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 mode of transport of a nonphosphorylated adenosine analog, 5'-deoxyadenosine, was studied in murine leukemia L1210 cells. This compound is not subject to the action of intracellular nucleoside-trapping kinases, and its transport can be examined without regard for effects of experimental conditions on kinase activity. Accumulation of 5'-deoxyadenosine was rapid, and nonconcentrative, with equilibrium attained within 12 s at 37 degrees. Kinetic studies were carried out at 20 degrees. We found both a nonmediated (diffusion) and a mediated transport process. The latter had an apparent Km fo 115 micrometer, Vmax = 105 pmol/10(6) cells/min. Uptake of 5'-deoxyadenosine was inhibited by several heterologous nucleosides including adenosine, 2'-deoxyadenosine, thymine riboside, and inosine. Like 2'-deoxyadenosine, 5'-deoxyadenosine was more lipid-soluble than adenosine (from octanol/water partition studies). Compared with 5'-deoxyadenosine, adenosine had a much lower apparent Km (5 micrometer) and a higher Q10 over the 27-37 degrees range (3.0 versus 1.3). Data obtained with adenosine might, however, reflect properties of intracellular adenosine kinase interacting with a transport process.
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PMID:Transport of a nonphosphorylated nucleoside, 5'-deoxyadenosine, by murine leukemia L1210 cells. 20 33

Butylated hydroxytoluene (BHT), pretreatment of 8-wk-old BALB/c mice for 28 days protected against 30-day lethality by X-rays, diethylnitrosamine (DEN), dimethylnitrosamine (DMN) and ethyl methanesulfonate (EMS) but not against methyl methanesulfonate (MMS). In X-ray survivors, neither mean survival nor leukemia incidences were affected by BHT. However, BHT (lifetime), given alone or with DEN (300 MG/KG BW in H2O) or 250 R X-rays, increased irradiated survivors at 18 months but not leukemia or tumor incidences. BHT + DEN treated females had increased survival and a decreased frequency of forestomach squamous carcinomas compared with DEN alone; no differences were seen in males or in pulmonary adenomas. In X-ray + DEN treated females, effect upon survival was additive, but the specific diseases causing this effect were not identified.
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PMID:interactions of ionizing radiation, nitrosamines, sulfonoxyalkanes and antioxidants as they affect carcinogenesis and survival in mice. 21 Jun 45

The effect of leupeptin on the induction of lymphoblastic leukemia in ICR/JCL female mice by N-nitrosobutylurea (NBU) was investigated. NBU was given as a 0.02% solution in drinking water for 10 weeks. A 0.1% concentration of leupeptin was given in the diet. Group A was fed on the leupeptin diet from the beginning, Group B received it after the end of NBU treatment, and Group C was fed on a leupeptin-free control diet throughout. The average periods in the appearance of leukemia in groups A, B, and C were 115+/-50, 112+/-43, and 100+/-17 days (mean+/-SD), respectively, and there was a significant difference between groups A and B and Group C at P less than 0.001. In regard to this point, leupeptin might have the effect of retarding the rpocess of leukemogenesis. However, leupeptin showed no effect on the incidence and histopathological finding of leukemia.
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PMID:Effect of leupeptin on induction of lymphoblastic leukemia in mice by N-nitrosobutylurea. 26 41

The occurrence of a granulocytic leukemia in 1 of 40 female strain 13/N guinea pigs given N-nitroso-N-butylurea continuously in their drinking water for 21 weeks is reported here. This leukemia has been successfully transplanted in this guinea pig strain for 13 transplant generations by i.p. inoculation of leukemic blood or marrow cells. Macroscopically and microscopically, this leukemia resembles the chronic myelogenous form in humans. Histochemical studies showed, however, that unlike the human leukemic cells those in the leukemic guinea pigs are alkaline phosphatase positive. Electron microscopic studies of the guinea pig leukemic cells revealed the presence of numerous intracisternal A-type particles that are not found in corresponding normal leukocytes.
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PMID:Transplantable granulocytic leukemia in strain 13 guinea pigs. 27 Oct 42

Water-soluble monoethers of sucrose and fatty acids were obtained from Trypanosoma lewisi and Astasia longa. The maximum tolerated dose of the preparations on their single intraperitoneal administration was more than 25 g/kg. The doses of 10--40 mg/kg were used repeatedly in therapy. Carcinoma 755, Lewis carcinoma, sarcoma 45, sarcoma 37 and sarcoma 180 were sensitive to the preparations. The preparations were inactive against experimental leukemia.
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PMID:[Antitumor activity of fatty acid derivatives isolated from protozoa]. 33 51

A novel nitrosourea derivative, methyl-6-[[[(2-chloroethyl)nitrosoamino]carbonyl]-amino]-6-deoxy-alpha-D-glucopyranoside (MCNU), is a water-soluble compound in which a methoxyl group is attached to the C-1 position and an N-(2-chloroethyl)-N-nitrosoureido group is attached to the C-6 position of the glucose moiety. MCNU exhibited a marked life-prolongation or growth-inhibitory effect against mouse L1210 leukemia, adenocarcinoma 755, Nakahara-Fukuoka sarcoma, Lewis lung carcinoma, and B16 melanoma. Ip, oral, or iv administration of MCNU was markedly effective against L1210 leukemia, and the therapeutic ratio by ip administration was larger than that of chlorozotocin or CCNU. The life-prolongation effect of MCNU against established Lewis lung carcinoma was similar to that of methyl-CCNU. The bone marrow toxicity of MCNU was less than that of CCNU but considerably more than that of chlorozotocin.
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PMID:Biologic activity of MCNU: a new antitumor agent. 46 55

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

The antitumor activity and toxicity of N-trifluoroacetyladriamycin-14-valerate (AD 32) dissolved in 10% Tween 80 in distilled water were compared to those of adriamycin dissolved in distilled water in 10% Tween 80 in distilled water, in mice bearing L1210 leukemia, P388 leukemia, Gross leukemia, and solid Sarcoma 180. Treatments were performed ip or iv according to different schedules. The antitumor-activity of AD 32 was not superior to that of adriamycin. The antitumor activity of adriamycin dissolved in aqueous solution of Tween 80 was higher than that of adriamycin dissolved in distilled water after after iv treatment.
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PMID:Antitumor activity of N-trifuloroacetyladriamycin-14-valerate. 62 88

A series of N-deacetyl-N-glycosylalkylthiocolchicines (glucosyl, galactosyl, mannosyl, ribosyl, and arabinosyl) was prepared by heating N-deacetylalkylthiocolchicines with the appropriate monosaccharides in methanol. Some compounds (glucosyl-, mannosyl-, and ribosylalkylthiocolchicines) were per-O-acetylated in dry pyridine with acetic anhydride. The compounds were tested against leukemia L-1210 and P-388 systems. Preliminary results showed that the antileukemic activity of the glycosyl compounds in vitro is similar to that of the N-deacetylalkylthiocolchicines used for their preparation. However, the presence of a glycosyl moiety in the molecule gives the advantage of greater solubility in water. Of the results obtained to date in lymphoid leukemia screening in vivo, five glycosyl compounds showed promising activity levels and have now reached confirmed active status.
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PMID:Synthesis and evaluation of N-deacetyl-N-glycosylalkylthiocolchicines as antileukemic agents. 64 31

Ellipticine, a poorly water-soluble alkaloid, is active in several experimental tumor systems. Marked solubility increases were produced by polyvinylpyrrolidone of varying molecular weights (10,000--160,000) and were optimal (approximately 13 mg/ml at 25 degrees) with polyvinylpyrrolidone mol. wt 10,000. Dissolution of ellipticine--polyvinylpyrrlidone (1:22 w/w) tablets in simulated gastric juice was superior to that of ellipticine hydrochloride polymers without affecting maximum dissolution at 37 degrees. Physiological disposition of ellipticine--polyvinylpyrrolidone was compared with that of the hydrochloride salt and ellipticine in suspension following oral administration at 250 mg/kg in fasted mice. In comparison to the suspension, ellipticine tissue levels were about threefold higher with polyvinylpyrrolidone or hydrochloride preparations. Antitumor activity of the three preparations was evaluated intraperitonneally and orally versus L-1210 leukemia. The optimal dose of ellipticine--polyvinylpyrrolidone and ellipticine hydrochloride was lower than that of the suspension and suggested improved absorption.
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PMID:Dissolution and absorption of the antineoplastic agent ellipticine. 64 92


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