Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gag-related proteins found in cells transformed by avian erythroblastosis virus (AEV) and the avian myelocytomatosis viruses MC29 and CMII have been compared by tryptic peptide fingerprinting. A comparison of the methionine-containing tryptic peptides of the AEV 75-kilodalton protein, the CMII 90-kilodalton protein, and the MC29 110-kilodalton protein with the gag gene product Pr76 of their naturally occurring helper leukemia viruses enabled us to distinguish those peptides related to the gag gene from the non-gag-related peptides. The 12 non-gag peptides found in the AEV 75-kilodalton protein were unique to this protein and not found in the MC29 110-kilodalton or CMII 90-kilodalton proteins. In contrast, the MC29 110-kilodalton protein shared two methionine-containing non-gag tryptic peptides with the CMII 90-kilodalton protein. When these experiments were repeated with [14C]lysine and [14C]arginine as the labeled amino acids, the MC29 110-kilodalton protein and the CMII 90-kilodalton protein were found to share 30 out of approximately 40 non-gag-related peptides. These results demonstrate that viruses with a similar transformation spectrum synthesize related proteins and suggest that the gag-related proteins represent the transforming proteins of the replication-defective avian leukemia viruses.
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PMID:Comparative tryptic peptide mapping studies suggest a role in cell transformation for the gag-related protein of avian erythroblastosis virus and avian myelocytomatosis virus strains CMII and MC29. 624 97

The nucleic acid-binding proteins of bovine leukemia virus (BLV) and feline leukemia virus (FeLV) were isolated in a high state of purity with chloroform-methanol extraction followed by reversed-phase liquid chromatography. Selective solubilization and purity of BLV p12 and FeLV p10 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The compositions and molecular weights were determined by amino acid analysis. An abundance of lysine and arginine residues along with their size identifies both BLV p12 and FeLV p10 as small basic proteins similar to well-defined type C viral nucleoproteins. NH2-terminal degradation by the semiautomated Edman method provided the sequence of the first 40 amino acids for both proteins. The putative nucleic acid binding site found in several type C viral nucleoproteins was contained within this sequence, with the most homology centered around an eight-amino acid region involving seven identical residues and one substitution. Antisera were developed in rabbits, and specificity and titers were determined by electroblotting and immunoautoradiography. By this technique, an immunological cross-reaction was found between BLV p12 and FeLV p10. The shared antigenic determinant most likely exists in the highly conserved eight-amino acid region. Although this sequence is also highly conserved in the nucleic acid-binding proteins of murine leukemia viruses, the shared antigenic determinant is not found in these or any other type C viruses tested. It is suggested that substitution of arginine (BLV p12/FeLV p10) to lysine (murine leukemia virus p10) is sufficient to elicit a change in antibody specificity.
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PMID:Structural and antigenic analysis of the nucleic acid-binding proteins of bovine and feline leukemia viruses. 629 55

Previously, in vitro recombinant DNA studies demonstrated that genetic determinants of N-tropism and B-tropism, or Fv-1-related host range properties of murine leukemia viruses, were located in a BamHI-HindIII DNA segment derived from the 5' portion of the cloned viral genome. We sequenced this segment and its immediate 5' region from cloned DNA of two BALB/c mouse C-type viruses (WN1802N and WN1802B) and found base differences at 12 positions out of the otherwise identical 1,390-base-pair sequences. Analysis of the most likely reading frame showed that 6 of the 12 base differences would result in four encoded amino acid changes, three of which occur at positions 109 (glutamine in WN1802N versus threonine in WN1802B), 110 (arginine in WN1802N versus glutamic acid in WN1802B), and 159 (glutamic acid in WN1802N versus glycine in WN1802B) of the p30 protein. The remaining one is located at position 36 (threonine in WN1802N versus isoleucine in WN1802B) of the viral polymerase protein. Significant conformational alteration of the p30 protein could be predicted from these amino acid changes.
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PMID:Nucleotide sequences of gag-pol regions that determine the Fv-1 host range property of BALB/c N-tropic and B-tropic murine leukemia viruses. 631 71

The structural proteins of murine type C retroviruses are proteolytic cleavage products of two different precursor polyproteins coded by the viral gag and env genes. To further investigate the nature and number of proteolytic cleavages involved in virus maturation, we quantitatively isolated the structural proteins of the Rauscher and Moloney strains of type C murine leukemia virus (R-MuLV and M-MuLV, respectively) by reversed-phase high-pressure liquid chromatography. Proteins and polypeptides isolated from R-MuLV included p10, p12, p15, p30, p15(E), gp69, and gp71 and three previously undescribed virus components designated here as p10', p2(E), and p2(E). Homologous proteins and polypeptides were isolated from M-MuLV. Complete or partial amino acid sequences of all the proteins listed above were either determined in this study or were available in previous reports from this laboratory. These data were compared with those from the translation of the M-MuLV proviral DNA sequence (Shinnick et al., Nature [London] 293:543-548, 1981) to determine the exact nature of proteolytic cleavages for all the structural proteins described above and to determine the origin of p10' and p2(E)s. The results showed that, during proteolytic processing of gp80env from M-MuLV (M-gp 80env), a single Arg residue was excised between gp70 and p15(E) and a single peptide bond was cleaved between p15(E) and p2(E). The structure of M-gPr80env is gp70-(Arg)-p15(E)-p2(E). The data suggest that proteolytic cleavage sites in R-gp85env are identical to corresponding cleavage sites in M-gp80env. The p2(E)s are shown to be different genetic variants of p2(E) present in the uncloned-virus preparations. The data for R- and M-p10's shows that they are cleavage products of the gag precursor with the structure p10-Thr-Leu-Asp-Asp-OH. The complete structure of Pr65gag is p15-p12-p30-p10'. Stoichiometries of the gag and env cleavage products in mature R- and M-MuLV were determined. In each virus, gag cleavage products (p15, p12, p30, and p10 plus p10') were found in equimolar amounts and p15(E)s were equimolar with p2(E)s. The stoichiometry of gag to env cleavage products was 4:1. These data are consistent with the proposal that proteolytic processing of precursor polyproteins occurs after virus assembly and that the C-terminal portion of Pr15(E) [i.e., p15(E)-p2(E)] is located on the inner side of the lipid bilayer of the virus.
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PMID:Quantitative separation of murine leukemia virus proteins by reversed-phase high-pressure liquid chromatography reveals newly described gag and env cleavage products. 633 15

On the basis of several physiological properties of L-canavanine, we have tested the prediction that this analogue of arginine would enhance the cytotoxic effects of gamma-rays in mammalian cells. Using the human colonic tumor cell line, HT-29, time-dose studies were performed with log-phase cultures in order to determine conditions which maximize the incorporation of L-canavanine into cellular proteins while leaving a large fraction of the cells viable for subsequent gamma-ray survival measurements. At an input ratio of 2.5 (L-canavanine:arginine), the analogue exerted a cytostatic effect on the cells for at least 6 days following one cell division. Little cell killing (less than 20%) by clonogenicity was caused by L-canavanine during the first 12 hr of treatment of log-phase cells, even at a L-canavanine:arginine ratio of 20. A 24-hr exposure, however, produced an exponential decrease in survival as a function of L-canavanine concentration. The interaction between L-canavanine treatment and gamma-ray damage with respect to cell survival was examined under several conditions and times based on the above findings. Optimal enhancement of X-ray-induced cytotoxicity (assayed by loss of clonogenicity) was observed with a 48-hr exposure to the analogue at a L-canavanine:arginine ratio of 10. A marked increase in radiosensitivity was observed when L-canavanine was administered either before or after irradiation of the cells. In both protocols, enhancement was seen at all radiation doses. Together with our earlier findings showing the antitumor activity of L-canavanine in L1210 murine leukemia, these results suggest the potential usefulness of this amino acid analogue in the treatment of cancer.
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PMID:Enhancement of human tumor cell killing by L-canavanine in combination with gamma-radiation. 687 59

Tuftsin, a physiological tetrapeptide derived from the Fc region of leukophilic IgG possesses a variety of immunopotentiating properties including the ability to act as an immunotherapeutic agent against the experimental tumors, L1210 leukemia and Cloudman S-91 melanoma. Although the mechanism of action of tuftsin in vivo is not known, several types of leukocytes have been shown to become cytotoxic effector cells following activation with tuftsin. These cells presently include macrophages, natural killer cells, and granulocytes. The possibility that tuftsin can also activate other types of effector cells have not been ruled out. We feel this small peptide has a high potential (largely unrecognized) as an antitumor immunopotentiating agent. It is naturally occurring in man and appears to be relatively non-toxic. Its exact sequence (Thr-lys-Pro-Arg) is known and it can be chemically synthesized. Methods are also available to monitor the levels of tuftsin in body fluids. These properties along with its ability to control infectious disease make this agent one of the more promising immunopotentiators.
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PMID:Antitumor effect of tuftsin. 689 73

Some of the properties of the tetrapeptide tuftsin, Thr-Lys-Pro-Arg, are discussed. We describe three phases of tuftsin activation of the macrophage. Tuftsinyltuftsin, the octapeptide Thr-Lys-Pro-Arg-Thr-Lys-Pro-Arg, was synthesized with a view of minimizing the formation of Lys-Pro-Arg, from tuftsin by tissue aminopeptidases. The tripeptide is a tuftsin inhibitor. The octapeptide proved to be quite effective in prolonging the life of syngeneic mice injected with L1210 leukemia cells. Its effect in our laboratory, was considerably better than we could obtain with tuftsin. A simple method for purifying tuftsin by high performance liquid chromatography is described using 0.75% trifluoroacetic acid in water. The tuftsin sequence Thr-Lys-Pro-Arg is present in P12 protein of Rausher murine leukemia virus. A close analog Thr-Arg-Pro-Lys appears in yet another virus protein the haemagglutinin of influenza virus. A second close analog Thr-Arg-Pro-Arg forms the penultimate carboxyterminal of a pancreatic polypeptide found in human and several animals.
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PMID:Tuftsin, a natural activator of phagocytic functions including tumoricidal activity. 689 74

Plasma membranes prepared from rat livers inhibited the in vitro growth of various mammalian cells including hepatoma cells in a concentration-dependent manner, showing almost complete arrest of cell growth at 0.1 mg protein/ml. Some of these cells tested, i.e., leukemia (L1210 and P388) and myeloma (P3-NS-1/1-Ag4-1) cells, were labile in the presence of plasma membranes (losing the viability), and CHO (Chinese hamster ovary) cells became round without detaching from the substratum. The culture medium preincubated with liver plasma membranes no longer supported the growth of hepatoma cells (AHI3 and AH66F). However, the 'conditioned' medium supplemented with L-arginine, supported the growth of the cells. Moreover, the addition of L-ornithine to the cultures containing plasma membranes markedly reduced the inhibitory effect of plasma membranes. The plasma membrane preparations were found to possess considerable arginase activity. There results seem to indicate the possible involvement of arginase in the inhibition of cell growth by liver plasma membranes.
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PMID:Arginase as an inhibitory principle in liver plasma membranes arresting the growth of various mammalian cells in vitro. 720 Aug 4

Melphalan uptake by human ovarian carcinoma cells obtained from patients with clinically documented disease was significantly reduced by ascitic fluid. Examination of the ascitic fluid revealed physiologic concentrations of a number of amino acids, notably leucine (100-150 microM) and glutamine (500-600 microM). These two amino acids, when used at concentrations found in the ascitic fluid, significantly reduced melphalan uptake to levels which approximated those obtained with ascitic fluid. The possible effect of high concentrations of these amino acids on melphalan therapy for this neoplasm is discussed with particular reference to the model melphalan transport system in the murine L1210 leukemia cell. Specific emphasis is placed on the rationale for combining melphalan with arginine and a glutamine-depleting enzyme.
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PMID:Uptake of melphalan by human ovarian carcinoma cells and its relationship to the amino acid content of ascitic fluid. 722 65

Over thirty amino acid and peptide derivatives of the antitumor drug daunorubicin (DM) were tested for their potency to inhibit EL4 leukemia cell growth in mice. The therapeutic effect of the basic amino acids lysine, arginine, ornithine, and 2,4-diaminobutyric acid coupled to the amino group of the DM moiety proved superior to that of the parent drug. The derivatized amino acids and their di- or tripeptides are significantly less toxic than DM, which enabled their administration at much higher doses. Seventy percent to 80% of tumor-bearing C57BL/6 mice were cured by multidose treatment with diaminobutyryl-DM, which was found to be the most efficient derivative.
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PMID:Improved antitumor activity of basic amino acid and dipeptide derivatives of daunorubicin on EL4 leukemia cells in mice. 723 50


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