Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of immune RNA treatment on the incidence of death from pulmonary metastases was studied in C57BL/6J mice after excision of a B16 murine melanoma. Immune RNA was extracted from the lymphoid tissues of guinea pigs immunized with B16 tumor and then incubated in vitro with normal C57BL/6J mouse splenocytes. Mice receiving intraperitoneal injections of these RNA-treated syngeneic splenocytes after the primary B16 isograft was resectioned showed significantly improved long-term survival (42 to 67 percent in three successive experiments) as compared to control mice (0 to 20 percent survival) receiving untreated splenocytes. The effect of RNA treatment was tumor-specific and ribonuclease sensitive. The results suggest that immunotherapy with immune RNA may be of benefit to certain patients after surgery for cancer.
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PMID:Prevention of death from metastases by immune RNA therapy. 69 19

A study was made of the levels of ribonuclease (RNase) in human serum, using 2 independently collected banks of samples from Scripps Clinic and Research Foundation and the Mayo Clinic, each bank representing more than 100 individuals. These serum samples originated from a cross-section of normal individuals, smokers, patients with benign tumours, and patients with a variety of neoplasms. Elevated levels of serum RNase occurred in 68% of the samples from individuals with malignant disease. Elevated levels also occurred in 24% of the samples from individuals with benign tumours and in 38% of the smoker controls from the Mayo Clinic serum bank. Using ion-exchange chromatography, pooled sera from normal individuals and cancer patients were fractionated by differential salt elution. Each pool showed 2 distinct peaks of RNase activity, and both peaks were elevated to the same degree in the cancer serum pools. Similar results were obtained after thin-layer-gel isoelectric focusing of both normal and cancer sera; no new species of RNase could be detected in the sera of patients with malignant diseases. The results suggested a generalized nonspecific increase in serum RNase in these patients.
Br J Cancer 1978 Aug
PMID:Serum ribonuclease activity in cancer patients. 69 43

A review of the literature and current biochemical studies is presented which provides significant evidence of alteration in the level of the enzyme ribonuclease activity in cancer. Current studies reveal that 80% of all cancer patients have alteration in ribonuclease activity and that individuals known to be at high risk for the development of cancer also demonstrate significant alteration of ribonuclease activity. It is noted that while elevation of serum ribonuclease exists within the cancer state and appears to be independent of clinical status (relapse, remission, or cured), diminished activity is found within the tumor itself. Animal models are reviewed which demonstrate that ribonuclease activity becomes elevated in the murine species subsequent to the transplantation of tumor and following the infection of the host with oncogenic virus. The occurrence of elevated ribonuclease activity in high tumor incidence strain mice long before the development of overt tumor is alos discussed. To date it is not possible to assign a specific function to the changes in the level of ribonuclease in connection with the cancer state. However, evidence indicating that tumor chemotherapy is generally associated with early elevation of ribonuclease activity within the tumor cell suggests that increased ribonuclease activity may play a role in the process by which the host restricts neoplastic transformation. The potential of this enzyme as a biochemical marker in cancer is discussed.
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PMID:Alteration of human serum ribonuclease activity in malignancy. 75 46

It was shown that normal nonimmune C3H mouse spleen cells became specifically cytotoxic to chemically-induced syngeneic C3H tumor cells by incubation with xenogeneic I-RNA extracted from the lymphoid organs of specifically immunized guinea pigs. This response was specific for the tumor used to immunize the I-RNA donor. In a totally syngeneic system, we showed that syngeneic I-RNA extracted from the spleens of tumor-bearing rats mediated cytotoxic immune reactions which were directed specifically against the tumor-associated antigens of syngeneic rat tumor target cells. Active antitumor I-RNA synthesis in the lymphoid organs of I-RNA donor animals reached a maximum between days 14 and 21, depending on the route of administration and the nature of the immunizing tumor. Active I-RNA preparations were insensitive to treatment with deoxyribonuclease or pronase, but were inactivated by ribonuclease treatment; thereby indicating that the active moiety was one or more species of RNA. The active fractions of the I-RNA preparations had sedimentation values in sucrose density gradients of 12-16S, and comprised only a small fraction of the total RNA present in the lymphoid cells. Active antitumor I-RNA appeared to be localized in the cytoplasm of sensitized lymphoid cells, rather than in the nucleus. Lymphocytes from normal human donors as well as from cancer patients, when incubated with xenogeneic or allogeneic I-RNA, became specifically cytotoxic for human tumor cells in vitro. Crossreactivity among tumors of the same histologic type was observed, but not crossreactivity with tumors of other histologic types. Xenogeneic I-RNA extracted from the lymphoid organs of donor animals immunized either iwth tumor cells or normal tissues, following incubation with normal allogeneic lymphocytes, mediated cytotoxic immune reactions which were directed both against tumor-associated antigens and normal transplantation antigens. However, when autologous lymphocytes were used as effector cells, only immune reactions directed against tumor-associated antigens were observed. Allogeneic I-RNA extracted from peripheral blood lymphocytes of human cancer patients mediated specific cytotoxic immune reactions that were directed against common tumor-associated antigens shared by human tumors of similar histologic type. I-RNA's directed against "self" normal cell surface antigens appear to be recognized as self by lymphocytes, and immune responses against these self antigens are not elicited. On the other hand, I-RNA's directed against "nonself" tumor-associated antigens induce lymphocytes to effect specific antitumor immune responses. Our data are consistent with the hypothesis that I-RNA is an information-containing ribonucleic acid molecule capable of mediating immune reactions in vitro which are specific for the tumor-associated antigens of the tumor used to immunize the I-RNA donor.
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PMID:Mediation of immune responses to tumor antigens in vitro by immune RNA. 107 64

Infusion of cycloheximide i.v., an antibiotic known to inhibit synthesis of protein, at a rate of 0.2 mg/kg/hr, reliably caused lysis of fever in 15 chronically febrile patients with Hodgkin's disease who did not have detectable bacterial, fungal, or viral infection. Antipyretic effects were also seen in some patients with reticulum cell sarcoma, lymphosarcoma, acute leukemia, histiocytic medullary reticulosis, plasma cell myeloma, carcinoma of the lung, and carcinoma of the cervix. The drug failed to produce defervescence in four patients with normal granulocyte reserves, who were febrile due to bacterial infection. When infused at a rate of 0.2 mg/kg/hr, the drug apparently caused an acute alteration of protein metabolism in man in that plasma amino acid nitrogen rose acutely while plasma levels of muramidase and ribonuclease fell during the period of the infusion. The data suggest that continuing synthesis of protein may be involved in nonbacterial fever of neoplastic disease. Mammalian granulocytes and monocytes are known to elaborate a pyrogenic protein following appropriate stimulation; it is suggested that in some types of neoplastic disease, particularly Hodgkin's disease, tumor cells may produce and release a pyrogenic protein and that drug-induced inhibition of its synthesis is responsible for the observed lysis of fever.
Cancer Res 1975 May
PMID:Antipyretic effect of cycloheximide, and inhibitor of protein synthesis, in patients with Hodgkin's disease or other malignant neoplasms. 109 49

The major RNA species present in the purified mitochondrial fraction of the Walker carcinoma were investigated in order to determine which of them are located in the mitochondria and coded by the organelle DNA. The subcellular distribution of these RNA's and the in vivo sensitivity of the transcription process to selective inhibitors were examined. Among the different species separated by polyacrylamide gel electrophoresis, only the 21 and 16 Se RNA's were found exclusively in the purified mitochondria, approximately Se being the S value estimated from the relative electrophoretic mobility of the RNA. A bifid peak observed in the 16-15 Se region was shown to be an artifact caused by the ribonuclease inhibitor, naphthalene disulfonate. Ethidium bromide at high doses inhibited the incorporation in vivo of 32P into 21, 16, and 4 Se RNA, but the nuclear transcription of cytoplasmic RNA was also inhibited to the same extent. No significant effect was observed at lower doses. In contrast, actinomycin D exerted a differential inhibition of the synthesis of 28 and 18 Se RNA from both the cytoplasmic and the mitochondrial fractions, practically without affecting the transcription of the 21 and 16 Se species. The incorporation of 32P into mitochondrial 4 Se RNA was also considerably more resistant to the drug than the synthesis of the cytoplasmic tRNA. It is concluded that the 21, 16, and Se RNA's are the only major discrete species transcribed from mitochondrial DNA present in the Walker carcinoma.
Cancer Res 1976 May
PMID:Identification of the products of mitochondrial transcription in the walker corcinosarcoma by the use of actinomycin D and ethidium bromide. 126 33

Members of the pancreatic ribonuclease (RNase) family have diverse activities toward RNA that could cause them to function during host defense and physiological cell death pathways. This activity could be harnessed by coupling RNases to cell binding ligands for the purpose of engineering them into cell-type specific cytotoxins. Therefore, the cytotoxic potential of RNase was explored by linking bovine pancreatic ribonuclease A via a disulfide bond to human transferrin or antibodies to the transferrin receptor. The RNase hybrid proteins were cytotoxic to K562 human erythroleukemia cells in vitro with an IC50 around 10(-7) M, whereas > 10(-4) M of native RNase was required to inhibit protein synthesis. Cytotoxicity required both components of the conjugate since excess transferrin or ribonuclease inhibitors added to the medium protected the cells from the transferrin-RNase toxicity. Importantly, the RNase conjugates were found to have potent antitumor effects in vivo. Chimeric RNase fusion proteins were also developed. F(ab')2-like antibody-enzyme fusions were prepared by linking the gene for human RNase to a chimeric antitransferrin receptor heavy chain gene. The antibody enzyme fusion gene was introduced into a transfectoma that secreted the chimeric light chain of the same antibody, and cell lines were cloned that synthesized and secreted the antibody-enzyme fusion protein of the expected size at a concentration of 1-5 ng/mL. Culture supernatants from clones secreting the fusion protein caused inhibition of growth and protein synthesis toward K562 cells that express the human transferrin receptor but not toward a nonhuman derived cell line. Since human ribonucleases coupled to antibodies also exhibited receptor mediated toxicities, a new approach to selective cell killing is provided. This may allow the development of new therapeutics for cancer treatment that exhibit less systemic toxicity and, importantly, less immunogenicity than the currently employed ligand-toxin conjugates.
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PMID:Rational immunotherapy with ribonuclease chimeras. An approach toward humanizing immunotoxins. 128 24

We explored the state of the p53 gene in gastric cancer. Using one or more methods, we examined 15 specimens from primary carcinomas (14 tumors, one cell line), five cell lines derived from metastases, and seven paired samples of nonmalignant gastric mucosa. Sequence analyses of complementary DNA containing the entire p53 gene open reading frame demonstrated abnormalities in one of five samples from primary tumors and in all five samples from metastases. The single cell line derived from a primary carcinoma had no abnormality of the gene. The six abnormalities included four point mutations, one base-pair deletion resulting in a frame shift, and a 24 base-pair deletion caused by an intronic point mutation (as determined by sequence analysis of genomic DNA). Four of the six mutations mapped to regions highly conserved among species or involved in simian virus 40 T-antigen binding. Restriction fragment length polymorphism studies confirmed that chromosome 17p allelic deletions occur only in a minority of primary tumors, but that they may occur more frequently in metastases. Northern blotting and ribonuclease protection assays detected only a fraction of the p53 gene abnormalities detected by sequencing. Our findings indicate that mutations of the p53 gene are relatively rare in primary gastric tumors but appear to be relatively frequent in cell lines derived from metastatic lesions. Our results may help in understanding the molecular events associated with progression and metastasis in gastric carcinoma.
J Natl Cancer Inst 1991 Jul 03
PMID:Occurrence of p53 gene abnormalities in gastric carcinoma tumors and cell lines. 167 61

In sensitive cells interferon (IFN) induces many genes leading to an increased production of several different proteins. One of these gene products is the enzyme oligoadenylatesynthetase (OAS). The main effect of this IFN induced enzyme activation is the production of oligonucleotides (2-5A) from cellular ATP. The 2-5A activates an endogeneous ribonuclease (RNase), which cleaves rRNA and mRNA. The sum of these effects is degradation of cellular and viral RNA, resulting in reduced protein synthesis. Taken together, IFN, OAS and 2-5A exist as a part of immune defence system primarily directed against virus infections. Furthermore, it is possible that this system under normal, physiological conditions regulates the growth of somatic cells. The virus inhibiting effect of IFN has been useful in the treatment of viral infections and certain types of cancer. Probably, the IFN dependent enzyme systems will achieve a greater therapeutic significance in the future.
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PMID:[Interferon, oligoadenylate synthetase and oligoadenine nucleotide--a cell biological triad]. 169 81

The anti-cancer drug cis-diamminedichloroplatinum (II) (cis-DDP) reacted with Tetrahymena self-splicing rRNA ribozyme, causing loss of self-splicing activity and formation of a number of platinated RNA species. The formation of one distinct platinated product, migrating at an apparent size of 2400 nt, was closely associated with ribozyme inactivation. This platinated RNA was resistant to T1 ribonuclease digestion, suggesting the presence of inter-strand Pt cross-links. The reaction rate of cis-DDP with the ribozyme followed first order kinetics and showed a saturation effect with increasing cis-DDP concentration, characteristic of an affinity-label type of interaction rather than bimolecular collision. The apparent KI for binding of cis-DDP to the ribozyme was 62 microM. Ribozyme treated with urea was not inactivated by cis-DDP, indicating that the native structure of the RNA is required for reaction with cis-DDP. Mg++, which binds to the ribozyme and causes conformational changes in the molecule, protected the ribozyme from inactivation by cis-DDP and also prevented the formation of platinated RNA. These results suggest that binding of cis-DDP to sites formed by certain secondary or tertiary structural elements of the RNA enhance the rate and the specificity of reaction of the reagent with the ribozyme.
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PMID:Inactivation of Tetrahymena rRNA self-splicing by cis-platin proceeds through dissociable complexes. 190 1


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