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)

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

Certain psychotropic drugs when combined with caffeine significantly enhanced the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea in murine leukemia L1210. Enhancement required that all three drugs be given together and optimal results were obtained when the psychotropic drug was given 6 hours before 1,3-bis(2-chloroethyl)-1-nitrosourea and caffeine. Thus, 1,3-bis(2-chloroethyl)-1-nitrosourea alone or with caffeine resulted in 5% cures. Addition of chlorpromazine increased the cure rate to 51% while prochlorperazine gave 30% cures. Chlordiazepoxide produced 39% cures while the dibenzazepine compounds studied were ineffective. For the phenothiazine, benzodiazepine and dibenzazepine compounds studied, tentative conclusions could be drawn on the relationship of chemical structure to enhancing activity. For phenothiazines, the substituent in the R2 position of the phenothiazine ring determined activity to a greater extent than did the substituent in the R1 position. For the benzodiazepine compounds, chlordiazepoxide was superior to diazepam. Although the mechanism of action of psychotropic drugs in this system is unknown, these preliminary results suggest the possibility of a change transfer reaction between the free radical form of the psychotropic drug and one or more intracellular constituents.
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PMID:Enhancement of the antitumor effect of 1,3-bis(2-chloroethyl)-1-nitrosourea by various psychotropic drugs in combination with caffeine. 24 17

We assayed the femoral marrows of individual AKR mice for leukemia colony-units (LCFU) after treatment with amphotericin B (AmB) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with BCNU alone. No differences between the groups were noted in the first 7 days after treatment. All the mice treated with BCNU alone were dead by day 8, and all the survivors among the animals receiving AmB and BCNU retained high levels of LCFU for 2 more days; these LCFU were subsequently rejected by the host. By day 12, LCFU were undetectable. Histologic examination of organs from the same mice on day 5 showed fewer leukemia cells in the mice treated with the combination of agents. In all treatment groups, mice dying of leukemia early (by day 9) had systemic leukemia and most had central nervous system (CNS) involvement. All animals dying between days 10 and 14 had CNS leukemia, but few had systemic leukemia; at later times, though few animals died, they invariably had CNS leukemia without systemic involvement.
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PMID:Growth and rejection of leukemia cells in individual mice after combined treatment with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea. 27 27

The chemotherapeutic activity of eight nitrosourea derivatives was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in transplantable rat leukemia L5222 cells. Bifunctional 1,1'-polymethylenebis-3-(2-chloroethyl)-3-nitrosoureas effected cure rates between 30 and 75% in single equitoxic doses in the therapy of advanced ip implanted L5222 [staging of L5222 leukemia development (hr before median day of death in controls): early = greater than 120; advanced = 120--61; late = 60--25; and preterminal = 24--0]. Of three water-soluble monofunctional alkylating 1-(omega-hydroxyalkyl)-3-nitrosoureas, 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea yielded more cures (90%) than did BCNU (cure rate, 70%) and was also superior to the other substances. Against preterminal ip implanted and late intracerebrally implanted L5222, the hydroxyethyl compound was significantly superior to BCNU.
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PMID:Chemotherapeutic activity of new 2-chloroethylnitrosoureas in rat L5222 leukemia: comparison of bifunctional and water-soluble derivatives with 1,3-bis(2-chloroethyl)-1-nitrosourea. 62 53

A murine model of immune responsiveness had been adapted to study anergic conditions associated with neoplasia. Marked anergy observed in mice bearing L1210 leukemia and P-388 lymphoma is contrasted to the minimal immune depression associated with B-16 melanotic melanoma and Sarcoma 180J. The ability of N,N-bis(2-chloroethyl)-N-nitrosourea chemotherapy to reduce tumor burden without prolonged suppression of delayed cutaneous hypersensitivity is compared to the profound suppression of the cutaneous response observed with Adriamycin cytoreductive therapy. The applications of our model are discussed in relation to tumor-associated anergy, new approaches to the evaluation of pharmaceuticals, and studies of combined chemoimmunotherapy regimens.
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PMID:Delayed cutaneous hypersensitivity to oxazolone in mice with tumors. 63 44

1,1'-Ethylene-bis(1-nitrosourea) (EBNU) posesses antitumor activity against leukemia L-1210. Chemical stability, alkylating activity, and lipophilicity of EBNU and related compounds were compared. EBNU was the most unstable among several bis-N-nitrosoureas and mono-N-nitrosoureas tested. The alkylating activity of EBNU was the same as that of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), but higher than those of other bis- and mono-N-nitrosoureas except 1-methyl-1-nitrosourea. Lipophilicity of EBNU was extremely low compared with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and CCNU.
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PMID:Chemical stability, alkylating activity, and lipophilicity of 1,1'-ethylene-bis(1-nitrosourea) and related compounds. 64 Mar 22

The synthesis of approximately 80 cyclic or acyclic analogs of cyclophosphamide, isophosphamide, triphosphamide, and phosphoramide mustard is outlined briefly. All of the analogs contain at least one 2-chloroethyl or bis(2-chloroethyl)-amino group bound to phosphorus. Representatives of some of the various classes of analogs were evaluated against murine L1210 leukemia in vivo. Some of the cyclic oxidized derivatives and a phosphorodiamidic chloride yielded long-term survivors. 4-Peroxycyclophosphamide was also active against ic implanted L1210 leukemia and against two other murine tumors, Lewis lung carcinoma and C3H mammary tumor.
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PMID:Synthesis and structure-activity relationships of pre-activated analogs of cyclophosphamide (NSC-26271). 94 26

Phenlethylbiguanide (phenformin) a commonly used antidiabetic medication has been found to enhance the antitumor effect of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) in advanced subcutaneously implanted murine L1210 leukemia. Enhancement required two doses of phenformin given twelve to 18 hours apart, the treatment starting either before or after BCNU administration. With BCNU alone median survival (MS) was 18 days with 5% cures. BCNU plus phenformin, in optimal dose and schedule, gave a MS of 25 days with 29% cures. Th mechanism of action of phenformin is unknown but may involve several established metabolic effects of this drug.
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PMID:Enhancement of the antitumor effect of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) by phenylethylbiguanide (phenformin). 102 59

This study presents results of single-drug and combination chemotherapy of the transplantable acute leukemia L5222 in BD IX rats. In leukemia L5222 there is a direct relationship between the number of transplanted cells and mean life expectancy. After single-drug therapy with L-asparaginase, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cyclophosphamide, cytosine arabinoside, daunomycin, 6-mercaptopurine, methylglyoxal bis(guanylhydrazone) dihydrochloride, prednisolone, or vincristine, the best therapeutic effect was observed with BCNU and cyclophosphamide. A massive-dose therapy with BCNU repeated twice or a conbination of vincristine with cyclophosphamide or BCNU with cyclophosphamide yielded a high percentage of cures. Morever, leukemia L5222 seems to be suitable for studying the influence of drugs on the proliferation kinetics of leukemia cells.
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PMID:Chemotherapy of the transplantable acute leukemia L5222 in rats. 112 Mar 7

We have developed a chemoimmunotherapy regimen for the treatment of L1210-cell-induced ascites tumors in mice using a combination of sub-toxic doses of interleukin-2 (IL-2) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU is administered intraperitoneally 4 days after tumor implantation and followed 2 days later by single doses of human recombinant IL-2 for 3 consecutive days. An optimum survival of 84% was achieved using 1500 U IL-2. Reduced survival was observed when lower or higher IL-2 dosages were used. No therapy resulted when heat-inactivated IL-2 was used or when IL-2 was used without chemotherapy. Surviving animals were resistant to L1210 leukemia but not P815 mastocytoma tumor challenge suggesting the combined BCNU/IL-2 therapy stimulated tumor-specific immunity.
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PMID:1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU)/interleukin-2 chemoimmunotherapy of murine L1210 leukemia. 153 59


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