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)

E-N-L-trimethyl lysine (TML) decreases the toxicity of Vincristin, Cyclophosphamide and Doxorubicin (Adriamycin) when administered simultaneously to healthy mice. Simultaneous treatment of L1210 ascites leukemia bearing mice with 100 mg/kg TML and 2, 2.5, 3.2, 3.5, 4 mg/kg Vincristin or 10-15; 20 mg/kg Doxorubicin increases significantly the survival of the animals when compared with untreated and Vincristin or Doxorubicin treated mice. Repeated impulse treatment of S-180 subcutaneous sarcoma with 100 mg/kg TML and 50-100 mg/kg Cyclophosphamide results in a significantly higher surviving time and surviving rate than Cyclophosphamide treatment alone.
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PMID:Combined effect of cytostatic drugs and E-N-L-trimethyl lysine in healthy and transplantable tumor bearing mice. 681 49

A simple method is described for preparing monolayers of non-adherent cells, using concanavalin A to bind the cells to wells of plastic microtest plates. The method was used successfully with all 202 human cell types tested, which included 23 tissue culture lines, 165 fresh specimens of all major histological types of leukemia and lymphoma, 20 fresh myelomas, 2 fresh thymomas, normal spleen and lymph node cells, fractionated T lymphocytes and B lymphocytes from peripheral blood, and cultured fetal amniotic cells. All cell types attached firmly, and were not detached by subsequent vigorous washing. In contrast, attempted attachment of cells in serum free medium, or with poly-L-lysine or glutaraldehyde, was ineffective with many cell types. We used the monolayers as target cells for antibodies to cell surface antigens, utilizing immune rosetting or complement-mediated cytotoxicity. This procedure should simplify most assays involving non-adherent target cells.
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PMID:Preparing monolayers of non-adherent mammalian cells. 686 44

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

6-Ethynyluracil (3) was prepared by two different synthetic procedures. In one approach, 6-formyluracil was reacted with (dibromomethylene)triphenylphosphorane to give 6-(2,2-dibromovinyl)uracil (2), which was silylated and treated with phenyllithium to yield 3. Alternatively, silylated 6-iodouracil was reacted with trimethylsilylacetylene in dry triethylamine in the presence of a palladium/copper catalyst to give 6-[(trimethylsilyl)ethynyl]uracil (5). Compound 5 was converted to 3 in refluxing methanol. At neutral pH, 3 reacted with thiols, such as glutathione, 2-mercaptoethanol, and L-cysteine, but did not react with glycine or L-lysine. This reaction was accompanied by a shift in the UV maximum of 3 from 286 nm to 321-325 nm. The reaction of 3 with 2-mercaptoethanol gave cis-6-[2[(2-hydroxyethyl)-thio]vinyl]uracil as the predominant product. Compounds 2 and 3 inhibited the growth of leukemia L1210, B-16 melanoma, and lewis lung carcinoma cells at concentrations ranging from 1 x 10(-6) to 2 x 10(-5) M. As determined with L1210 cells, the inhibition of growth caused by 2 and 3 was not prevented by the natural pyrimidines, indicating that the agents do not act as antimetabolites.
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PMID:Synthesis and biological evaluation of 6-ethynyluracil, a thiol-specific alkylating pyrimidine. 714 68

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

We have shown that pyridoxal 5'-phosphate is an effective inhibitor of Rauscher leukemia virus DNA polymerase (Biochemistry 15 (1976) 3620). Detailed studies of this inhibition revealed that, in addition to the phosphate and aldehyde groups of pyridoxal phosphate, the presence of a divalent cation is essential for the inhibitory action. The synthesis directed by template primers containing GC base-pairs exhibited more resistance to pyridoxal phosphate inhibition than did that directed by AT base-paired templates. Maximal inhibitory activity of pyridoxal phosphate, however, is noted in the presence of Mn2+, irrespective of which template-primer is used to direct the DNA synthesis. The action of pyridoxal phosphate on the substrate binding site may be deduced from the observations that: (a) only the substrate triphosphate is able to reverse the pyridoxal phosphate-mediated inhibition; (b) the inhibition kinetics exhibit a classical competitive pattern with the substrate; (c) analogous to substrate deoxynucleoside triphosphates the inhibitor is also accepted only in the form of its divalent metal ion complex; and (d) substrate site-specific labeling of RLV DNA polymerase has been shown to occur by linking covalently the pyridoxal phosphate bound to a lysine residue at the substrate binding site.
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PMID:Divalent cation-dependent pyridoxal 5'-phosphate inhibition of Rauscher leukemia virus DNA polymerase: characterization and mechanism of action. 728 79

The antitumor effect of some N alpha-benzyloxycarbonyl-N,N-bis-(2-halogenethyl)hydrazide derivatives of lysine, glycine, cystine, phenylalanine and p-chlorophenylalanine, was studied. Six of eight newly synthesized compounds show considerable antitumor effect on solid Walker carcinosarcoma 256 (about 95% tumor growth inhibition). Three of these compounds under study increased the lifespan of mice with leukemia L1210. The investigation of the effect of N alpha-benzyloxycarbonyl,D,L-phenylalanine-N,N-bis(2-chloroethyl)hydrazine on various mouse tumors showed remarkable growth inhibition of the Ehrlich ascites carcinoma, sarcoma 37, colon adenocarcinoma akatol and lesser antitumor effect also on solid adenocarcinoma 755, Lewis lung carcinoma and melanoma B16. All investigated compounds exhibited depression of leukocyte count--their toxicity being, however, lower than that of sarcolysine in parallel experiments.
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PMID:Antitumor effect of N alpha-benzyloxycarbonyl-N,N-bis-(2-halogenethyl)-hydrazide derivatives of amino acids. 739 53

Insertion of foreign genes into cellular DNA requires (at least one round of) DNA replication. Since hemopoietic stem cells do not divide rapidly, numerous semi-empirically designed multifactor cocktails have been used to stimulate them. In an attempt to find an alternative to this approach we have investigated the effects of the stem cell stimulatory peptide (pGlu-Glu-Asp-Glys-Lys)2, (pEEDCK)2, on progenitor output in murine long-term bone marrow cultures (LTBMC). (pEEDCK)2 may act by inducing growth factor production in stromal cells. Addition of (pEEDCK)2 to LTBMCs resulted in a three-fold increase in CFU-GM production. For showing an effect of (pEEDCK)2 on primitive hemopoietic cells (long-term-culture initiating cells, (LTC-IC)) LTBMCs were depleted of rapidly dividing progenitors by 5-Fluoro-Uracil (5-FU). LTC-IC survive and repopulate the culture with new CFU-GM. (pEEDCK)2 greatly enhanced this process (eight-fold in the second week after 5-FU). Enhanced progenitor production was observed for several weeks even after discontinuation of (pEEDCK)2 additions to the cultures (100-fold, five weeks after 5-FU, three weeks after end of peptide additions). This increase in progenitor production resulted in increased numbers of total nucleated cells. Our results suggest that (pEEDCK)2 may be a useful alternative for multifactor cocktails when proliferation of primitive stem-cell-like cells is required, as in gene therapy and transplantation. Our experiments also indicate that the redox equilibrium between (stem cell inhibitory) monomeric pEEDCK and (stem cell stimulatory) dimeric (pEEDCK)2, which are both endogenous constituents of LTBMCs may play a role in physiological stem cell regulation.
Leukemia 1995 Oct
PMID:Stem cell stimulation in vitro by the dekapeptide (pEEDCK)2: a single-factor alternative for multifactor cocktails. 747 13

We generated variants of the human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) by in vitro selection in MT-4 cells. Portions of flanking protease and integrase sequences as well as the complete reverse transcriptase (RT) open-reading frame of these viruses were cloned and sequenced, using polymerase chain reaction (PCR)-based methods. Mutations were observed at amino acid position 65 (Lys-->Arg; AAA-->AGA) when ddC was employed in the selection procedure and at site 50 (Ile-->Thr; ATT-->ACT) when d4T was used. We confirmed the ability of these mutations to confer diminished sensitivity for these compounds by site-directed mutagenesis, in which these mutations were inserted into the pol gene of infectious recombinant HXB2-D DNA. Viruses that contained the site 65 mutation possessed approximately 5-10 fold resistance against ddC when compared with wild-type HXB2-D. The site 50 mutation conferred approximately 30-fold resistance to d4T in these same assays. Similar results were obtained using primary cord blood lymphocytes in drug resistance assays, indicating that these mutations could confer drug resistance in more than one cell type and that the respective mutations could be expressed in cells of primary origin. No cross-resistance against 3'-azido-3'-deoxythymidine (AZT) was noted for either the site 65 or 50 mutations.
Leukemia 1994 Apr
PMID:Identification of novel mutations that confer drug resistance in the human immunodeficiency virus polymerase gene. 751 78

Using modified nuclear lysis and binding conditions, we have examined the binding of an embryonal carcinoma (EC) cell factor, binding factor A, to a stem cell-specific silencer which acts at the DNA level and overlaps the Moloney murine leukemia virus (M-MuLV) proline primer binding site (PBS). Following our protocol, we found that in vitro binding of factor A correlated with the in vivo activity of the M-MuLV silencer. Factor A bound specifically to the wild-type silencer element at room temperature and 30 degrees C, but not at 4 degrees C, and bound 10-fold better to the full-length silencer than to a minimal silencer core element. The factor was enriched in nuclear compared with cytosolic extracts and in undifferentiated EC cells compared with differentiated cells in which the silencer is nonfunctional. Salt and ion requirements for factor A binding were investigated, and partial purification steps indicated the factor to be a heparin-Sepharose-binding moiety of greater than 100 kDa. To examine possible relationships between silencer and PBS activities, sequences representing phenylalanine, isoleucine, lysine-1,2, lysine-3, methionine, and tryptophan PBS DNA fragments were tested in vivo for stem cell-specific repression of M-MuLV expression and in vitro in DNA binding assays. Of these PBS elements, only the lysine-1,2 PBS DNA fragment showed consistently high levels of repression. Interestingly, the lysine-1,2 PBS DNA fragment also formed a complex with an EC cell factor with characteristics similar to those of factor A. However, the two factors did not cross-compete in binding studies, suggesting that they may be different but related factors. Our results suggest that expression of Mason-Pfizer monkey virus, visna virus, and spumavirus, which use the lysine-1,2 PBS, may be inhibited in undifferentiated stem cells.
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PMID:Stem cell factor binding to retrovirus primer binding site silencers. 752 29


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