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Disease
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:3.1.21.1 (
DNase
)
7,655
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cytosol from human benign hyperplastic and carcinomatous prostatic tissue has been shown to contain a progestin receptor with a dissociation constant of approximately 10(-9) M. The receptor was measured using 3H-labeled R 5020 (17 alpha, 21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. Progesterone, cyproterone acetate, and R 1881 (methyltrienolone) were efficient competitors to R 5020 for binding sites on the receptor whereas testosterone, 5 alpha--dihydrotestosterone, estradiol, cortisol, and several hydroxylated and saturated derivatives of progesterone did not compete. The [3H]R 2020-receptor-complex had a sedimentation coefficient of approximately 4 S, an isoelectric point of approximately 5, was heat-labile, and was destroyed by treatment with trypsin but not with
deoxyribonuclease
or ribonuclease. Seventeen of 21 patients with benign prostatic hyperplasia and three patients with prostatic carcinoma had 1 to 40 fmoles of specific R 5020-binding sites per mg of cytosol protein. One sample of normal prostatic tissue did not contain significant amounts of progesting receptor. Tissue specimens removed by transvesical adenoma enucleation displayed a larger number of specific R 5020-binding sites than electroresected specimens. The progestin receptor in hyperplastic prostate may be involved in the mechanism of the action of progestins used in the medical treatment of benign prostatic hyperplasia. Quantitation of progestin receptor in
cancer
of the prostate may form part of the basis of a predictive test program for endocrine therapy of prostatic
malignancy
.
...
PMID:Demonstration of a progestin receptor in human benign prostatic hyperplasia and prostatic carcinoma. 7 18
Low ionic strength (50 to 100 mM NaCl) and pH 6.0 were found to be optimal conditions for in vitro conversion of Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA)-negative nuclei to EBNA-positive nuclei by addition of the complement-fixing (CF) antigen extracted from Raji cells. In vitro conversion of nuclei to EBNA-positively was sensitive to
DNase
but not to RNase treatment. This suggests that nuclear DNA is a specific target substance to which EBV-CF antigen binds. If nuclei were fixed with methanol/acetic acid and subsequently treated with 0.6 M NaCl, EBNA could be eluted from in vitro-converted Ramos nuclei with 0.3 and 0.4 M NaCl. The same conditions were also found to be optimal for the adsorption and elution of EBV-CF antigen in DNA-cellulose chromatography. This indicates that the DNA-binding properties of EBNA antigen can be studied by "chromatography" on fixed nuclei followed by the ACIF test. The obvious advantages of this method over chromatography on DNA-cellulose are its simplicity, the possibility of testing many samples in one experiment and, especially, the use of minimal amounts of material. Significant differences in elution patterns for EBNA were found when nuclei derived from different cell lines (Ramos, Raji, and P3HR-1) were converted in vitro to EBNA-positivity. EBNA is eluted from in vitro-converted nuclei of EBV genome-positive P3HR-1 cells at an almost 0.1 M higher concentration of NaCl than is necesssary for a similar degree of elution from nuclei of EBV genome-negative Ramos cells.
Int J
Cancer
1978 Nov 15
PMID:Study of Epstein-Barr virus-determined nuclear antigen (EBNA) by chromatography on fixed cell nuclei. 8 40
A human lung tumor-associated fetal antigen (LTFA) has been partially isolated and characterized. The antigen that differs in several immunochemical parameters from previously described lung cancer antigens was shared by fetal lung and liver tissue. The neoantigen migrated in immunoelectrophoresis as an alpha2-beta globulin, had an average molecular size of 7S, and was soluble in 50% saturated ammonium sulfate. Whereas LTFA was insensitive to both
DNase
and RNase treatment, its antigenicity was completely abolished by pronase. The biologic significance of this antigen and its possible clinical use were discussed.
J Natl
Cancer
Inst 1979 May
PMID:Partial characterization of a fetal lung antigen associated with human bronchogenic carcinoma. 10 44
KCl extract from rat kidney, rat liver, and Morris hepatomas inhibited [3H]thymidine incorporation into cultured cells. Tissues came from male inbred BUF rats. The most pronounced inhibition was achieved with the kidney extract. Protein synthesis was not inhibited during a 24-hour exposure of the cells to the inhibitor. Incorporation of [3H]deoxycytidine was inhibited, as was cell growth, when the kidney KCl extract was present for several days. [3H]thymidine incorporation was inhibited almost immediately after the addition of the extract. The inhibition was reversible. Regular [3H]thymidine incorporation was restored 24 hours after removal of the inhibitor, which was neither arginase nor a thymidine-degrading enzyme. The inhibitor was stable to heat (80 degrees C for 10 min) and resistant to trypsin, pronase,
DNase
, and RNase. Exposure of the extract to proteolytic enzymes, hyaluronidase, and neuraminidase resulted in a loss of inhibitory activity only after extensive dialysis of the treated extract. The inhibitor appeared to be a mucoprotein in which the carbohydrate moiety may be responsible for the inhibition. The KCl extract also inhibited RNA synthesis and DNA synthesis by the de novo pathway. The inhibition of phosphorylation of thymidine, however, appeared to be the primary action of the inhibitor.
J Natl
Cancer
Inst 1979 Jun
PMID:Inhibition of tritiated thymidine incorporation in cultured cells by rat kidney extract. 15 53
DNA synthesis was studied in mouse ascites sarcoma cells using a permeable cell system. The sarcoma was induced by the Schmidt-Ruppin strain of Rous sarcoma virus. The cells were made permeable to nucleoside triphosphates by treatment with a hypotonic buffer containing 10 mM Tris Cl, 4 mM MgCl2, 1 mM EDTA, and 6 mM 2-mercaptoethanol (pH 8.0). DNA-synthetic activity in the permeable cells was highly dependent on four deoxyribonucleoside triphosphates, adenosine triphosphates, Mg2+, and a proper ionic environment. The activity was stimulated about 50% by the addition of an appropriate concentration of cytidine triphosphate, guanosine triphosphate, and uridine triphosphate in an assay mixture containing adenosine triphosphate and four deoxyribonucleoside triphosphates. DNA synthesis was confined to the nucleus and was sensitive to N-ethylmaleimide and
DNase
. The activity assayed by the permeable cell system correlated closely with the DNA-replicating activity assayed by [3H]deoxythymidine incorporation in intact cells. The close correlation between DNA synthesis in vitro and in vivo was further confirmed in cultured sarcoma cells synchronized with DNA synthesis. Analysis of the DNA synthesized in vitro by alkaline cesium sulfate density gradient centrifugation showed that over half the DNA synthesized in permeable cells was due to elongation of strands initiated in vivo. The permeable cell system appears to be a useful method for examining DNA replication of cells in suspensions.
Cancer
Res 1977 Jan
PMID:DNA synthesis inpermeable mouse ascites sarcoma cells. 18 30
Incubation of HeLa cells with the anticancer agent N-methyl-N-nitrosourea (MNU) results in: (a) depression of intracellular nicotinamide adenine dinucleotide levels; (b) stimulation of the chromatin-associated, chromosomal protein-modifying enzyme polyadenosine diphosphoribose [poly(ADP-ribose)] polymerase, which uses nicotinamide adenine dinucleotide as substrate; and (c) some fragmentation of cellular DNA.
DNase
treatment of HeLa nuclei in vitro also stimulates poly(ADP-ribose) polymerase activity, but not in nuclei derived from MNU-treated cells unless they have been subsequently incubated to allow for recovery from MNU damage. DNA polymerase activity is stimulated in vitro by poly(ADP) ribosylation of nuclear proteins. By using intact nuclei derived from MNU-treated HeLa cells, the repair via elongation of single-strand DNA breaks is demonstrated in vitro. This repair is dependent on DNA polymerase activity and is enhanced by adenosine diphosphate ribosylation of histones. Inhibition of poly(ADP-ribose) polymerase with nicotinamide results in extensive degradation of MNU-damaged DNA. Taken as a whole, these results suggest that poly(ADP-ribose) polymerase may play a role in the repair of alkylation damage to cellular DNA and that the inhibition of this enzyme in vivo might be exploited to potentiate the antitumor and carcinogenic activities of MNU.
Cancer
Res 1977 Sep
PMID:A putative role for nicotinamide adenine dinucleotide-promoted nuclear protein modification in the antitumor activity of N-methyl-N-nitrosourea. 19 15
The activities of enzymes catalyzing the formation of nucleic acid precursors, nucleoside kinases, as well as of those involved in the degradation of nucleic acids, were studied in nuclei of the liver of healthy persons, human hepatomas and the liver of patients with
cancer
of gastrointestinal tract. The activities of thymydine kinase and uridine kinase in the human hepatoma nuclear sap were found to increase 40- to 50-fold and 120- to 150-fold, respectively, as compared to those in normal human liver. The activities of
DNase
and RNase in the fraction of chromatin protein of human hepatomas, on the contrary, decreased almost to zero. As to the liver of patients with
cancer
of gastrointestinal tract, drastic alterations in the activities of nucleoside kinases and nucleases in the direction characteristic of tumors themselves were observed. This phenomenon is regarded as a manifestation of the systemic effects of the tumor on the host.
...
PMID:[Enzymes of anabolic and catabolic nucleic acid pathways in human hepatomas, in liver of healthy persons, and in liver of patients with cancer of gastrointestinal tract]. 19 26
Retinoic acid-binding protein (RABP) has been detected in the nuclei of chick embryo skin and Lewis lung tumor. The nuclear binding component showed the same ligand specificity and sedimentation value as the cytosol RABP. Whereas pronase completely digested the nuclear binding component,
DNase
showed 40%, and RNase showed negligible digestive action. Retinoic acid binding to the nuclear RABP was completely inhibited by a mercurial, and the inhibition was reversed by dithiothreitol. The nonspecific uptake of retinoic acid by Lewis drug nuclei and chick embryo skin nuclei was inhibited up to 50% by cytosol RABP. The maximal inhibitory effect produced by cytosol RABP was after 45-min incubation. Incubation of Lewis lung tumor with [3H]retinoic acid resulted in the appearance of nuclear RABP: [3H]retinoic acid in the nuclei. The complex formed was weak, and most of the bound retinoic acid could be removed by dialysis.
Cancer
Res 1979 Jul
PMID:Localization of retinoic acid-binding protein in nuclei and the nuclear uptake of retinoic acid. 22 Nov 5
Normal murine spleen cells were sensitized to syngeneic myeloid leukemia cells by RNA extracted from the lymph nodes and spleens of Hartley guinea pigs immunized with the murine leukemia cells. Sensitization mediated by RNA was an active process that required physiologic temperature and at least a 10-minute incubation. RNA extracted from unimmunized guinea pigs of guinea pigs immunized with normal spleen cells failed to sensitize the mouse spleen cells. Sensitization was specifically directed toward leukemia cells, whereas the spleen cells remained unreactive toward normal spleen or bone marrow cells. The sensitizing moiety was RNA itself inasmuch as it was inactivated by RNase and not by
DNase
or pronase. Preparations whose RNA patterns on sucrose density centrifugation gave evidence of degradation of the RNA did not sensitize normal spleen cells. These studies demonstrate that xenogeneic immune RNA can specifically sensitize normal spleen cells to syngeneic myeloid leukemia cells.
J Natl
Cancer
Inst 1979 Jan
PMID:Sensitization in vitro to murine myeloblastic leukemia cells by xenogeneic immune RNA. 28 68
Sera from 134 selected patients with various types of
cancer
were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in
cancer
patients' sera and treatment with
DNase
did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4
cancer
patients showed that the major binding activity was found between 19S and 7S.
J Natl
Cancer
Inst 1977 May
PMID:The C1q binding test for soluble immune complexes: clinical correlations obtained in patients with cancer. 32 5
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