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)

A ribonuclease that hydrolyzes either linear duplex or single-stranded RNA in an exonucleolytic manner has been partially purified from Ehrlich ascites tumor cell nucleoli and is free from other ribonucleases. The enzyme will also degrade the RNA complement of an RNA X DNA duplex; however, no nuclease activity is observed on linear duplex or single-stranded DNA. The exonuclease acts on RNA nonprocessively from the 3' end releasing 5'-mononucleotides. The enzyme has a broad pH optimum around pH 8.0, requires Mg2+ or Mn2+ (0.06 mM) for optimum activity, and is sensitive to ethylenediaminetetraacetic acid and N-ethylmaleimide inhibition. Monovalent cations including K+, Na+, and NH4+ are inhibitory. Gel filtration studies of this enzyme gave a Stokes radius of 40 A. Sedimentation velocity measurements in glycerol gradients yield a S20,W of 6.0 S. From these values a native molecular weight of 100 000 was calculated. Copurification of the single- and double-stranded activities, identical reaction requirements, and identical heat-inactivation curves strongly suggest that both activities reside with the same enzyme.
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PMID:Purification and properties of a novel nucleolar exoribonuclease capable of degrading both single-stranded and double-stranded RNA. 399 80

A cytosolic factor that stimulates transcription in isolated nuclei was purified approximately 4000-fold to near homogeneity from rat liver. The molecular weight of the factor was determined as 47 000 by SDS-polyacrylamide gel electrophoresis. The factor had no detectable deoxyribonuclease and protease activity but showed ribonuclease inhibitor activity. The factor could stimulate transcription in isolated nuclei by 50% at about 3.0 ng and the maximal stimulation was about 100%. When [gamma-S]ATP and [gamma-S]GTP were included in the reaction, the factor stimulated the synthesis of RNA which was able to bind to a mercury-Sepharose column and about 80% of the bound RNA was sensitive to a low concentration of alpha-amanitin. When heparin was added before initiation to preincubation mixture containing RNA polymerases II and DNA, a small but definite incorporation of [14C]UTP was observed. The factor alone had no stimulatory effect on the heparin-resistant incorporation of [14C]UTP but, in the presence of two rat liver nuclear fractions, phosphocellulose 0.5 and 1 M KCl step fractions, could stimulate the incorporation above the level with the combination of the two nuclear fractions. Antibody raised against the factor inhibited accurate transcription from the adenovirus 2 major late promoter in a nuclear lysate from Ehrlich ascites tumor cells, and the inhibition was neutralized by the factor.
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PMID:Purification of a cytosolic factor from rat liver that stimulates transcription in isolated nuclei and its action on purified RNA polymerase II-DNA system. 407 43

Tumor angiogenesis factor (TAF) and its importance in determining a strategy for cancer chemotherapy are discussed. It is suggested that inhibition of RNA synthesis or increased RNA catabolism might interfere with the metabolism of solid tumor cells more so than in normal cells, and thus hinder angiogenesis and pursuant tumor growth by preventing the synthesis of the RNA component of TAF. An attempt is made to indicate potential models for anti-angiogenesis agents of this type. The drugs offered as initial prototypes for investigations along these lines are actinomycin D (which likely has antimetabolite and anti-angiogenesis activities), polyriboinosinic-polyribocytidylic acid (which likely has adjuvant and anti-angiogenesis activities) and ribonuclease (which in theory might be a purely anti-angiogenetic agent). It is noted that these models may turn out to be less than ideal as therapeutic agents due to problems of toxicity, metabolism, potency, or distribution, but nonetheless might serve to yield insights into the design of new cancer chemotherapeutic drugs. In addition, some evidence is cited suggesting that actinomycin D may be more effective against certain tumors when employed in lower, chronic dosages rather than its present use in "loading" dosages.The concept of anti-angiogenesis agents as fundamentally "tumoristatic" therapies is discussed, and the likelihood that such agents might be effectively "tumoricidal" in immunocompetent hosts is mentioned. The main promise of an anti-angiogenetic strategy is efficacy against presently intractable slowly growing human cancers when used in combination with other treatment modalities. In summary, a strategy of cancer chemotherapy predicated upon interference with RNA synthesis or increase in RNA catabolism is offered as a potential mechanism for establishing anti-angiogenesis, and as a promising alternative and adjunct to present methods.
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PMID:Tumor angiogenesis factor. Speculations on an approach to cancer chemotherapy. 413 28

Increase of infectivity for embryonated eggs was observed in Ehrlich ascites tumor cells after intraperitoneal inoculation of Sendai virus into tumor-bearing mice. Virus-induced actinomycin-resistant ribonucleic acid consisting of 14S, 18S, 22S, 35S, and 48S was synthesized, and S antigen was produced in infected cells. The infectivity was suggested to be due to viral ribonucleoprotein for the following reasons: (i) the infectivity was unaffected by V antiserum but was abolished by whole hyperimmune serum, (ii) the infectivity was resistant to ribonuclease, (iii) virus particles were found neither in cells nor on red blood cell stroma treated with cellular extracts, (iv) structures similar to Sendai virus ribonucleoprotein with a maximal length of 10,500 A were observed in cellular extracts.
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PMID:Infective substructures of Sendai virus from infected Ehrlich ascites tumor cells. 430 95

A sensitive and quantitative nucleic acid hybridization assay for the detection of radioactively labeled avian tumor virus-specific RNA in infected chicken cells has been developed. In our experiments we made use of the fact that DNA synthesized by virions of avian myeloblastosis virus in the presence of actinomycin D (AMV DNA) is complementary to at least 35% of the sequences of 70S RNA from the Schmidt-Ruppin strain (SRV) of Rous sarcoma virus. Annealing of radioactive RNA (either SRV RNA or RNA extensively purified from SRV-infected chicken cells) with AMV DNA followed by ribonuclease digestion and Sephadex chromatography yielded products which were characterized as avian tumor virus-specific RNA-DNA hybrids by hybridization competition with unlabeled 70S AMV RNA, equilibrium density-gradient centrifugation in Cs(2)SO(4) gradients, and by analysis of their ribonucleotide composition. The amount of viral RNA synthesized during pulse labeling with (3)H-uridine could be quantitated by the addition of an internal standard consisting of (32)P-labeled SRV RNA prior to purification and hybridization. This quantitative assay was used to determine that, in SRV-infected chicken cells labeled for increasing lengths of time with (3)H-uridine, labeled viral RNA appeared first in a nuclear fraction, then in a cytoplasmic fraction, and still later in mature virions. This observation is consistent with the hypothesis that RNA tumor virus RNA is synthesized in the nucleus of infected cells.
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PMID:Quantitative determination and location of newly synthesized virus-specific ribonucleic acid in chicken cells infected with Rous sarcoma virus. 435 Jul 19

The association between certain cellular RNAs and purified RNA tumor viruses prompted us to examine the possibility that specific host messenger RNAs might also be incorporated into RNA tumor viruses. Using a mouse cell line infected with Friend leukemia virus, T-3-Cl-2, which can be induced to accumulate mouse-globin messenger RNA, we show that mouse-globin messenger RNA sequences are present in viral particles purified from the culture medium of globin-producing cells. These globin messenger RNA sequences are absent from viral particles derived from T-3-Cl-2 cells that are not producing globin messenger RNA. Virus-associated globin messenger RNA sequences sediment in association with the 60S viral RNA complex as well as in free, 9S form. However, under mild denaturing conditions which result in the conversion of viral 60S RNA to 30S and smaller forms, all the globin sequences sediment as 9S RNA. Appropriate control experiments indicate that the virus-associated globin messenger RNA is resistant to degradation by exogenous ribonuclease; that exogenously added globin messenger RNA does not become associated with the 60S viral RNA complex; and that globin messenger RNA can be detected in virions derived from cells both induced for and constitutively synthesizing globin messenger RNA.
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PMID:An association between globin messenger RNA and 60S RNA derived from Friend leukemia virus. 452 26

The growth of tumor isografts in inbred mice is inhibited by intra-peritoneal injections of syngeneic spleen incubated, in vitro, with ribonucleic acid extracted from guinea pigs immunized with the same mouse tumor. This inhibition is partially tumor-specific. Treatment with ribonuclease abolishes the response.
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PMID:Mediation of immunity to tumor isografts in mice by heterologous ribonucleic acid. 543 85

The transplantable pancreatic acinar carcinomas of rat established recently provide useful model systems to examine the composition of secretory proteins as well as the secretory process in transformed pancreatic exocrine epithelium. The neoplastic acinar cells exhibit considerable variation in the extent of cytodifferentiation. In the present study the enzymatic profile of this heterogeneous tumor cell population has been investigated by the indirect immunofluorescent technique using antibodies against six pancreatic enzymes. By immunofluorescence, all neoplastic cells stained positively for the six enzymes tested: amylase, lipase, carboxypeptidase A, chymotrypsinogen, trypsinogen, and ribonuclease. Some variability in the intensity of immunofluorescence was noted, suggesting possible quantitative differences in the content of a given enzyme among tumor cells. These observations suggest that neoplastic acinar cells with or without secretory granules contain secretory proteins, but to a variable extent.
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PMID:Immunohistochemical localization of pancreatic exocrine enzymes in normal and neoplastic pancreatic acinar epithelium of rat. 616 57

Pyronin Y (PY) was used, in flow cytometric (FCM) systems, to estimate the RNA content per cell in formalin fixed EL4 leukosis tumor cells, enzyme dispersed R3327-G rat prostatic adenocarcinoma cells, mouse spleen cells stimulated with concanavalin A, and human peripheral blood lymphocytes stimulated with phytohemagglutinin. Preincubation of the cells with methyl green (MG) blocked PY binding to DNA such that the intracellular fluorescence from MG-PY was due primarily to its binding to RNA. Treatment of the cells with ribonuclease resulted in a 3- to 5-fold reduction in the fluorescence intensity of intracellular MG-PY. Mitogen stimulation of either mouse or human lymphocytes resulted in an increase in DNA (propidium iodide fluorescence) and RNA (MG-PY fluorescence) content per cell over resting levels. Further, the changes in stimulated human lymphocyte DNA and RNA contents following 24, 48, and 72 hr of cell culture were monitored. The results showed that RNA levels were significantly increased prior to that of DNA. Also, the effects of different cell cycle phase specific blocking agents on lymphocyte cell cycle traverse were investigated. We found that: a) actinomycin D inhibited the increases in cellular RNA and DNA; b) hydroxyurea inhibited the increases in cellular RNA were only slightly reduced; c) tritiated thymidine caused an accumulation of cells having high DNA and RNA contents; and d) Colcemid promoted an accumulation of cells having high DNA contents while causing a reduction of cells having high RNA contents. These results were nearly identical to reports by other investigators using the metachromatic dye acridine orange to quantitate RNA per cell. Thus, the MG-PY technique described is indicated to provide a stable and accurate measure of RNA content per cell.
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PMID:Flow cytometric analysis of RNA content in different cell populations using pyronin Y and methyl green. 618 Aug 73

We have examined the secretogogue responsiveness and the pattern of secretory proteins produced by a transplantable rat pancreatic acinar cell tumor. Dispersed tumor cells were found to discharge secretory proteins in vitro when incubated with hormones that act on four different classes of receptors: carbamylcholine, caerulein, secretin-vasoactive intestinal peptide, and bombesin. With all hormones tested, maximal discharge from tumor cells was only about one-half that of control pancreatic lobules, but occurred at the same dose optima except for secretin, whose dose optimum was 10-fold higher. Biochemical analysis of secretory proteins discharged by the tumor cells was carried out by crossed immunoelectrophoresis and by two-dimensional isoelectric focusing-SDS polyacrylamide gel electrophoresis. To establish a baseline for comparison, secretory proteins from normal rat pancreas were identified according to enzymatic activity and correlated with migration position on two-dimensional gels. Our results indicate that a group of basic polypeptides including proelastase, basic trypsinogen, basic chymotrypsinogen, and ribonuclease, two out of three forms of procarboxypeptidase B, and the major lipase species were greatly reduced or absent in tumor cell secretion. In contrast, the amount of acidic chymotrypsinogen was notably increased compared with normal acinar cells. Although the acinar tumor cells are highly differentiated cytologically and express functional receptors for several classes of pancreatic secretagogues, they show quantitative and qualitative differences when compared with normal pancreas with regard to their production of secretory proteins.
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PMID:Biochemical analysis of secretory proteins synthesized by normal rat pancreas and by pancreatic acinar tumor cells. 618 2


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