the molecular basis of the regulation of the different IGFBPs, we have identified a panel of rat cell lines that express a single predominant binding protein and developed an assay strategy to distinguish the different binding proteins. Proteins in conditioned medium were examined by ligand blotting, and by immunoprecipitation and immunoblotting using antibodies to rIGFBP-2 and hIGFBP-1; RNAs were hybridized to cDNA probes for rIGFBP-2 and hIGFBP-1. 1) C6 glial cells and B104 neuroblastoma cells express an approximately 40 kilodalton (kDa) glycosylated binding protein that most likely represents rIGFBP-3, the binding subunit of the 150 kDa IGF: binding protein complex in adult rat serum. The C6 and B104 binding proteins do not react with antibodies to rIGFBP-2, and RNAs from C6 and B104 cells do not hybridize to cDNA probes for rIGFBP-2 or hIGFBP-1. 2) BRL-3A, Clone 9, and TRL 12-15 cell lines derived from normal rat liver express rIGFBP-2, a 30 kDa nonglycosylated IGF-binding protein that is recognized by antibodies to rIGFBP-2 but not by antibodies to hIGFBP-1. RNAs from these cells hybridize to a rIGFBP-2 cDNA probe, but not to a hIGFBP-1 probe. 3) H35 rat hepatoma cells express a 30 kDa nonglycosylated IGFBP that is presumptively identified as rIGFBP-1. It does not react with antibodies to rIGFBP-2, but is recognized by polyclonal and monoclonal antibodies to hIGFBP-1. RNA from H35 cells hybridizes to a hIGFBP-1 cDNA probe, but not to a rIGFBP-2 probe. Expression of rIGFBP-1 by the H35 cell line has enabled us to establish and validate specific assays for this protein that allow us to study its regulation in intact rats. Identification of a panel of rat cell lines expressing specific IGFBPs should be useful in elucidating the molecular mechanisms of IGFBP regulation.
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PMID:Identification of rat cell lines that preferentially express insulin-like growth factor binding proteins rlGFBP-1, 2, or 3. 169 42

Neoplastic transformation of rat liver cells in vitro by DNA-mediated gene transfer with an oncogene, hhcM, derived from human (Mahlavu) hepatocellular carcinoma, is described and compared with that of NIH3T3 cells. hhcM was cloned in a neomycin-resistant simian virus 40 promoter vector (pNeor/S) and was designated pNrpM-1. BRL-1 or NIH3T3 cells, transfected with pNrpM-1 DNA, showed significant morphological changes, loss of contact inhibition, and anchorage-independent growth. They became highly tumorigenic in nude rats and nu/nu mice. Control BRL-1 and NIH3T3 cells, whether transfected with pNeor/S DNA or not, remained contact inhibited and nontumorigenic. Both the transformants and the tumor cells contained integrated hhcM DNA as shown by Southern blot hybridization. The complete nucleotide sequence of the hhcM 3.0-kilobase DNA was also determined, and it consisted of a possible open reading frame for a protein of 52 kilodaltons (467 amino acids). The high-level production of a slightly modified form of this 52-kilodalton protein in a bacterial expression system has been successfully achieved. The bacteria-produced protein was similar in electrophoretic behavior to the 52- to 53-kilodalton protein synthesized in a cell-free translation system using rabbit reticulocyte lysate programmed with hybrid-selected hhcM-specific mRNA from Mahlavu hepatocellular carcinoma cells.
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PMID:A human hepatocellular carcinoma 3.0-kilobase DNA sequence transforms both rat liver cells and NIH3T3 fibroblasts and encodes a 52-kilodalton protein. 216 64

We previously identified a naturally occurring peptide fragment derived from the carboxyl terminal region of the E-domain of pro-insulin-like growth factor II (proIGF-II117-156) in medium conditioned by cultured BRL-3A rat liver cells. In the present study we utilized a radioimmunoassay (RIA) for this peptide to measure physiological concentrations of the peptide in media and serum. Serum levels of the E-domain peptide were very high in the 5-day neonatal rat and declined thereafter to reach low levels in adult rat serum. Chromatography of adult rat serum on Sephadex G-75 in 1 M acetic acid yielded a single broad peak of E-peptide immunoreactivity that coeluted with a synthetic E-peptide standard. However, chromatography of day 5 neonatal rat serum on Sephadex G-75 yielded two peaks of immunoreactivity. One of the peaks coeluted with a synthetic E-peptide standard, whereas the other peak eluted in a region where higher molecular weight proteins typically elute. Experiments aimed at determining whether adult rat serum contained a binding protein for the E-domain peptide revealed that: (1) serum contains little, if any, binding protein for the E-domain peptide, (2) serum contains a proteinase activity that degrades the E-domain peptide, and (3) the proteinase activity can be eliminated by acetic acid/ethanol extraction. Of several rat cell lines tested (BRL-3A, rat embryo fibroblasts (REF), hepatoma cell lines (H4, HTC), GH3 pituitary tumor cells, and normal rat kidney fibroblasts (NRK], only BRL-3A and REF cells secreted measurable E-domain peptide into the medium. In addition, it was found that some component(s) of serum could stimulate secretion of E-domain peptide from BRL-3A and REF cells. Chromatography of the immunoreactivity from BRL-3A and REF-conditioned media on Sephadex G-75 in 1 M acetic acid yielded a single peak that coeluted with a synthetic E-domain peptide standard. Since secretion of the E-domain peptide parallels the expression of IGF-II, the RIA for the proIGF-II E-domain peptide may be useful for studies of the biosynthesis and secretion of IGF-II under different physiological conditions. The RIA for the IGF-II E-domain peptide has two technical advantages over the RIA for IGF-II, namely, the lack of interference by IGF binding proteins and the relative ease with which large quantities of pure antigen can be synthesized.
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PMID:The E-domain peptide of rat pro-insulin-like growth factor II (proIGF-II): properties of the peptide in serum and production by rat cell lines. 229 41

A protein preparation that specifically binds insulin-like growth factors (IGFs) I and II was purified from medium conditioned by rat liver BRL-3A cells using molecular sieve chromatography in 1 M acetic acid followed by affinity chromatography on IGF-II-agarose. The affinity-purified IGF-binding protein exhibits a single major band with apparent Mr = 36,300 under reducing conditions on sodium dodecyl sulfate-polyacrylamide gels. The IGF-binding protein is efficiently and specifically cross-linked to either 125I-IGF-I (human) or 125I-IGF-II (rat) using disuccinimidyl suberate. An IGF-binding protein of similar apparent molecular weight was also affinity purified from rat hepatoma H-35 cell conditioned medium and found to differ from the BRL-3A protein such that potent polyclonal antisera prepared in rabbits against the purified BRL-3A IGF-binding protein exhibited a much lower titer for the H-35 protein in an enzyme-linked immunosorbent assay and upon immunoblotting. In order to determine whether a single BRL-3A IGF-binding protein is present in the affinity-purified preparation, the protein was prepared for sequencing on a Sephacryl S-300 column in 6 M guanidine HCl after reduction and alkylation. The amino acid composition (expressed in percentages) of this IGF-binding protein was determined to be: Cys = 5.5, Lys = 4.8, His = 2.8, Arg = 7.8, Asx = 10.2, Thr = 5.1, Ser = 3.9, Glx = 15.7, Gly = 17.4, Ala = 7.3, Val = 4.6, Met = 1.4, Ile = 2.4, Leu = 8.3, Tyr = 1.0, Phe = 1.9. Sequencing of the NH2-terminal portion of this protein led to the identification of 31 amino acids in the following order: Phe-Arg-Cys-Pro-Pro-Cys-Thr-Pro-Glu-Arg-Leu-Ala-Ala-Cys-Gly-Pro-Pro-Pro- Asp-Ala-Pro-Cys-Ala-Glu-Leu-Val-Arg-Glu-Pro-Gly-Cys. We conclude that rat liver BRL-3A cells secrete a single major IGF-binding protein capable of binding both IGF-I and IGF-II.
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PMID:Purification and amino-terminal sequence of an insulin-like growth factor-binding protein secreted by rat liver BRL-3A cells. 242 67

The primary structure of an insulin-like growth factor (IGF) binding protein produced by human HEP G2 hepatoma cells has been deduced from the cDNA sequence. The 234 amino acid protein has a predicted molecular mass of 25,274 and contains a single, distinctive cysteine-rich region. The N-terminal sequence of this protein is quite similar to the limited sequence data available for a rat IGF binding protein produced by BRL-3A cells and suggests a common ancestral origin. In contrast, the HEP G2 IGF binding protein sequence bears no similarity to the N-terminal 15 amino acids of a 53 kilodalton binding protein purified from human plasma. Comparison of full-length protein sequences for the IGF-I and IGF-II receptors with that of the HEP G2 IGF binding protein also fails to demonstrate any significant similarities among these three proteins, and suggests that each contains a unique binding domain for the IGF peptides.
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PMID:Insulin-like growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-I and IGF-II receptors. 245 22

TGF beta is a potent, nontoxic inhibitor of mitogen-induced DNA synthesis in primary cultures of adult rat hepatocytes. Using a cDNA probe, we investigated TGF beta gene expression in quiescent, regenerating, and neoplastic liver, and several hepatoma lines by Northern gel analysis. We found that regenerating liver had increased TGF beta gene transcripts beginning at about 8 h, with a broad peak of 48-120 h and return to normal after 9 days. Separation of the regenerating liver into its constituent cell types, followed by RNA extraction and reprobing, revealed that increased TGF beta gene transcripts were confined to the enriched endothelial-cell population and not the hepatocytes. Increased hepatic TGF beta expression was also found in fetal liver and in rats immediately after birth. Elevated TGF beta mRNA levels were also found in primary cultures of oval cells and an established bile ductular cell line, as well as in carcinogen-altered liver epithelial cell lines. Transcripts were undetectable in normal human liver but were abundant in the human hepatoma lines Hep G2, Hep 3B, PLC/PRF/5, and SK-Hep-1. Elevated levels were also found in the normal rat liver-derived lines BRL-3A and clone 9 and the H4IIE rat hepatoma, but not in the HTC, MH1C1, and MH7777 rat hepatomas. The hepatocarcinogen diethylnitrosamine induced high transcript levels after single injections in a time- and dose-dependent manner. These results suggest that the liver may be a paracrine organ with respect to TGF beta gene expression, which can be induced by carcinogens and by growth stimulation.
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PMID:TGF beta gene transcription in normal and neoplastic liver growth. 272 73

A 50-year-old Japanese man had had abscesses and draining fistulas in the perianal region. These lesions recurred, despite surgical treatment such as incision and drainage over a 30 year period. "Sulfur granules" were found in the pus from the abscess and Actinomyces israelii was cultured. Ampicillin-cloxacillin treatment lead to healing. The patient died 4 months later with a hepatoma and multiple metastases.
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PMID:Primary perianal actinomycosis over a thirty year period. 377 63

Ampicillin bioavailability was examined using the urinary excretion method, in healthy subjects and patients with: viral hepatitis, primary hepatocellular carcinoma and hepatosplenic schistosomiasis. A single dose of 500 mg ampicillin was administered intravenously in each case. Viral hepatitis patients gave similar results to healthy subjects. Primary hepatocellular carcinoma and hepatosplenic schistosomiasis patients had reduced drug bioavailability compared to healthy subjects (P less than 0.001).
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PMID:Investigations on the influence of liver diseases on ampicillin body levels in man. 403 May 36


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