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)

Proteases capable of activating procollagenase from gingiva and from fibroblast and macrophage monolayer cultures were harvested from homogenates of canine tumor mast cells. The mast cell proteases lysed casein and Azocoll but not native collagen. In low salt concentrations the enzymes existed at high molecular weight complexes, which were dissociated by increasing the salt concentration above 1.0 M (NaCl, KCl). Gel filtration in 1.4 M KCl separated the protease activity into three peaks, all of which activated procollagenase. Two of the enzymes showed substrate specificities (hydrolysis of p-tosyl-L-arginine methyl ester and benzoyl-tyrosine ethyl ester) and reactive center reactivities similar to pancreatic trypsin and chymotrypsin. Based on gel filtration, apparent molecular weights of 160 000 (p-tosyl-L-arginine methyl ester esterase), 90 000 (main procollagenase activator) and 36 000 benzoyl-tyrosine ethyl ester esterase) were determined. Activation of procollagenase resulted in a 18-20 000 decrease of the molecular weight. The activation was directly related to the amount of activator added within certain limits. Further addition of activator resulted in proteolytic inactivation of collagenase.
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PMID:Activation of fibroblast procollagenase by mast cell proteases. 5 9

Ovarian carcinoma contains an antigen (TA) which is stable at 100 degrees. Rabbit antisera to glycoprotein-rich extracts of tumors detect TA in 70 per cent of ovarian malignancies, in some benign ovarian cysts, certain normal lung preparations, normal cervix, and squamous-cell carcinoma of the cervix. Highest levels may be associated with mucin secretion. No detectible antigen was present in normal ovary, plasma, A, B, and O erythrocytes, leukocytes, placenta, brain, heart, liver, corpus uteri, spleen, skeletal muscle, or kidney. Prolonged digestion of boiled tumor extracts with papain, trypsin, chymotrypsin, on Sephadex G-150 corresponding to a globular protein of 27,000 to 36,000 molecular weight. A beta-globulin mobility is seen in immunoelectrophoresis. It appears that TA differs in tissue specificity and molecular size from other known ovarian cancer associated antigens.
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PMID:A thermostable antigen associated with ovarian cancer. 6 15

A 32,000-dalton protein (p32) located in avian retrovirus cores was immunoprecipitated from [35S]methionine-labeled avian myeloblastosis virus (AMV) propagated in cultured chicken embryo fibroblast cells by an antiserum preparation (sarc III) derived from tumor-bearing hamsters injected with cloned and passaged cells from an avian sarcoma virus-induced primary hamster tumor. Since sarc III serum apparently contained antibodies only to virus-coded proteins and not to chicken cellular proteins, the immunoprecipitation of p32 from AMV by sarc III serum strongly suggested that p32 is virus coded. The origin of p32 was more definitively established by demonstrating the existence of a structural relationship between p32 and the AMV DNA polymerase. AMV p32 cross-reacted with the beta polypeptide of AMV alphabeta DNA polymerase in radioimmunoprecipitation and radioimmunoprecipitation inhibition assays, indicating that p32 and beta share common antigenic determinants. This relationship was clarified by sodium do-decyl sulfate-polyacrylamide gel electrophoretic analysis of the peptides generated by limited proteolysis of 125I-labeled AMV DNA polymerase polypeptides and of 125I-labeled AMV p32 by chymotrypsin or Staphylococcus aureus V-8 protease. The peptides which appeared during proteolytic digestion of p32 were a subset of those produced by digestion of the beta polypeptide; however, p32 had no discernible peptides in common with the alpha polypeptide. Further, all of the peptides produced by limited proteolysis of beta were present in the digests of either p32 or alpha. Our findings suggest that p32 is apparently derived by cleavage of the beta polypeptide of AMV DNA polymerase, presumably at a site near or identical to that at which alpha is generated from beta by proteolytic cleavage.
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PMID:Virus-coded origin of a 32,000-dalton protein from avian retrovirus cores: structural relatedness of p32 and the beta polypeptide of the avian retrovirus DNA polymerase. 8 16

The tyrosinase activity in two sucrose gradient isolated melanosome fractions from a melanotic hamster melanoma was found to increase after alpha-chymotrypsin treatment. The enhancement in tyrosinase activity had its maximum at a concentration of 1 mg/ml alpha-chymotrypsin after 120 min incubation at 37 degrees C. No direct activating effect of alpha-chymotrypsin was found either on the soluble tyrosinase fraction from freshly prepared untreaed whole-tumor homogenate or on purified mushroom tyrosinase. The activating effect of alpha-chymotrypsin upon the melanosome tyrosinase is believed to be due to the endopeptidic hydrolysis of the--CO--NH--bound existing between tyrosinase and tyrosine and phenylalanine residues in the melanin molecule. Although alternative interpretations are not excluded, the observed enhancement in tyrosinase activity after alpha-chymotrypsin treatment of melanosomes might indicate the existence of an "enzyme liberating" mechanism in the melanosomes.
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PMID:Chymotrypsin activation of melanosome tyrosinase in hamster melanotic melanoma. 11 73

Mechanical and enzymatic methods of disaggregating tumors were studied with the goals of (1) minimizing cell losses while (2) maintaining functional and surface membrane markers needed to objectively identify inflammatory cells (IC)1 in resultant suspensions. Application of the principles and methods described makes accurate estimation of the percentage of each IC type present in neoplasms possible for the first time. Compared to purely mechanical means of disaggregating tumors, all enzyme mixtures tested markedly increased yields of viable cells/g neoplasm. Best results were obtained with a combination of collagenase and a protease of broader substrate range (alpha chymotrypsin, papain, pronase or trypsin). The combination of enzymes that gave the highest yields with the least effect on inflammatory cell markers was trypsin, collagenase and DNAse (TCD). Because mechanical injury appeared to be the greatest single cause of cell loss (the enzymes themselves had little direct effect), potential sources were identified and either eliminated or minimized. With TCD, depending on the tumor system, cell recovery (measured as DNA recovered in cell suspensions) was as high as 50% and yields were as much as 6.9 X 10(8) viable cells/g tumor. Complete disaggregation was not required to obtain representative IC populations from tumor fragments. Neutrophils, eosinophils and mast cells from disaggregated neoplasms were counted in Giemsa stained cytocentrifuge preparations based on their unique morphologic appearances. Macrophages were identified by their capacity to phagocytose zymosan, a function which proved highly resistant to the effect of enzymes. Flourescent microscopic identification of brain associated thymus antigen (BATA) allowed quantification of T lymphocytes, since this marker was virtually unchanged by enzyme exposure. Surface immunoglobulin (Ig) was stripped from B lymphocytes most rapidly by pronase and chymotrypsin, slowly by trypsin and papain, and not at all by collagenase. Ig positive cells therefore could be quantified in suspensions generated by collagenase or very short (20 min) exposure of fragments to trypsin.
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PMID:Inflammatory cells in solid murine neoplasms. I. Tumor disaggregation and identification of constituent inflammatory cells. 18 47

The tumor promoter phorbol myristate acetate (PMA) induces the production of the serine protease plasminogen activator (PA) in cultures of normal chick embryo fibroblasts (CEF) and synergistically enhances PA production in Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF). Following PMA treatment of serum-free RSVCEF cultures, PA induction is accompanied by distinct morphological changes, including enhanced cell clustering and the formation of dense cellular aggregates. These alterations in the morphology of the PMA-treated transformed cells are inhibited by several protease inhibitors, including leupeptin, NPGB, SBTI, benzamidine and DFP, the specific inhibitor of serine enzymes. A number of protease inhibitors are ineffective in preventing the PMA-induced morphological changes; these include inhibitors of trypsin, chymotrypsin, elastase, thrombin and, most importantly, plasmin. The use of a fluorescent substrate to assay PA directly demonstrated that the pattern of inhibiton of PA activity correlates exactly with the inhibition of morphological changes. The of 3H-DFP to label and characterize serine zymes in the culture fluid from PMA-treated cells further indicated that PA is the serine protease responsible for the morphological changes. Thus PA itself can catalytically alter cellular behavior in culture independent of plasminogen, until not its only known natural substrate.
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PMID:Phorbol ester-induced morphological changes in transformed chick fibroblasts: evidence for direct catalytic involvement of plasminogen activator. 22 74

Lymphocyte-activating factor (LAF) has been shown to be produced by LPS-stimulated human adherent cells (monocytes) and peripheral leukocytes, but many non-macrophage cell lines failed to produce LAF. Other macrophage activators including latex microspheres, antigen-antibody complexes, and barium sulfate induce the production of LAF. There is a delay of 6 hr before significant amounts of LAF activity appear in the supernatant medium and maximum activity is found after 12 to 24 hr. Chromatography of concentrated crude supernatant fractions containing LAF activity on Sephadex G-100 gave two peaks of activity (approximately 85,000 and 13,000 daltons). The latter constitutes the major activity and has been purified at least 500-fold with Sephadex G-100, anion exchange, and adsorption chromatography. Optimal stimulation with LAF induces mitosis in 10% of murine thymocytes. The purified activity is sensitive to chymotrypsin and is not affected by treatment with sodium periodate, sulfhydryl reagents, and phenylmethanesulfonylfluoride. The response of thymocytes to LAF decreases with age after 10 weeks and thymocytes obtained from animals injected with cortisone or tumor-bearing animals have an increased responsiveness to LAF.
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PMID:Purification and properties of human lymphocyte activating factor (LAF). 30 Jul 51

The physicochemical properties of nuclear and cytosolic glucocorticoid-binding components from corticoid-sensitive (CS) and corticoid-resistant (CR) mouse lymphoma P1798 cells have been compared. Nuclei or cytosol fractions were prepared from lymphocytes that had been labeled at 37 or 4 degrees, respectively, with 30 nM [3H]triamcinolone acetonide ([3H]TA). [3H]TA was extracted with 0.6 M KCl, 10 mM spermidine, or 4.5 mM MgCl2 from CS nuclei and with 0.6 M KCl or 10 mM spermidine from CR nuclei. As reported previously, nuclear-associated [3H]TA in CR cells was resistant to extraction with mM concentrations of MgCl2. Loss of bound steroid during extraction with 0.6 M KCl was minimized by including the chymotrypsin inhibitor, carbobenzoxy-L-phenylalanine, in the extraction buffer. The inhibitor was not required during extraction with spermidine or MgCl2. Nuclear and cytosolic extracts were examined by analytical agarose gel filtration and glycerol density gradient centrifugation under high salt (0.6 M KCl) conditions. The glucocorticoid-binding component in KCl, spermidine, and MgCl2 extracts from CS nuclei was considerably larger and more asymmetrical [Stokes radius, 57 to 59 A; sedimentation coefficient, 3.64 to 3.70S; molecular weight, 90,000 daltons; frictional ratio, 1.8; axial ratio (prolate ellipsoid), 15] than the [3H]TA-macromolecular complex in KCl and spermidine extracts from CR nuclei[Stokes radius, 29 A; sedimentation coefficient, 3.23 to 3.30S; molecular weight, 40,000 daltons; frictional ratio, 1.25; axial ratio (prolate ellipsoid), 5]. Control experiments showed that the smaller size of the glucocorticoid-binding component in CR nuclei was probably not due to cleavage of a larger, CS-like complex during the extraction procedure. The larger size of the CS [3H]TA complex did not appear to result from aggregation of s a smaller species. No difference in physicochemical parameters of the binding component was observed if cells were labeled with [3H]dexamethasone instead of [3H]TA. However, [3H]dexamethasone complexes were less stable than those formed with [3H]TA as indicated by considerable dissociation of [3H]dexamethasone during gel filtration and gradient centrifugation. This may be due to the 3- to 5-fold lower relative binding affinity of [3H]dexamethasone. Analysis of [3H]TA-labeled cytosol by gel filtration and gradient centrifugation revealed the presence of a single binding component with physicochemical properties similar to those of nuclear [3H]TA complexes from the same strain of tumor. These results suggest that previously described differences in extractability of nuclear-associated [3H]TA between the CS and CR strains of mouse lymphoma P1798 and the lack of response of CR P1798 to glucocorticoid administration may be due, at least in part, to the presence of an altered glucocorticoid-binding component in the resistant tumor cells.
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PMID:Physicochemical differences between glucocorticoid-binding components from the corticoid-sensitive and -resistant strains of mouse lymphoma P1798. 47 39

Glutamate dehydrogenase is very susceptible to carbamylation which results in loss of activity. The effect of a number of proteolytic enzymes (pronase, trypsin and chymotrypsin) on native and carbamylated glutamate dehydrogenase was tested. In all cases, the carbamylated enzyme was at least twice as susceptible to proteolysis as the native enzyme. Antibodies were prepared against glutamate dehydrogenase and carbamylated glutamate dehydrogenase; the carbamylated enzyme was antigenically indistinguishable from the native enzyme. Preliminary experiments indicate that the carbamylated glutamate dehydrogenase is taken up by ascites tumor cells while glutamate dehydrogenase is not. It seems possible that the effects described can be extrapolated to degradation by lysosomes and to other covalently modified enzymes.
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PMID:Increased susceptibility of carbamylated glutamate dehydrogenase to proteolysis. 61 12

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


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