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

The antimetabolite 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) has been investigated in an attempt to elucidate its effects on survival time of DBA/2 and B6D2F1 mice with L1210 leukemia and of outbred albino mice with 37 sarcoma. A significant increase in survival time was observed in mice with 37 sarcoma and slight effects were observed in mice with L1210 leukemia when treated with 3 x 12.5 or 3 x 25 mg/kg of 3-oxauracil. No toxic side effects were observed when large therapeutic doses of the drug were given.
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PMID:Testing of 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) in mouse L1210 leukemia and 37 sarcoma. 75 20

Phorbol, the unesterified parent alcohol of the skin promoter TPA, was administered i.p., twice weekly, throughout the lifetime of mice of 7 inbred strains: males and females of AKR/J, C3Heb and BALB/c, and females of SJL/J, DBA/2, SWR and C57BL. A striking difference in strain response was observed, with a pronounced leukaemogenic effect in SWR, a signficiant shortening of the latent period for spontaneous reticulum cell sarcomas (RCNB) in SJL/J, and no demonstrable effect in the other strains. When mice of 3 of the above-mentioned strains (SWR, SJL/J and AKR/J) were thymectomized prior to the beginning of phorbol treatment, different patterns of response were again observed. Thymectomy did not influence the leukaemia incidence in SWR mice, slightly inhibited RCNB development in SJL/J mice and converted phorbol into a leukaemogenic agent for AKR/J mice.
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PMID:Leukaemogenic action of phorbol in intact and thymectomized mice of different strains. 79 8

The toxicity and therapeutic index of cyclophosphamide (CP) in NIH Wwiss and (C57BL X DBA)F mice were affected by the addition of different antibiotics to the drinking water. Penicillin G or Vancomycin increased the rat and number of deaths that followed parenteral treatment with CP; however, penicillin or Vancomycin alone produced no deaths. Both penicillin and Vancomycin changed the normal composition of the gastrointestinal bacteria, thus increasing the antibiotic-resistant coliform bacteria. Neomycin or gentamycin, with or without penicillin or Vancomycin, reduced the number of deaths that followed parenteral treatment with doses of CP lethal to 35% of the animals (LD35). Neomycin and gentamycin reduced the number of coliform bacteria recoverable from the gastrointestinal tract. The doses of CP against L1210 murine leukemia. The combination of CP (LD35) with the aminoglycosides produced several long-term survivors, apparently because larger doses of CP can be used with few drug-related deaths.
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PMID:Effect of antibiotics on mice treated with cyclophosphamide. 79 4

A direct ligand-banding radioassay for methotrexate (MTX) has been developed using dihydrofolate reductase, contained in the lysate of L1210 leukemia cells, as the binding determinant. The procedure is a two-phase reaction system where standard MTX concentrations or the sample being assayed in incubated with the reagent lysate in the first phase, and [3H]MTX is then added in the second phase to titrate the remaining unoccupied binding sites on the enzyme. This method eliminates the need for measuring the residual catalytic activity of the enzyme. The sensitivity of the radioassay is limited only by the specific activity of the [3H]MTX and how approximates 10 pg of the drug. Folic acid, methyltetrahydrofolate, formyltetrahydrofolate, and dehydrofolate in concentrations that are physiological do not interfere in the radioassay. Both mercaptoethanol and reduced nicotinamide andnine dinucleotide phosphate increase the binding capacity of the lysate for MTX; but the reduced nucleotide also increases the affinity of the enzyme for the inhibitor. MTX added to serum can be assayed without extraction if the concentration is greater than 500 pg/ml and recovery of the drug added to serum is about 92%. MTX has been assayed in serum, spinal fluid, and urine of patients who were treated with this drug. It has also been assayed in the lysates of L1210 cells from C57BL X DBA/2 F1 mice treated with MTX. The procedure is simple, rapid, and accurate and should permit better correlation of the therapeutic and toxic effects of MTX with blood concentrations over long-term treatment periods.
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PMID:A direct ligand-binding radioassay for the measurement of methotrexate in tissues and biological fluids. 80 20

We have studied synthesis of specific proteins in two permanent lines of Friend virus-induced erythroleukemia cells (Friend line 745 and Ostertag line FSD-1, both derived from DBA/2 mice). By 96 hr following treatment with 1-2% dimethyl sulfoxide (Me2SO), up to 25% of the protein being synthesized by both these cultures is hemoglobin. At that time, hemoglobin constitutes up to 10% of the cellular soluble protein. Both lines synthesize heme and globin coordinately, and alpha and beta globin chains in a nearly balanced 1:1 ratio. However, the ratio of betaMajor:betaMinor chains synthesized by these induced Friend leukemia (FL) cells is approximately 9 in the FSD-1 line and 1.3 in the Friend Clone 745 line, whereas it is 4 in normal adult DBA/2 mouse erythrocytes. Evidence for the latter conclusion was obtained by electrophoresis of FL hemoglobins on cellulose acetate membranes, and also by chromatographic separation of alpha, betaMajor, and betaMinor globins on carboxymethylcellulose in 8 M urea at 20 degrees C. Carbonic anhydrase activity per mg protein is 3 times higher in induced than in control cultures. 2,3-diphosphoglyceric acid is not found in induced FL cells. Induced and control FL cells agglutinate strongly and equally with Phaseolus vulgaris phytohemagglutinin. The developmental process in these cultured leukemia cells appears to be an aberrant erythropoiesis.
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PMID:Synthesis of erythrocyte-specific proteins in cultured friend leukemia cells. 80 34

A total of 18 compounds consisting of 7 alphatic and 7 aromatic bis(guanylhydrazones), p-quinone-bis(guanylhydrazone), one monoguanylhydrazone, one diamidine and one diguanidine were studied spectrophotometrically to determine their ability to interact with native calf-thymus DNA and the possible correlation of binding with biological activity. In each case, the ability of a compound to bind to DNA correlate with its ability to inhibit the activity of DNA-dependent DNA polymerase (EC 2.7.7.7) extracted from mouse leukemia L1210 cells. For example, all the aromatic bis-guanylhydrazones and diamidine (hydroxystilbamidine), which were good inhibitors of the enzyme activity, showed a biphasic interaction with DNA. All the aliphatic compounds displayed no detectable interaction with DNA in the Tris buffer used, and were also poor inhibitors of the polymerase activity. Interaction of decamethylene diguanide (Synthalin with DNA could not be determined because the compound does not absorb light in the UV-VIS region. However, in similarity with other aliphatic compounds, this agent was a poor inhibitor of DNA polymerase reduction. The p-quinone-bis(guanyl-hydrazone) and p-phenylbenzaldehyde-monoguanylhydrazone showed only a monophasic interaction with DNA and caused an intermediate inhibition of the enzyme activity. When tested for possible anti-leukemic activity against i.p. L1210 leukemia in syngeneic DBA/2J mice, all the aromatic bis-guanylhydrazones as well as hydroxystilbamidine caused prolongation of survival of tumor-bearing mice. Among the aliphatic bisguanylhydrazones, all of which showed no binding to DNA and caused at the most only a very slight inhibition of DNA polymerase, only methylglyoxal-bis(guanylhydrazone) (CH3--G) had antileukemic activity. Synthalin also inhibited leukemia growth. Evidences presented indicate that the mechanisms of action of aliphatic and aromatic bisguanylhydrazones may be quite different. Furthermore, the ability to bind to DNA may be a useful criterion to predict the antileukemic activity of aromatic guanylhydrazones and possibly other aromatic-bis-cationic compounds, but not that of aliphatic congeners.
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PMID:Studies on the structure--activity relationship among aliphatic and aromatic bisguanylhydrazones and some related compounds. 83 65

Six antitumor platinum compounds were used in combination with cyclophosphamide (CY) plus one of five other antitumor drugs in the treatment of advanced (Day 3) L1210 leukemia in (C57BL/6 X DBA/2)F1 mice. The combination of CY with a platinum compound yielded a collective cure rate of 24%; the addition of a third drug to the dual regimen increased the collective cure rate to 55%. The most effective drugs when used in combination with platinum compounds plus CY were, in increasing order of efficacy, 5-fluorouracil, hydroxyurea, and methotrexate. No toxic deaths occurred with any regimen at the dose levels used.
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PMID:Chemotherapy of advanced L1210 leukemia with platinum compounds in combination with other antitumor agents. 87 42

Combined administration of a vaccine consisting of a small number (2 X 10(6)) of L1210 murine leukemic cells treated with glutaraldehyde and concanavalin A and a protein-bound polysaccharide preparation of Coriolus versicolor induced synergistic resistance to L1210 leukemia in BALB/c X DBA/2CrF1 mice. This effect was dependent on the dose and timing of the administration of the protein-bound polysaccharide preparation, being most effective at the time of or 1 day after the second vaccination. Induced resistance was not cross-reactive with P388 murine leukemia, indicating specificity of resistance. This immunopotentiation by the protein-bound polysaccharide did not occur when L1210 cells treated with glutaraldehyde, but not with concanavalin A, were used as a vaccine.
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PMID:Enhanced induction of immune resistance by concanavalin A-bound L1210 vaccine and an immunopotentiator prepared from Coriolus versicolor. 92 33

The structure of the antitumor agent, dichloro(1,2-diaminocyclohexane)platinum(II) (NSC-194814), was modified by replacing the chlorides with organic or inorganic anions. Eighteen new platinum complexes were so isolated and their antitumor properties against the L1210 leukemia in C57BL/6 X DBA/2 mice were evaluated. Most of the complexes were readily soluble in water and some had enhanced antitumor activity compared to the parent dichloro complex. In addition, increased solubility with retention of significant antitumor activity was obtained by oxidizing the parent dichloroplatinum(II) complex with halogen or peroxide to give two platinum(IV) complexes. Some previously reported platinum complexes with phosphorus, selenium, or tellurium electron donor ligands were also synthesized and assessed for antitumor action, but these did not show appreciable activity.
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PMID:Preparation and antitumor evaluation of water-soluble derivatives of dichloro(1,2-diaminocyclohexane)platinum(II). 92 55

By using various protocols of immunization in the xenogeneic system, a serum was produced which contained antibodies against normal as well as leukemic lymphocytes in DBA/2 mice. To obtain specific antibodies capable of recognizing the ML tumor antigen, the best protocol proved to be the one used in group 2, in which immunization with leukemic cells was preceded by immunization of newborn mice with normal lymphoid cells from mice of the DBA/2 f BALB/c/MTV-s-negative strain. The sera contained antibodies capable of identifying the ML antigen in leukemia cells as well as in isolated form.
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PMID:Production of antibodies against ML antigen in the xenogeneic host. 93 52


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