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)

Cell lines were successfully established in continuous suspension culture from 10 patients with a histopathological diagnosis of diffuse histiocytic lymphoma (SU-DHL-1 to SU-DHL-10), two with North American Burkitt's lymphoma (SU-AmB-1 and SU-AmB-2), and one with acute lymphoblastic leukemia (SU-ALL-1). By screening a variety of parameters, including media, sera, effusion fluids, feeder layers, and chemical supplements, the nutritive growth requirements of lymphoma cells obtained from malignant effusions and lymph node biopsies were determined for each tumor. Most of these cell lines initially required human skin fibroblast or epithelial cell feeder layers from which they could be weaned after one to six weeks in culture and maintained in Roswell Park Memorial Institute Tissue Culture Medium 1640 containing 20% fetal calf serum and 10% pooled human serum. Several of these cell lines were successfully cloned on 0.5% Noble agar substrates. In the presence of human serum and selected feeder monolayers, cloning efficiencies increased significantly from less than 1% to 15 to 25%. In addition, the cloning efficiencies of certain cell lines showed a concentration-dependent increase with specific chemical supplements including L-cysteine and dithiothreitol. Placental colony-stimulating factor, nerve growth factor, epithelial growth factor, and fibroblastic growth factor were ineffective in augmenting the cloning efficiencies of the human lymphoma cell lines. After a single passage on agar, cells subpassaged from visible colonies showed markedly increased cloning efficiencies to levels as high as 50%. Such cloning efficiencies, coupled with the use of replica plating, make this technique applicable to genetic and quantitative radiobiological, immunological, and chemotherapeutic studies. Although these methods have thus far been used only with lymphoreticular tumors, they may also be applicable to the cell culture of other human neoplasms and normal tissues.
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PMID:Feeder layer and nutritional requirements for the establishment and cloning of human malignant lymphoma cell lines. 37 94

Macromomycin (MCR), a polypeptide antibiotic previously shown to have antitumor activity in experimental tumors, has been purified into an electrophoretically homogeneous component with an approximate molecular weight of 12,500. MCR has alanine as an NH2-terminal amino acid, 4 cysteine residues, and no arginine or methionine residues. With a fluorescence assay and agarose gel electrophoresis, MCR was shown to induce strand breaks in PM2 DNA in vitro. 2-Mercaptoethanol inhibited the DNA cleavage activity of MCR. When incubated with Novikoff hepatoma ascites cells in tissue culture, MCR caused Novikoff hepatoma ascites cell DNA degradation as observed by the slower sedimentation of DNA on alkaline sucrose density gradient centrifugation when compared to untreated cell DNA. DNA synthesis in Novikoff hepatoma ascites cells was inhibited by 80% after a two-hr treatment with MCR (0.03 microgram/ml). RNA and protein syntheses were inhibited by 25 and less than 10%, respectively, at this concentration of drug. At a concentration of MCR (1.0 microgram/ml), syntheses of DNA and RNA in Novikoff hepatoma ascites cells were totally inhibited. The results of this study suggest that MCR may inhibit tumor cell growth by causing DNA breakage with subsequent inhibition of DNA and other macromolecule syntheses.
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PMID:Purification and mechanism of action of macromomycin. 42 Dec 1

The L-cyst(e)ine requirements of normal and malignant cells are reviewed and expanded within the context of establishing whether the measurement of gamma-cystathionase levels constitutes a predictive test for tumor sensitivity to L-cyst(e)ine depletion. The ability of both purified L-cysteine desulfhydrase and gamma-cystathionase to inhibit the growth of the L-cystine-dependent L1210 leukemia in culture is presented, as well as approaches to circumvent the limitations of these enzymes for in vivo therapy. The ability of proparagylglycine to inhibit L-cysteine biosynthesis in vivo is reviewed for its possible use in combination therapy. In addition, the ability of poly D,L-alanine modification of Escherichia coli L-asparaginase to increase the plasma half-life in mice tenfold as well as to decrease the immunogenicity of the enzyme is presented.
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PMID:L-cyst(e)ine requirements of malignant cells and progress toward depletion therapy. 46 47

Tumor tissue of cutaneous fibrosarcoma was solubilized with salt, acetic acid and salt-extracted after pepsin treatment. Type III collagen was observed in neutral soluble collagen, 1.5 M and 2.4 M NaCl precipitated fractions after pepsin treatment. Type III collagen fraction precipitated with 1.5 M NaCl eluted in the alpha2 region when chromatographed on CM-cellulose without reduction, while the type III collagen partially purified with 1.5 M NaCl eluted between the position of alpha1(I) and beta12 after reduction and alkylation. Analysis of amino acid showed the presence of cysteine and the high content of hydroxyproline following CM-chromatography of 1.5 M NaCl precipitated type III collagen fraction. Acidic glycosaminoglycans were composed of hyaluronic acid, chondroitin sulfate, dermatan sulfate and heparan sulfate, and the first two were major components of fibrosarcoma.
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PMID:Biochemical characterization of connective tissue macromolecules derived from cutaneous fibrosarcoma. 59 35

Ehrlich ascites tumour cells contain a neutral protease, capable of solubilising fluorescein-labelled telopeptides from fluorescein-labelled polymeric collagen fibrils. The cells also contain an inhibitor for this enzyme and for trypsin. The enzymically inactive enzyme-inhibitor complex can be dissociated with the mercurial thiol agent, mersalyl, with the consequent regain of enzymic activity. The reactivated neutral protease and also trypsin can be inhibited by addition of thiols such as cysteine, mercaptoethanol and dithiothreitol. Trypsin can be protected from inactivation by the tumor inhibitor by addition of cystine or L-1-tosylamido-2-phenylethyl chloromethyl ketone(TosPheCH2Cl)-inactivated chymotrypsin. The evidence suggests that the inhibitor contains a reactive thiol group which exchanges with one or more significant disulphide bridges in trypsin and the neutral protease, resulting in enzyme-inhibitor complex formation and loss of activity. Similarly, thiols interact with these enzymes resulting in a corresponding loss of enzymic activity. The evidence obtained with Tos-PheCH2Cl-inactivated chymotrypsin, which reactivated previously inhibited trypsin and neutral protease, demonstrates that the active site of the enzyme is not involved in the interaction with the thiol of the inhibitor but that the significant disulphide bond in the enzyme is required for the maintenance of the active site conformation. This disulphide exchange mechanism is therefore a form of reversible allosteric control of proteolytic activity and has been shown to be distinct from the mechanism by which soya bean trypsin inhibitor interacts with trypsin.
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PMID:Evidence for the inhibition of trypsin by thiols. The mechanism of enzyme-inhibitor complex formation. 62 6

The preparation of a series of synthetic sulfur-containing amino acids is described. These compounds included heterocyclic analogues of L-cysteine, DL-norcysteine, and DL-homocysteine. The amino acids were assessed for their ability to inhibit the neutral amino acid transport systems of the Sarcoma 37 ascites tumor cell and their inhibitions were compared with those of L-methionine and L-ethionine. Transport studies indicated that the amino acids synthesized were capable of inhibiting the uptake of [3H]-L-histidine in the S37 cell.
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PMID:Synthetic sulfur-containing amino acids. Inhibition of transport systems in S37 ascites tumor cells. 72 14

Structural studies were carried out on a monotypic immunoglobulin (Ig) isolated from a patient suffering from a colon tumor. Results indicated that the light (L) chain of this protein belonged to the VkappaII subgroup and was devoid of known Inv allotypic determinants, whereas the heavy (H) chain variable (V) region belonged to the VHIII subgroup and its constant (C) region was of the gamma1 subclass and was Gm (a+Z+). The amino acid sequence of a total of 106 residues has been determined for this molecule. An extra cysteine was present at the fourth hypervarible region of the heavy chain. Preliminary results indicated that the Fc fragment of this protein did not include the inter-heavy-chain disulfide bonds.
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PMID:Chemical studies on a monoclonal immunoglobulin from a patient with carcinoma of the colon. 81 7

A pyrimidine nucleoside monophosphate kinase has been purified 2100-fold from rat liver. With ATP and dATP as phosphate donors the kinase uses CMP, dCMP, and UMP as phosphate acceptors. Ara-CMP is also phosphorylated by the kinase. In contrast to dCMP and UMP, CMP can be phosphorylated by dCTP. CTP and ara-CTP cannot substitute for dCTP. The stringent specificity of the phosphate donor site for ATP and dATP is lost when CMP serves as acceptor. All nucleoside triphosphates act as donors to a significant extent. No evidence has been found to suggest more than one enzyme. All activities, to different degrees, are strictly dependent upon preincubation at 37 degrees with a sulfhydryl reducing agent. Various reagents (85 mM) are ranked in order of increasing effectiveness of reactivation as follows: dithiothretiol greater than glutathione larger than or equal to 2-mercaptoethanol greater than L-cysteine greater than DL-alpha-lipoic acid. A NADP+-dependent thioredoxin (17 muM)-thioredoxin reductase system from Novikoff ascites rat tumor was found to be the most powerful reducing agent tested. CTP, dCTP, UTP, and dTTP (1 mM) do not affect the kinase activity regardless of the phosphate acceptor.
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PMID:A pyrimidine nucleoside monophosphate kinase from rat liver. 112 84

In a model system consisting of highly coupled rat liver mitochondria respiring in the presence of substrate, pyruvate kinase, phosphoenolpyruvate, ATP, hexokinase and glucose, the increase in the mitochondrial concentration results in a progressive decrease in the activity of pyruvate kinase. These results are in accord with a role of pyruvate kinase as a determinant of glycolytic activity by competing with mitochondrial oxidative phosphorylation for the available ADP. The addition of adequate amounts of the amino acids, cysteine, alanine and phenylalanine, known as inhibitors of pyruvate kinase, to living Ehrlich ascites tumor cell suspensions results in a stimulation of the respiratory rate and in a decrease of the glycolytic rate of the cells. Concomitant with these changes, there is an accumulation of intracellular phosphoenolpyruvate and ADP, and a decrease in pyruvate and ATP. These results provide additional evidence for paying attention to pyruvate kinase as another key enzyme whose properties and activities may be major determinants for the control of glycolysis and the Crabtree and Pasteur effects of tumor cells.
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PMID:Stimulation of tumor-cell respiration by inhibitors of pyruvate kinase. 117 5

The metastasis associated 72-kDa type IV collagenase is secreted as a latent proenzyme which is converted to an active 62-kDa form by autoproteolytic removal of an amino terminal profragment. The region immediately upstream from the cleavage site contains a highly conserved peptide sequence, MRKPRCGNPDV, which is present in all known members of the matrix metalloproteinase family. Evidence implicates the cysteine residue of this sequence as critical for maintenance of the latent form through coordination with the catalytic zinc atom of the active site. A synthetic peptide, TMRKPRCGNPDVAN (peptide 74), encompassing this conserved sequence, has been shown to inhibit the activated form of the 72-kDa type IV collagenase in vitro. In the present study we examine the ability of this peptide inhibitor to modulate tumor cell invasiveness. Peptide 74 and the control peptide 78, which contains a single substitution of serine for the "critical" cysteine residue, were added at 30 microM concentrations to the upper compartment of the Boyden chamber in the chemoinvasion assay using HT1080 and A2058 human tumor cells. In this assay a layer of reconstituted basement membrane, Matrigel, is coated onto chemotaxis filters and acts as a barrier to the migration of cells in the Boyden chambers. Only cells with invasive capacity can cross the Matrigel barrier. Peptide 74 containing the cysteine residue inhibited the invasion of both the HT1080 and A2058 cells through the Matrigel barrier; control peptide 78 was not inhibitory. Both peptides were shown to be without cytotoxic action and did not inhibit chemotaxis or affect cell number. This study demonstrates that addition of an excess peptide containing the matrix metalloproteinase prosegment inhibitory sequence can inhibit invasive activity at the cellular level and suggests that this may be a useful strategy to modulate tumor cell invasiveness in vivo.
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PMID:Inhibition of tumor cell invasion by a highly conserved peptide sequence from the matrix metalloproteinase enzyme prosegment. 131 44


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