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 in vitro effect of adriamycin (ADR) and lonidamine alone and in combination, at 37 degrees C and 43 degrees C, was investigated on murine leukemia P388 sensitive (P388/S) and resistant (P388/ADR) to adriamycin. The sensitive and the resistant cells were exposed in vitro with and without the drugs for 1 h at 37 degrees C and 43 degrees C. These cells were inoculated ip (10(6) cells/mouse) into groups of BDF1 mice. Cytotoxic effect of the treatment was assessed on the basis of percentage increase in life span (% ILS) of these animals, compared to the animals receiving cells which did not receive any treatment but exposed only to 37 degrees C for 1 h. It was observed that exposure of P388/ADR cells to lonidamine or adriamycin alone at 43 degrees C for 1 h resulted in greater cell kill, thus enhancing the % ILS of the experimental animals receiving those cells, compared to that of mice receiving the cells exposed to the same drugs for 1 h at 37 degrees C. However, the combination of lonidamine (0.02 mM) and adriamycin (10 micrograms/ml) at 43 degrees C for 1 h showed more than a synergistic effect, resulting in a % ILS of 120. Similar results were seen in the case of P388/S; however, the observations pertaining to P388/ADR are encouraging, since the mode of treatment has reversed the acquired resistance of P388 leukemia cells to adriamycin.
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PMID:Potentiation of adriamycin cytotoxicity in P388 murine leukemia sensitive and resistant to adriamycin by use of lonidamine and hyperthermia. 379 66

The antitumor activity of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in P388 ascitic leukemia, disseminated Gross leukemia, and advanced mammary carcinoma. In P388 leukemia, free drug and drug entrapped in liposomes demonstrated equivalent antitumor activity at doses of 2.2 and 4.4 mg/kg, demonstrating 52% and 69% ILS (increase in life-span), respectively. Free doxorubicin at a dose of 10 mg/kg was superior, producing a 185% ILS against 82% with liposomal doxorubicin. With an increase in administered dose the antitumor response with liposomal doxorubicin was much more pronounced; at doses of 20 and 25 mg/kg the ILS was in excess of 376%, with five of ten mice surviving tumor-free. In Gross leukemia, the optimum dose of free doxorubicin, 10 mg/kg, brought about 186% T/C (median survival in treated mice over that in controls, X 100), whereas with liposomal doxorubicin the optimum dose was 16.9 mg/kg, which yielded 214% T/C. In advanced mammary carcinoma, the maximum tumor regression with free doxorubicin was at a dose of 7.5 mg/kg, with two of six mice dying of toxicity. Liposomal doxorubicin caused maximum tumor regression at 10.8 mg/kg dose with no toxic deaths. Doxorubicin entrapped in cardiolipin liposomes was much less toxic than free drug at high doses in normal mice.
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PMID:Antitumor and toxicity evaluation of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes. 394 Feb 17

The antitumor activity of 5-fluoro-2'-deoxyuridine (FUdR) against P388 leukemia was markedly enhanced by addition of guanosine-5'-monophosphate (GMP). With daily i.p. treatment for 5 d, the combination of FUdR at 100 mg/kg/d and GMP at 300 mg/kg/d showed the highest antitumor effect (more than 290% ILS), while maximum ILS of FUdR alone (100 mg/kg/d) was 94%.
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PMID:Potentiation of antitumor activity of 5-fluoro-2'-deoxyuridine by guanosine-5'-monophosphate. 632 64

Mitomycin C (MMC) has been evaluated in combination with several antitumor agents. Full dose response curves were established for all drugs and drug combinations. Synergy was shown with MMC plus either cyclophosphamide (CYC) or methotrexate (MTX). In testing MMC and CYC against P388 leukemia, the combined treatment yielded a 75% rate of long-term survivors at the optimal level, compared to no survivors at the optimal level of the best single agent, CYC, alone. There was no increased toxicity among the combination-treated animals. Large increases in lifespan were obtained against L1210 and B16. Maximally tolerated doses of the single agents could be combined without increased toxicity. The combination of MMC and MTX was synergistic against ip L1210 and P388 leukemias. The responses of mice bearing L1210 to treatment on days 1, 5, and 9 respectively, were 42% ILS for 3.0 mg/kg MMC; 96% ILS for 15 mg/kg MTX; 172% ILS with four out of ten survivors for 3.0 mg/kg MMC plus 15 mg/kg MTX. MMC and adriamycin (ADR) were found to be synergistic against B16 melanoma at one schedule but not against another schedule, or against colon carcinoma 26. No improvements over optimal nontoxic single agent therapy were seen for chlorambucil, 5-fluorouracil, dibromodulcitol, cis-diaminedichloroplatinum or 4-'(9-acridinylamino) methansulfon-M-anisidide. On the basis of these data, recommendations were made for clinical trials for MMC plus either CYC or MTX against lung, breast, and colon tumors.
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PMID:Mitomycin C combination therapy against murine tumor systems. Effectiveness with cyclophosphamide and methotrexate. 640 90

Aliphatic amino acids glycine, alanine, valine, and leucine were conjugated to the antitumor drug N2-methyl-9-hydroxyellipticinium (NMHE) through a peroxidase-catalyzed oxidation reaction. NMR studies of the adducts so obtained have indicated (i) that the amino acids were linked to NMHE between the nitrogen of their primary amine and the C-10 position of the ellipticine ring and (ii) that a double bond was present between the nitrogen and the alpha-carbon of the amino acid moiety. All amino acid-NMHE adducts exhibit a higher lipophilic property than the parent compound (NMHE) directly correlated with the length of the aliphatic chain of the amino acids. The adducts interact with DNA through an intercalating process with apparent binding constant ranging from 2 X 10(5) to 5 X 10(5) M-1 at pH 7.40. The presence of the amino acid moiety linked to NMHE results (i) in a slight decrease of the cytotoxicity on L1210 cells in vitro (ID50 ranged from 0.20 to 0.50 microM) as compared to NMHE (ID50 = 0.05 microM), (ii) in a decrease of the antitumor efficiency in vivo against L1210 leukemia for leucine-NMHE and valine-NMHE (ILS at LD0/2 = 35% and 31%, respectively), (iii) in a suppression of the antitumor activity for alanine-NMHE and glycine-NMHE (ILS less than 25%), (iv) in a strong increase in the bacteriostatic activity on the quaternary ammonium sensitive Escherichia coli BL101 strain and on Salmonella typhimurium TA98 strain. The bacteriostatic effect is directly correlated with the lipophilic property of the drugs. These findings are discussed in terms of a structure-activity relationship.
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PMID:Potential antitumor agents: synthesis and biological properties of aliphatic amino acid 9-hydroxyellipticinium derivatives. 647 Oct 70

We have reported an antitumor aqueous extract from a brown marine alga Sargassum kjellmanianum ("Hahakimoku" in Japanese). Although the extract was effective in the in vivo growth inhibition of the implanted Sarcoma-180 cells, it was not effective against L-1210-bearing mice. In the present study, we attempted to obtain a polysaccharide fraction with antitumor activity against L-1210 leukemia from this alga, on the assumption that the main active substance may be sulfated polysaccharide, especially fucoidan which is mainly composed of L-fucose and ester sulfate. Two kinds of polysaccharide fractions (SKCF and SKCF-F), which contained L-fucose and ester sulfate in the amount of 12.6% and 15.4%, 23.5% and 17.2% respectively, were first prepared starting with extraction with cold-hydrochloric acid, and their antitumor activity was examined. It was found however that they are not effective. Sulfation of SKCF was then carried out. The resulting sulfate (Sulfated SKCF) was observed to contain nearly 50% more ester sulfate than in SKCF and to be effective against L-1210 leukemia showing an ILS value of 26%. Mechanisms of antitumor action of this sulfate were also discussed from the viewpoints of negativity of ester sulfate and of activation of host-mediated immune response as known in antitumor polysaccharide preparations from other sources.
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PMID:Antitumor effect of seaweeds. IV. Enhancement of antitumor activity by sulfation of a crude fucoidan fraction from Sargassum kjellmanianum. 651 98

The antitumor effect of protein-bound polysaccharide, EA6, derived from fruit bodies of Flammulina velutipes (Curt. ex Fr.) Sing., when combined with a vaccine treatment was studied by the challenge test in BDF1 mice and L1210 murine leukemia system. Intensification of the antitumor effect of EA6 was dependent on doses, timing, and frequency of intraperitoneal administration of the material to the immunization by concanavalin A and/or glutaraldehyde treated L1210 vaccine. Administration of EA6 prior to the injection of the vaccine, or repeated injection of more than 4 times did not increase the life span of the animals. But when EA6 was given (40 mg/kg) after the injection of the vaccine, marked prolongation of the life span (ILS of 223%) was observed against challenging of 1 x 10(2) cells of L1210. Combined treatment of EA6 with vaccine exhibited prolonged ILS in the mice challenged with 1 x 10(3) cells of L1210. The specific immunity for L1210 induced by the vaccine was not affected by EA6.
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PMID:Intensification of antitumor-immunity by protein-bound polysaccharide, EA6, derived from Flammulina velutipes (Curt. ex Fr.) Sing. combined with murine leukemia L1210 vaccine in animal experiments. 668 7

The antitumor activity and toxicity of two new 1-beta-D-arabinofuranosyl-cytosine (ara-C) conjugates of cortisol and corticosterone linked through a phosphodiester bond between the 5' and 21 positions of the respective moieties (cortisol- and corticosterone-p-ara-C) were investigated in L1210 lymphoid leukemia cells in mice. They are highly active against both i.p.- and i.c.-implanted ara-C-sensitive lymphoid leukemia in mice, exceeding the activity produced by the parent drug, ara-C. For example, corticosterone-p-ara-C exhibited the respective ILS values of 306% at 50 mg/kg/day X 9 and 294% at 75 mg/kg/day X 9 on survivals of i.p.- and i.c.-inoculated L1210 leukemic mice. The effectiveness of the conjugates seems to depend on schedules of the treatments. The 9-day continuous treatments showed a better therapeutic effectiveness than those with either a 5-day, a single or a widely spaced (q 4d., 1, 5, 9) treatment. However, they were found to be marginally effective against i.p.-implanted ara-C-resistant L1210 leukemia in mice. They were also inhibitory against proliferation of human leukemia-lymphoid cells in culture. Their superior antitumor activity and resistance to cytidine deaminase suggests that they serve as a prodrug form of ara-C or ara-CMP.
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PMID:1-beta-D-arabinofuranosylcytosine conjugates of corticosteroids as potential antitumor agents. 668 55

Sodium cyanate (NaOCN) at a dose of 250 mg/kg was shown to decrease protein synthesis in P388 leukemia tumor cells to approximately 52% of control values at 2 h and 32% at 5 h after NaOCN administration, without a corresponding decrease in various normal tissues of the tumor-bearing CD2Fl mice. CD2Fl mice that had received P388 tumor cells IP 1 day prior to drug administration underwent various schedules of treatment with NaOCN and melphalan (MLN). NaOCN (200 mg/kg or 250 mg/kg) administered IP has no significant antitumor activity (increased mean lifespan [ILS] less than 20%). The simultaneous IP administration of NaOCN (250 mg/kg) plus MLN (15 mg/kg) resulted in a significantly greater antitumor activity (approximately 265% of control, with 21 of 30 animals being long-term survivors) than MLN (15 mg/kg) alone (approximately 156% of control, with 11 of 30 animals being long-term survivors). This synergism was not observed when MLN was administered 4 h after NaOCN administration. The synergistic activity of MLN with NaOCN does not appear to be secondary to alterations in the absorption from the peritoneal cavity into the systemic circulation as determined by 3H2O. NaOCN does not increase the intracellular concentration of [chloroethyl-14C]MLN into P388 cells. The mechanism of the synergistic antitumor activity of simultaneous IP administration of NaOCN and MLN is unknown.
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PMID:Effect of administration of sodium cyanate and melphalan on the lifespan of P388 tumor-bearing CD2F1 mice. 669 30

The synthesis of 10-alkyl analogues of the potent antitumor agent 8,10-dideazaminopterin is described. Alkylation of appropriate alpha-alkyl homoterephthalate esters with 2,4-diamino-6-(bromomethyl)-8-deazapteridine afforded 10-alkyl-10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid diesters. Ester cleavage and decarboxylation at C-10 were accomplished by heating with sodium cyanide in Me2SO at 170-180 degrees C to afford the 2,4-diamino-10-alkyl-8,10-dideazapteroic acids. The acids were coupled with diethyl glutamate, followed by saponification, to give the 10-alkyl-8,10-dideazaminopterins. The compounds were potent inhibitors of growth in folate-dependent bacteria, Streptococcus faecium and Lactobacillus casei. The 10-methyl and 10-ethyl analogues gave the highest percent increases in life span for mice infected with L1210 leukemia with ILS values of +203 and +235%, respectively.
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PMID:Synthesis and antifolate properties of 10-alkyl-8,10-dideazaminopterins. 669 82


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