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 newly synthesized nitrosoureas 1-(2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea (Acetamido-CNU), 1-(2-chloroethyl)-1-nitroso-3-(4-morpholino)-urea (Morpholino-CNU), 1-(2-chloroethyl)-1-nitroso-3-(1-piperidino)-urea (Piperidino-CNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-ethylmethanesulfonate (Ethylmethanesulfonato-CNU) were compared in their chemotherapeutic activity against preterminal rat leukemia L 5222 with BCNU, CCNU, MeCCNU, Chlorozotocin, and Hydroxyethyl-CNU. With respect to the dose range effecting a median survival time of more than 90 days, MeCCNU was superior to the other substances. Chlorozotocin, on the other hand, was the only substance which achieved no cures in this experimental arrangement. From the four newly introduced substances the water-soluble substances Acetamido-CNU and Morpholino-CNU were approximately comparable to CCNU with regard to the dose range effecting a median survival time of greater than 90 days. Piperidino-CNU and Ethylmethanesulfonato-CNU also effected cures; however, only Piperidino-CNU in one dosage effected a median survival time of greater than 90 days.
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PMID:Examination of four newly synthesized 2-chloroethylnitrosoureas in comparison with BCNU, CCNU, MeCCNU, chlorozotocin and hydroxyethyl-CNU in preterminal rat leukemia L 5222. 15 9

After cure of rat leukemia L 5222 in 79 BD IX rats by single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (Hydroxyethyl-CNU) a total of 9 rats (11%) developed secondary malignomas.
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PMID:Development of second malignancies in rats after cure of acute leukemia L 5222 by single doses of 2-chloroethylnitrosoureas. 22 10

This report demonstrates the synergistic killing of murine L1210 leukemia in vitro by BCNU and theophylline as has previously been reported in vivo. Synergism is also seen with the related nitrosourea CNU plus theophylline. As measured on alkaline sucrose gradients and by pH-step alkaline elution, the nitrosourea-induced inhibition of DNA replicon initiation is completely reversed in the presence of theophylline. DNA interstrand crosslinking, the damage which usually correlates with nitrosourea cytotoxicity, is not increased by the combination of nitrosourea plus theophylline. At high nitrosourea doses, this interstrand crosslinking is reduced in the presence of theophylline. At least part of the mechanism of the two-drug synergism is the theophylline release of nitrosourea-induced DNA initiation inhibition. Some of the results have been presented at the Annual Meeting of the American Association for Cancer Research.
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PMID:Theophylline release of replicon initiation inhibition by nitrosoureas correlates with the synergistic killing in L1210 leukemia in vitro. 400 Jan 48

The chemotherapeutic activities of 11 chloroethylnitrosoureas, among them 10 newly synthesized compounds, were investigated in rat leukemia L 5222 and in two neurogenic rat tumors. 1-(4-Amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU, compound 1) and cyclophosphamide (12) served as reference substances. The newly synthesized compounds were 1-(2-chloroethyl)-1-nitroso-3-(2-carboxyethyl)-urea (2-carboxyethyl-CNU, 2), 1-(2-chloroethyl)-1-nitroso-4-methyl-4-formyl-semicarbazide (methyl-formyl-amino-CNU, 3), 1-(2-chloroethyl)-1-nitroso-3-(methylene-2-pyridyl)-urea(methylene-2-pyridyl- CNU, 4), 1-(2-chloroethyl)-1-nitroso-3-(methylene-2-pyridyl)-urea hydrochloride (methylene-2-pyridyl-CNU . HCl, 5) 1-(2-chloroethyl)-1-nitroso-3-(methylene-4-pyridyl)-urea hydrochloride (methylene-4-pyridyl-CNU . HCl, 6), 1-(2-chloroethyl)-1-nitroso-3-(3-pyridino)-urea (pyridyl-3-CNU, 7), 1-(2-chloroethyl)-1-nitroso-3-(3-pyridyl)-urea hydrochloride (pyridyl-3-CNU . HCl, 8), 1-(2-chloroethyl)-1-nitroso-3-[4(2,6-dimethyl-morpholino)]-urea (dimethyl-morpholino-CNU, 9), 1-(2-chloroethyl)-1-nitrosocarbamoyl-morpholine (chloroethyl-nitroso-carbamoyl-morpholine, 10), 1-(2-chloroethyl)-1-nitroso-carbamoyl-2,6-dimethyl-morpholine (chloroethyl-nitroso-carbamoyl-dimethylmorpholine, 11). Against both neurogenic tumors cyclophosphamide was distinctly superior to all nitrosoureas. In leukemia L 5222 all nitrosoureas except compounds 7, 8, 11 effected cures. Remarkable differences in toxicity could be observed between the nitroso compounds investigated.
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PMID:Examination of newly synthesized 2-chloroethylnitrosoureas in preterminal leukemia L 5222 and in two transplanted neurogenic tumors. 628 38

L1210 murine leukemia cells were treated in vitro with the novel antineoplastic agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d] -1,2,3,5-tetrazin-4(3H)-one (M&B 39565), and its interaction with cellular DNA was assessed by alkaline elution. DNA interstrand cross-link and DNA-protein cross-link formation was quantified with regard to drug concentration and length of incubation time after a 2-hr incubation period with drug. Cytotoxicity, as measured by colony formation assays, and DNA damage caused by M&B 39565 were compared with those caused by a breakdown product of M&B 39565, 5-[3-(2-chloroethyl)triazen -1-yl]imidazole-4-carboxamide (MCTIC) and also with 1-(2-chloroethyl)-1-nitrosourea (CNU). Both MCTIC and CNU decompose to yield a 2-chloroethyldiazo species which is capable of alkylating DNA. At equimolar concentrations, all three drugs possessed similar in vitro cytotoxicities; at equitoxic concentrations, they produced similar levels of DNA interstrand cross-linking. The time course for cross-link formation was different for CNU when compared with MCTIC and M&B 39565, with peaks at 6 hr (CNU) and 9 hr (M&B 39565 and MCTIC). This study suggests that M&B 39565 is cytotoxic against L1210 leukemia cells as a consequence of DNA interstrand cross-link formation, probably via its breakdown product MCTIC.
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PMID:Effects of the antitumor agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one on the DNA of mouse L1210 cells. 671 80

The therapeutic activity of a single-dose treatment with 14 2-chloroethylnitrosocarbamoyl derivatives of amino acids (CNU-analogs) in L 5222 rat leukemia is presented. Compounds under study included free carboxylic acids, a methylester, a toluidide, four glucosamides and one derivative of a dipeptide. All substances proved to be active effecting at least an increase in life span of greater than or equal to 120% compared with untreated controls at the optimal dose; 2 compounds effected isolated cures (90-day survivors). Compared with previous data obtained with established and new nitrosoureas under the same conditions, the effectivity of the compounds presented here should be classified, however, only as moderate.
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PMID:Chemotherapeutic activity of 2-chloroethylnitrosocarbamoyl derivatives of amino acids in a transplanted rat leukemia (L 5222). 720 23

The preterminal intraperitoneal implanted rat leukemia L 5222 was used to test the chemotherapeutic activity of 10 newly synthesized nitrosoureas: ethylmethanesulfonato-CNU, acetamido-CNU, dihydroxypropyl-CNU, carboxyethyl-CNU, cyanoethyl-CNU, morpholino-CNU, piperidino-CNU, methylene-dioxybenzyl-CNU, methylene-3-pyridyl-CNU and methylene-4-pyridyl-CNU; their activity was compared against BCNU, CCNU, MeCCNU and hydroxyethyl-CNU. All compounds tested showed a more or less pronounced chemotherapeutic activity. MeCCNU was superior to all other compounds investigated. The predictive value for human tumors of results obtained from a model which is highly sensitive to nitrosoureas is discussed.
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PMID:Examination of newly synthesized 2-chloroethyl-nitrosoureas on rat leukemia L 5222. 744 75