Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of leukoregulin, a 50-kD lymphokine with unique antitumor properties, was studied in vitro on several fibroblast functions. Leukoregulin did not inhibit fibroblast proliferation, as measured by cell enumeration and [3H]thymidine incorporation, and had no cytotoxic effect in terms of increased membrane permeability detected by trypan blue exclusion, two of the major leukoregulin actions on tumor cells. Leukoregulin induced a dose-dependent decrease in collagen synthesis, demonstrated by decreased [3H]proline incorporation into collagenase-digestible protein, as early as 6 h after the addition of the lymphokine to human fibroblasts. Leukoregulin inhibited the synthesis of both type I and type III collagen, as measured by SDS-PAGE and by specific radioimmunoassay. Neutralizing antibodies to interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma failed to alter the effect of leukoregulin on collagen synthesis, attesting that leukoregulin action was not due to contamination by these cytokines. Inhibition of collagen synthesis occurred concomitantly with increased secretion of prostaglandin E2 and a transient rise in intracellular cyclic AMP content, peaking at 6 h. However, blocking prostaglandin synthesis with indomethacin did not counteract inhibition of collagen synthesis by leukoregulin, demonstrating independence of this action of leukoregulin from cyclooxygenase metabolites. Leukoregulin also stimulated glycosaminoglycan production in a dose-dependent manner, affecting the synthesis of hyaluronic acid as the major fibroblast-derived extracellular glycosaminoglycan. In addition, secretion of neutral proteases (collagenase, elastase, caseinase) was increased. These observations indicate that leukoregulin is able to regulate synthesis of molecules critical to the deposition of the extracellular matrix by nontransformed nonmalignant fibroblasts.
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PMID:Modulation of human dermal fibroblast extracellular matrix metabolism by the lymphokine leukoregulin. 164 5

To gain insight into the activity of cytosolic proteases in tumors, the ATP-dependent proteolysis of cell sap and the ATP- and ubiquitin-dependent proteolysis of Fraction II (a cytosolic subfraction freed of endogenous ubiquitin) were measured in the anaplastic Yoshida ascites hepatoma AH 130. Hepatoma cell sap showed only low, although significant, ATP-stimulated proteolysis, as best seen by comparisons with rat liver made on the basis of wet weight. Much of the basal proteolytic activity of cell sap and of its subfraction enriched in high Mr complexes (Fraction X) peaked near 18S in sucrose gradients. In contrast with cell sap, Fraction II from hepatoma degraded [14C]methylcasein more efficiently than Fraction II from normal liver, but the activities for liver and tumor did not differ on a wet weight basis. Altered polypeptide patterns shown by SDS-PAGE in the Yoshida hepatoma suggested that some abundant hepatoma-specific cytosolic protein might interfere with degradation of the [14C]methylcasein by hepatoma.
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PMID:ATP- and ATP+ ubiquitin-stimulated proteolysis in rat liver and Yoshida ascites hepatoma. 165 48

Metalloproteinase inhibitors were surveyed with the culture media of 19 kinds of human tumor cell lines, using transin (rat stromelysin) as the target enzyme. This survey showed that most of the cell lines more or less secreted inhibitor activity, and that a human hepatoma cell line, HLE, secreted an extremely high inhibitor activity into the culture medium. Two kinds of metalloproteinase inhibitors were purified from the serum-free conditioned medium of HLE cells. The major inhibitor, which showed a single protein band with a molecular weight (Mr) of 21,000 (21k) (nonreduced) or 24k (reduced) on SDS-polyacrylamide gel electrophoresis, was identified as TIMP-2 (tissue inhibitor of metalloproteinases-2) by the analysis of its N-terminal amino acid sequence. The other was immunologically identified as TIMP. Purified TIMP-2 inhibited the activities of transin, matrin (pump-1), Mr 72k gelatinase, and interstitial collagenase with 1:1 stoichiometry. When the latent precursor form (Mr 57k) of transin was incubated with p-aminophenylmercuric acetate as an activating reagent, TIMP-2 inhibited the conversion of the intermediate form (Mr 45k) into the mature enzyme (Mr 42k). This indicated that TIMP-2 regulates not only the activity of the mature enzyme but also the autolytic processing of the proenzyme. TIMP-2 also inhibited in vitro tumor invasion through reconstituted basement membrane (matrigel) in chemotaxis chambers, showing that the metalloproteinase inhibitors as well as the extracellular matrix metalloproteinases are involved in tumor invasion through basement membrane and other extracellular matrices.
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PMID:Efficient purification of TIMP-2 from culture medium conditioned by human hepatoma cell line, and its inhibitory effects on metalloproteinases and in vitro tumor invasion. 166 1

Peroxidase was studied as a developmental marker in pumpkin (Cucurbita pepo L.) callus lines and horse-radish (Armoracia lapathifolia Gilib) transformants. Embryogenic callus lines DE grown on MS medium with 2.4-D and NA-3 grown on medium with NAA and adenine sulfate showed about a 20 times higher enzyme activity than the habituated non-embryogenic line Z5b/T grown on medium without hormones. A rise in peroxidase activity indicated that somatic embryogenesis was triggered in a few habituated tissue cultures. Separated globular embryoids had a manifold lower enzyme activity than the callus from which they originated. SDS-electrophoresis showed distinct polypeptide patterns between the horse-radish leaves and crown galls, but the tumor characteristic protein bands failed to be identified. In horse-radish crown galls and short bushy plants regenerated from hairy roots an enhanced peroxidase activity was registered. Due to its high peroxidase level and abundant biomass production horse-radish transformants should facilitate enzyme production.
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PMID:Peroxidase as a developmental marker in plant tissue culture. 166 82

Alpha fetoprotein (AFP) is present at high concentrations in fetal fluids, certain neoplasias, and regenerating liver. Its physiological function remains largely unknown. Using a primary monolayer culture system, we investigated the proliferative activity of human (h) cord blood (CB) and highly purified AFP. hAFP, purified from hCB by Cibacron blue and immunoaffinity chromatography was homogeneous on SDS-PAGE and silver stain. Porcine granulosa cells from ovarian small follicles were cultured (25,000/cm2) for 2 days in medium (Ham's F-12:DMEM, 1:1) + 5% fetal calf serum (FCS) to facilitate attachment, followed by 6 days in medium containing: FCS, hCB or h amniotic fluid (1-20%)+/- EGF (10 ng/ml); or 0.25% plasma-derived serum (PDS) containing human low density lipoprotein (LDL, 25 ug/ml), +/- AFP (0.05-5 ug), and +/- EGF and IGF-I (10 ng/ml). In this system, single growth factors do not stimulate proliferation, a characteristic also exhibited by AFP. When combined with EGF, however, AFP dose-dependently increased proliferation to levels equal to that obtained with 10% FCS (2.3-fold increase vs PDS/LDL controls). When combined with EGF+IGF-I, AFP again dose-dependently increased proliferation to levels equal to that obtained with 10% FCS+EGF (6.7-fold increase vs controls). Purified human albumin used in place of AFP was not effective. TGF-a but not PDGF could replace the proliferative activity of EGF. These results suggest that AFP at physiological levels, although not itself mitogenic, can enhance the mitogenic activity of EGF and TGF-a and may function to modulate growth factor-mediated proliferation during development and neoplasia.
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PMID:Human alpha fetoprotein enhances epidermal growth factor proliferative activity upon porcine granulosa cells in monolayer culture. 168 14

A family of 85/86-kDa (85K/86K) polypeptides closely linked to phosphatidylinositol kinase activity is found in polyoma middle-sized tumor antigen (MTAg)/pp60c-src complexes. MTAg and the 85-kDa phosphoprotein (pp85) could be reassociated in solution, or on blots, after denaturation with SDS. Results from such experiments focus attention on phosphorylation in controlling intracellular sorting and activation of pp85. Tyrosine phosphorylation seems important for recruitment of pp85 from cytosol to membrane. By blotting, pp85 is substantially cytosolic, whereas that recognized by anti-phosphotyrosine antibody is almost exclusively in membranes. Tyrosine phosphorylation also determined association of pp85 with MTAg. Manipulation of MTAg tyrosine phosphorylation, for example, by expressing MTAg using baculovirus vectors in the absence or presence of pp60c-src, dramatically affects reassociation. Finally, tyrosine phosphorylation appears to be involved in release of pp85 from MTAg, since vanadate increased its rate of dissociation.
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PMID:Tyrosine phosphorylation is a signal for the trafficking of pp85, an 85-kDa phosphorylated polypeptide associated with phosphatidylinositol kinase activity. 169 71

A transplantable murine breast tumor antigen (called JC tumor) has been recognized by the detection of McAb F36/22 with the method of immunoblotting. JC tumor antigen was isolated by Sepharose-CL-4B, then was purified by McAb F36/22 affinity chromatography. Solid phase RIA detection demonstrated that the specific activity of the antigen which was purified by 188.4 times was 148,000 cpm/mg protein. SDS-PAGE and immunoblot analysis revealed that the tumor antigen possessed a molecular weight of 60kd. Competitive binding RIA indicated that JC tumor antigen inhibited the combining of ductal carcinoma antigen with McAb F36/22. It implied that some groups (antigen determinant) on JC tumor antigen were the same as or similar to those on ductal cancer antigen.
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PMID:[Isolation and detection of murine transplantable breast tumor antigen by McAb F36/22]. 169 14

AFP is a major serum protein during ontogeny and is synthesized mainly by the mammalian fetal liver and yolk sac. Its synthesis ceases early in postnatal life and its reappearance in the serum in adult is a sign of hepatoma or yolk sac tumor, since these tumors produce AFP. This paper describes the cloning of rat AFP cDNA spanning complete coding region, its expression in E. coli and characterization of this recombinant AFP. The determination of the nucleotide sequence and cell-free translation of purified AFPmRNA suggested that rat AFP was synthesized as a precursor with a signal peptide of 24 amino acids followed by mature AFP of 587 amino acids. An expression vector was constructed with the cDNA and the introduction of the plasmid into E. coli resulted in the production of immunologically reactive AFP with a molecular weight of 65,000. The recombinant AFP was highly purified by immunoaffinity chromatography followed by SDS-PAGE. Analysis of the amino acids sequence indicated that the product was AFP lacking N-terminal 53 amino acid residues of preAFP.
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PMID:[Cloning and expression of rat alpha-fetoprotein cDNA in Escherichia coli]. 169 59

Insulin-like growth factor-I (IGF-I) is considered an important local mitogenic growth factor involved in autocrine/paracrine regulation of human breast cancer cell proliferation. We have characterized the IGF-I-like activity and studied its hormonal regulation by estradiol in the MCF-7 human breast cancer cell line. We found that the radioimmunoassayable IGF-I-like activity measured in conditioned medium (CM) is predominantly due to the presence of IGF-binding proteins (IGFBP). Acid chromatography demonstrated that most of the IGF-I-like activity eluted in the high molecular weight fractions and less than 10% co-eluted with authentic IGF-I (mol wt 7500). Binding protein activity measured by a 125I-IGF-I-ligand binding IGFBP-assay was present in these same high molecular weight fractions. SDS-polyacrylamide gel electrophoresis and 125I-IGF-I-ligand blot analysis of the CM showed the presence of two species of binding proteins of 29 kDa and 41 kDa molecular weight which demonstrated specific 125I-IGF-I binding activity. Estradiol did not stimulate IGFBP activity as assessed by the IGFBP-assay and as indirectly reflected by the IGF-I-like activity in the high molecular weight fractions. We conclude that the IGF-I-like activity in CM from human breast cancer cell cultures is predominantly due to the presence of IGFBP. Binding proteins of apparent molecular weight 29 kDa and 41 kDa are present in CM from MCF-7 cells. Assessment of their hormonal regulation showed that estradiol did not stimulate IGFBP. However, this needs to be assessed more stringently using better quantitative estimations for BP. The IGF-binding proteins may have an important role in the regulation of tumor cell growth by influencing the local concentrations and receptor mediated actions of IGF-I.
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PMID:Characterization and hormonal regulation of radioimmunoassayable IGF-I (insulin-like growth factor I) like activity and IGF-binding proteins secreted by human breast cancer cells. 170 Jun 62

The physico-chemical nature of Marek's disease tumor-associated surface antigen (MATSA) on Marek's disease (MD) lymphoblastoid tumor cell line (MDCC-MSB1-clo.18) was examined by the cellular enzyme-linked immunosorbent assay (CELISA) and the sandwich enzyme-linked immunosorbent assay (ELISA) using an anti-MATSA immune serum or a monoclonal antibody (MAb) 2B9 developed against MATSA. Our results indicate that MATSA is a glycoprotein and 2B9 recognizes an antigenic site in the protein moiety of MATSA. MATSA was solubilized from MSB1-clo.18 cells by treatment with 0.5% Nonidet P-40, and purified by affinity chromatography coupling with 2B9 and further by ion exchange chromatography on diethylaminoethylcellulose (IECD). MATSA was eluted with 0.2 to 0.3 M KCl in IECD and the purity of MATSA was increased about 2,500-fold. The purified MATSA was shown to have a molecular weight (Mr) of 70,000 by SDS-PAGE. The reactivity of purified MATSA with anti-thymus cell serum was examined. MATSA was detectable by anti-thymus cell serum, although 2B9, which was used to purify MATSA from MSB1-clo.18 cells, was not reactive to cells prepared from the thymus. However, MATSA was no longer detectable after the absorption of anti-thymus cell serum by chicken bursa cells. The absorption of anti-thymus cell serum by chicken red blood cells (RBC) had no effect on the reactivity against MATSA. These results suggest that MATSA may be a lymphocyte-specific antigen modified during leukemogenesis by Marek's disease virus (MDV).
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PMID:Analysis of Marek's disease tumor-associated surface antigen on MDCC-MSB1-clo.18 cells. 170 27


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