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)

A standardized extract mainly from rye pollen (Cernilton N) was tested in vitro on the inhibition of prostaglandin and leukotrien synthesis. The determination of the prostaglandin and leukotrien synthesis from labelled arachidonic acid was done in microsomes of ram seminal vesicles resp. in rat basophilic leukemia cells (RBL-1 cells). The water soluble resp. the fat soluble extract fraction from the whole pollen extract were tested separately. The radio-TLC separation of the reaction metabolites showed a dose dependent inhibition of the cyclo-oxygenase and the 5-lipoxygenase activity by the fat soluble pollen extract fraction. The IC50-values are 0.005 mg/ml resp. 0.08 mg/ml and similar to those of the also tested diclofenac. The water soluble fractions showed no effect in this test system. According to these in vitro results and the clinical experience so far with the pollen extract its therapeutic efficacy on benign prostate diseases is best explainable by the anticongestive resp. anti-inflammatory effect of the fat soluble fraction. Due to the different actions of prostaglandins and leucotrienes also relaxant and antiproliferative effects were conceivable.
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PMID:[Inhibition of arachidonic acid cascade by extract of rye pollen]. 190 29

Novel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10-hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HCl salts with the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors. The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods.
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PMID:Synthesis and antitumor activity of 20(S)-camptothecin derivatives: carbamate-linked, water-soluble derivatives of 7-ethyl-10-hydroxycamptothecin. 193 65

A new series of highly water-soluble aminoalkanol platinum(II) complexes have been synthesized and characterized by elemental analysis, conductance, IR, and 195Pt NMR. Preliminary in vitro and in vivo screening tests for antitumor activities of these complexes against L1210 murine leukemia were performed. In general, these compounds were far less cytotoxic than cisplatin and possessed only a moderate degree of antitumor activity.
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PMID:Preparation, characterization, and antitumor activity of water-soluble aminoalkanol platinum(II) complexes. 194 Sep 1

The purpose of the study was to characterize in vivo an immunodepressive murine retroviral 'model' for the possible testing of drugs against HIV infection. Urethane leukaemia virus (ULV) injected into adult BALB/c mice (10(5) focus-forming units/mouse) caused a small, significant splenomegaly from 2 to at least 9 weeks after virus inoculation. Virus was also present in up to 60% nucleated splenocytes (XC 'infectious centre assay'). Effects on splenomegaly and virus in splenocytes were assayed following various regimens of zidovudine given as 0.5 mg/ml or 0.25 mg/ml in drinking water. Regimens included continuous treatment both before and after ULV, only before, and only after ULV inoculation. Zidovudine was also given for a limited period immediately after virus, or initiated after virus infection was established. Zidovudine given continuously at and following ULV infection completely prevented splenomegaly and virus expression in splenocytes. No other regimen was as effective; however, limited zidovudine treatment immediately after virus inoculation greatly reduced the effects of virus, while the same dose initiated after virus infection was established had only a small ameliorating effect. We conclude that ULV may prove to be a useful addition to other available murine systems, and this is discussed.
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PMID:Inhibition of urethane leukaemia virus, a murine retrovirus, in mice by zidovudine. 196 87

Previous studies indicate that decreased serum viral infectivity and viral antigen levels follow oral administration of diethylcarbamazine (DEC) in feline leukemia virus infected cats, even though DEC has not been shown to exhibit in vitro antiviral activity. In this investigation, DEC was given by oral administration or (single dose) IP injection to murine leukemia virus (Cas-Br-M) inoculated mice to permit evaluation of its effect on viral-induced central nervous system disease. The survival of Cas-Br-M inoculated mice receiving DEC in water was significantly prolonged relative to similarly inoculated mice receiving distilled water. Among the Cas-Br-M inoculated mice euthanatized after the study, higher body weights and trend toward less severe brain and splenic lesions were noted in those receiving DEC in drinking water. Given these results, the possible utility of DEC in treatment of retroviral and other infections warrants further study.
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PMID:Effect of administration of diethylcarbamazine on murine leukemia virus (Cas-Br-M) infected mice. 196 4

The Na(+)-dependent transport and facilitated diffusion of uridine were measured after differentiation of HL-60 leukaemia cells along the monocytic pathway by phorbol 12-myristate 13-acetate (PMA). PMA (200 ng/ml) caused a marked increase in Na(+)-dependent uridine transport within 48 h of exposure that was attributable to an increase in transport affinity (apparent Km values of 1.15 +/- 0.22 and 44 +/- 4.4 microM for PMA-induced and uninduced cells respectively), with no change in Vmax. (0.15 +/- 0.02 and 0.13 +/- 0.01 pmol/s per microliter of cell water for PMA-induced and uninduced cells respectively). A corresponding rapid decrease in both the rate of facilitated diffusion and the formation of uracil nucleotides occurred in PMA-induced cells. As a consequence of these changes, intracellular pools of uridine 3-4-fold greater than those in the medium were generated. A similar increase in Na(+)-dependent transport of adenosine, inosine, guanosine, thymidine and cytidine (Km values of 1-4 microM) was observed. The effects of PMA on the activation of the Na(+)-dependent uridine transporter were inhibited by staurosporine, suggesting the involvement of protein kinase C. The findings indicate that a change in the balance of the cellular mechanisms employed for nucleoside transport occurs during the monocytic differentiation of HL-60 leukaemia cells.
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PMID:Induction of the differentiation of HL-60 cells by phorbol 12-myristate 13-acetate activates a Na(+)-dependent uridine-transport system. Involvement of protein kinase C. 200 Dec 55

The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of linker (7-13 bonds), the chemical nature of the linking group (with a carboxamido or an ether function), the position of amino group between the two parts of hybrid molecules, the number of intercalator moieties (ellipticinium) covalently attached to the metalloporphyrin, and the nature of the central metal atom (Mn, Fe, Zn) on the biological activity of these hybrid molecules were studied. In addition, these molecules have a high affinity for double-stranded DNA (affinity constant of hybrid molecule 9Mn,Me = 2.3 x 10(9) M-1 for poly[d(A-T)] and 2.8 x 10(8) M-1 for poly[d(G-C)] and are cytotoxic against murine leukemia cells L1210 in vitro (IC50 of 9Mn,Me = 0.8 microM). Their cytotoxicities are dependent on the nature of central atom. Iron derivatives are less active than manganese analogues and the corresponding zinc derivatives are nearly inactive despite their same affinity for nucleic acids. These highly water-soluble hybrid molecules could be considered as efficient bleomycin models based on a cationic metalloporphyrin.
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PMID:Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin-ellipticine" molecules having a high affinity for DNA. 200 70

The anaemia induced by 3'-azido-3'dideoxythymidine (AZT) is poorly understood. We have used a murine model of AIDS, infection of female C57BL/6 mice with LP-BM5 murine leukaemia (MuLV) virus, to determine if AZT-induced anaemia is due, in part, to decreased responsiveness of erythropoietic precursors (BFU-e) to erythropoietin (EPO). Mice in the early stage of LP-BM5 MuLV disease were given AZT in their drinking water at 1.0 and 2.5 mg/ml. AZT produced anaemia in both groups, in a dose-dependent fashion. Despite the anaemia, the number of splenic and bone marrow BFU-e in AZT treated mice increased up to five-fold over levels observed in infected untreated animals after 15 d of treatment. Colony formation by splenic and bone marrow BFUe was stimulated at lower concentrations of EPO in mice receiving AZT for 15 d than for infected, untreated mice. By day 30, sensitivity of both splenic and bone marrow BFU-e of treated animals returned to that observed from cells of infected untreated animals. The mean plasma levels of EPO observed in AZT treated mice were appropriate for the degree of anaemia observed when compared with phenylhydrazine (PHZ) treated mice. The numbers of BFU-e and the percentage of bone marrow erythroblasts observed were comparable in AZT and PHZ treated mice with similar degrees of anaemia. However, reticulocytosis was inappropriate for the degree of anaemia observed in AZT treated infected mice. AZT-induced peripheral anaemia in the face of increased numbers of BFU-e and increased levels of plasma EPO suggest a lesion in terminal differentiation.
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PMID:Sensitivity of erythroid progenitor colonies to erythropoietin in azidothymidine treated immunodeficient mice. 200 15

The effect of the antitumor complex [Au(dppe)2]Cl (where dppe is Ph2P(CH2)2PPh2) on the overall metabolism of cultured mouse L1210 leukemia cells was investigated by comparing 1H and 31P NMR spectra of perchloric acid extracts of cells incubated for 1 h in the presence and absence of 2 microM [Au(dppe)2]Cl. There were marked (ca. two-fold) increases in the levels of lactate and almost all detectable amino acids suggesting a drug-induced increase in the rate of glycolysis and inhibition of protein synthesis. The levels of taurine and phosphorylcholine were significantly decreased and 31P NMR spectra revealed a depletion of nucleoside triphosphates (NTP). The effect on nucleotide metabolism was investigated further by separating purine and pyrimidine nucleotides and precursors by anion-exchange HPLC. NTP levels were depleted by ca. 70-90% and there was a ca. three- to four-fold increase in nucleoside di- and monophosphates. The effect is postulated to be the result of uncoupling of mitochondrial oxidative phosphorylation. The Cu(I) complex [Cu(Ph2PCH = CHPPh2)2]Cl produced a similar effect on the cellular metabolism but was more potent. The water-soluble complex [Cu(Ph2P(CH2)PEt2)2]Cl caused the accumulation of cellular amino acids at a concentration that did not significantly deplete ATP levels.
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PMID:1H and 31P NMR and HPLC studies of mouse L1210 leukemia cell extracts: the effect of Au(I) and Cu(I) diphosphine complexes on the cell metabolism. 206 26

Four new sugar:mitomycin C derivatives were synthesized by coupling of N-1 of mitomycin C with tetra-O-acetylglucopyranosyl isothiocyanate and 3,4,6-tri-O-acetyl-2-(N-acetylamino)-2-deoxyglucopyranosyl isothiocyanate. Conversion of each derivative to its water-soluble analogue was achieved by deacetylation, using saturated NH3:CH3OH. Antitumor activity, assessed using the in vivo murine P388 ascitic leukemia system, demonstrated efficacy comparable with the parent mitomycin C. However, unlike the highly myelosuppressive parent drug, optimal antitumor activity is achieved at doses which produce only limited leukopenia.
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PMID:New sugar mitomycin C analogues: preparation, murine P388 antitumor activity, and leukopenia induction. 212 4


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