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 relation between the lifetimes of the triplet states of various porphyrins and their photosensitizing effects on the photodynamic therapy (PDT) of tumor has been examined. Diethylene-triamine pentaacetic acid ester of 4-[1-(2-hydroxy-ethyloxy)ethyl]-2-vinyl deuteroporphyrin-IX gallium (III) complex (Ga-DP), zinc (II) complex (Zn-DP), and manganese (III) complex (Mn-DP) and Photofrin II (PII) are used as the photosensitizer. The triplet lifetimes have been measured for the samples adsorbed on filter paper (FP) and found to be 57 ms (Ga-DP), 26 ms (Zn-DP), less than or equal to 10 microseconds (Mn-DP) and 9 ms (PII). The phosphorescence of Ga-DP in tumor-bearing golden hamsters are measured both in tumor tissue and in liver. They show bi-exponential decay with the lifetimes of about 5 and 20 ms. From the values, the generation rate, kct[3O2], of singlet molecular oxygen in living animal tissue may be estimated to be an order of 10(2) s-1. The PDT effects have been quantitatively investigated for in vitro experiments; upon irradiation the growth inhibitions of mouse p388 leukemia cells are obtained as a function of concentration of Ga-DP, Zn-DP, Mn-DP and PII. The experimental results indicate that the PDT effects depend essentially on the triplet lifetimes of the photosensitizers.
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PMID:Critical importance of the triplet lifetime of photosensitizer in photodynamic therapy of tumor. 278 Aug 23

The properties of the adenylate cyclase from forskolin-resistant mutants of Y1 adrenocortical tumor cells was compared with the properties of the enzyme from parental Y1 cells in order to localize the site of mutation. In parental Y1 cells, forskolin stimulated adenylate cyclase activity with kinetics suggestive of an interaction at two sites; in mutant cells, forskolin resistance was characterized by a decrease in enzymatic activity at both sites. Forskolin potentiated the enzyme's responses to NaF and guanyl-5'-yl imidodiphosphate (Gpp(NH)p) in parent and mutant clones, and the mutant enzyme showed the same requirements for Mg2+ and Mn2+ as did the parent enzyme. The adenylate cyclase associated with forskolin-resistant mutants was insensitive to ACTH and was less responsive to Gpp(NH)p than was the parent enzyme. In parental Y1 cells and in the forskolin-resistant mutants, cholera toxin catalyzed the transfer of [32P]ADP-ribose from [32P]NAD+ into three membrane proteins associated with the alpha subunit of Gs; however, the amount of labeled ADP-ribose incorporated into mutant membranes was reduced by as much as 70%. Both parent and mutant membranes were labeled by pertussis toxin to the same extent. The insensitivity of the mutant adenylate cyclase to ACTH and Gpp(NH)p and the selective resistance of the mutant membranes to cholera toxin-catalyzed ADP-ribosylation suggest that a specific defect associated with Gs is involved in the mutation to forskolin resistance in Y1 cells.
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PMID:Forskolin-resistant Y1 mutants harbor defects associated with the guanyl nucleotide-binding regulatory protein, Gs. 282 64

A lymphoid cell line CK-a was established from peripheral blood of an infant with acute lymphoblastic leukemia of non-T, non-B cell type with mediastinal tumor. The CK-a cells were positive for surface immunoglobulins, Epstein-Barr virus-specific nuclear antigen, HLA-DR and Leu 12 antigens, and negative for sheep erythrocyte-rosette-receptor, and Leu 1, 2, 3 and 4 antigens. Budding particles were detected in electron micrographs of ultrathin sections of the CK-a cells. In the culture media of CK-a cells, particles with a buoyant density of 1.16 g/ml and labeled with [3H]uridine and [35S]methionine but not with [3H]thymidine were found to carry reverse transcriptase activity which preferred Mg2+ to Mn2+. Enveloped particles of 80 to 120 nm in diameter were detected in the fractions at 1.16 g/ml by electron microscopy. Thus, the particles had properties compatible with a definition of Retroviridae, and were tentatively named CK virus (CKV). The genome size of CKV RNA determined by agarose-acrylamide composite gel electrophoresis was 6.1 +/- 0.2 kb. Immune electroblotting assay detected antibody reactive with a CKV protein with a molecular weight of 67,000 in the serum of the patient, but not in sera of an adult T cell leukemia patient and healthy controls. No syncytia were formed by mixed cultures of CK-a and XC cells.
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PMID:Retrovirus produced by a lymphoid cell line from an infant with acute lymphoblastic leukemia. 288 14

The toxicity and selectivity of 3,4-dihydroxybenzylamine (DHBA), an experimental antimelanoma agent that cannot enter the melanin pathway, broadly paralleled that of L-dopa in a panel of human melanoma cell lines sensitive or resistant to the latter drug. A human retinoblastoma cell line was found to be sensitive to both compounds. The toxicity and selectivity of both catechols were associated with inhibition of DNA synthesis; DHBA was more potent yet allowed a much greater degree of recovery compared with an equitoxic level of dopa. Dopa and DHBA had similar, dose-dependent effects on the cell cycle, arresting cells in S phase at low doses and in G1 at high doses. Replication of the DNA virus adenovirus was found to be inhibited by both agents. There was no difference between sensitive and resistant cell lines in the manganese or copper/zinc forms of superoxide dismutase, or in iron content and iron-binding capacity. Catechol toxicity was inhibited by the hydrogen peroxide scavenging agents pyruvate and methaemoglobin. Sensitivity to catechols did not correlate with melanin or tyrosinase content, rate of incorporation of tyrosine or dopa, intracellular levels of phenylalanine or tyrosine, or binding of a new monoclonal antibody directed against a melanosomal protein. These results indicate that DHBA and dopa exhibit selective toxicity for neural crest tumor cells independently of the melanisation pathway and of the superoxide scavenging system.
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PMID:Melanin synthesis and the action of L-dopa and 3,4-dihydroxybenzylamine in human melanoma cells. 290 84

A protein tyrosine kinase that phosphorylates both alpha and beta subunits of inactivated (Na+,K+)-ATPase from dog kidney was purified about 500-fold from Ehrlich ascites tumor cell membranes. The enzyme required divalent cations Mn2+, Mg2+, or Fe2+ but was inhibited by Cu2+ or Zn2+. The purified enzyme phosphorylated the beta subunit about five times faster than the alpha subunit of the (Na+,K+)-ATPase. The random polymer poly(Glu80Tyr20) was an excellent substrate while casein was only marginally phosphorylated. In contrast, the purified transforming gene product of Rous sarcoma virus phosphorylated all three substrates and the (Na+,K+)-ATPase was preferentially phosphorylated on the alpha subunit. The transforming gene product of Fujinami sarcoma visue and EGF receptor kinase from A431 cells phosphorylated (Na+,K+)-ATPase poorly whereas casein was an excellent substrate. The molecular weight of the partially purified protein tyrosine kinase from Ehrlich ascites tumor cells determined by gel filtration was about 60,000. One of two major phosphorylated phosphopeptides resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis had an Mr of 60 kDa, thus suggesting that it might be the autophosphorylated protein tyrosine kinase. A phosphatase that hydrolyzes phosphorylated histones or poly(Glu80Tyr20) was partially purified from the same membrane.
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PMID:A tyrosine-specific protein kinase from Ehrlich ascites tumor cells. 302 71

A UDP-Gal:N-acetyllactosaminide alpha (1,3)-galactosyltransferase from Ehrlich ascites tumor cells has been purified over 200,000-fold to apparent electrophoretic homogeneity. The purified enzyme transfers D-galactosyl groups from UDP-Gal to beta-D-Gal-(1,4)-D-GlcNAc in alpha-linkage. The apparent Km values for donor and acceptor substrates are 12.6 microM and 1.15 mM, respectively. The trisaccharides beta-D-Gal(1,4)-beta-D-GlcNAc(1,2)- or (1,6)-D-Man exhibit a Km 5-fold lower than that of N-acetyllactosamine, and an even more pronounced effect is observed with the biantennary pentasaccharide beta-D-Gal(1,4)-beta-D-GlcNAc(1,2)-[beta-D-Gal(1, 4)-beta-D-GlcNAc-(1,6)]-D-Man (Km 0.10 mM). The transferase shows a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions with an apparent subunit molecular weight of 80,000, exhibits a pH optimum at 6.2, and requires Mn2+ ions and detergent for enzymatic activity. Specificity studies using immobilized oligosaccharides show that the minimum acceptor structure for the alpha-galactosyltransferase is N-acetyllactosamine. The narrow specificity of the alpha-galactosyltransferase is indicated by the fact that lactose, beta-D-Gal(1,3)-D-GlcNAc, and beta-D-Gal(1,4)-[alpha-L-Fuc(1,3)]-D-GlcNAc are very poor acceptors. The enzyme differs from the blood-group B-specified galactosyltransferase in that the sequence alpha-L-Fuc(1,2)-beta-D-Gal(1,4)-D-GlcNAc is not an acceptor. Oligosaccharides, glycoproteins, glycolipids, and glycosaminoglycans containing the terminal nonreducing N-acetyllactosamine unit all serve as acceptors for the enzyme.
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PMID:Purification and characterization of a UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase from Ehrlich ascites tumor cells. 308 77

The ability of Co2+ to substitute for Mn2+ in exogenous and endogenous galactosyltransferase reactions was tested. Exogenous transfer was measured towards different high and low molecular weight galactose acceptors using galactosyltransferase from the following sources: crude serum, the serum enzyme partially purified by affinity chromatography and a pure enzyme preparation from milk. Endogenous transfer was estimated in preparations from human urinary bladder tumor cells and from rat liver microsomal fractions. The results show that Co2+ is able to substitute for Mn2+ in some exogenous and endogenous galactosyltransferase reactions. This ability seems to depend on the molecular structure of the galactose acceptor as well as on the nature of the enzyme.
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PMID:Co2+ is able to substitute for Mn2+ in some exogenous and endogenous galactosyltransferase reactions. 313 94

Tyrosine protein kinase activity has been detected in the mitochondrial fraction purified from sarcoma 180 tumor cells. Following hypotonic disruption of mitochondria, tyrosine kinase activity appeared to cosediment with monamine oxidase, marker enzyme of mitochondrial outer membrane; meanwhile, serine and threonine kinases were found to be associated with the inner membrane and matrix of mitochondria. Mitochondrial tyrosine kinase(s) showed thermosensitivity and Mn2+ dependence, useful properties for its characterization and separation from tyrosine kinases associated with other particulate fraction and from serine and threonine kinases associated with mitochondria. Following in vitro incubation of mitochondria with labelled ATP as substrate and analysis by PAGE, a complex pattern of phosphotyrosine containing proteins with a major band of 50-55 kilodaltons resulted.
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PMID:Identification and characterization of tyrosine kinase activity associated with mitochondrial outer membrane in sarcoma 180 cells. 334 88

In accordance with earlier work the manganese (III) derivative of meso-tetra(4-sulfonatophenyl)porphine (TPPS4) is found to accumulate in the tumors of L1210-bearing mice. The tumor/liver ratio of porphyrin extends from 1.5 to 3.6 over a range of dose and time periods. The subcellular distribution of porphyrin in L1210 tumor and liver, and the tissue distribution (cellular, stroma, soluble) in L1210 tumor indicates that the porphyrin tends to be located predominantly in soluble and stromal fractions. These data are interpreted in terms of the physiology and composition of neoplastic tissue to formalize a mechanism for the localization of Mn(III)TPPS4 in L1210 tumor and a general working hypothesis for the localization of porphyrins in neoplastic tissue. The in vivo stability of Mn(III)TPPS4 is also addressed and is found to be demetallated to a degree of approximately 1% in liver and kidney.
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PMID:Mechanism of the localization of manganese (III) mesotetra(4-sulfonatophenyl)porphine in mice bearing L1210 tumors. 337 Jun 27

Paramagnetic metalloporphyrins were examined for their in vivo bio-distribution and their ability to enhance nuclear magnetic resonance imaging of human tumor xenografts in nude mice. The metalloporphyrins tested were: manganese tetrasodium-meso-tetra(4-sulfonatophenyl)-porphine (MnTPPS); manganese meso-tetra-4-pyridylporphine; and gadolinium meso-tetra-4-pyridylporphine. All exhibited high molar relaxivities in aqueous solution. In vivo, at a dose of 2 mg/mouse, MnTPPS depressed the longitudinal relaxation time, T1, significantly in the kidney and less in lung and blood. Manganese meso-tetra-4-pyridylporphine depressed T1 in the kidney, lung and liver, while gadolinium meso-tetra-4-pyridylporphine caused large T1 depressions in the blood, liver, brain and tumor, probably due to dissociation of the metalloporphyrin and binding of Gd to plasma or tissue proteins. At a dose of 10 mg/mouse, MnTPPS caused marked T1 depressions of all tissues tested within 5 min of inoculation, but 48-72 h later, T1 values of normal tissues had returned to near normal, while those of the tumors remained significantly depressed. MnTPPS was able to significantly enhance the intensity of nuclear magnetic resonance images of MX-1 and ZR-75 human breast tumors and CX-1 and LS174T human colon tumor xenografts in nude mice. The results demonstrate that paramagnetic metalloporphyrins, because of their high relaxivities and retention in tumors, have the potential for use as tumor-selective contrast agents for nuclear magnetic resonance imaging.
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PMID:Metalloporphyrin enhancement of magnetic resonance imaging of human tumor xenografts in nude mice. 339 12


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