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)

Selenium exists in a number of forms with differing valence states, some of which have shown antitumor activity. We studied the tumoricidal activity of four currently available selenium forms against a human leukemia cell line and exploited the differences among them to investigate the mechanism of antitumor action. Only selenocystine and sodium selenite showed antitumor activity, and these were also the only compounds which demonstrated significant redox chemistry, including depletion of cellular glutathione, stimulation of glutathione reductase, and stimulation of oxygen consumption. The interaction of these two compounds with glutathione suggests an intriguing potential role for them in cancer therapy.
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PMID:Selenium-induced cytotoxicity of human leukemia cells: interaction with reduced glutathione. 375 96

In the interval between the sampling of blood and analysis of the blood gas composition, the partial pressure of oxygen falls. The rate of fall depends on the temperature, initial level of partial pressure of oxygen in arterial blood, white cell and platelet count. Pseudohypoxaemia secondary to leukaemia and thrombocytosis can be recognized if the arterial blood sample is kept in ice until analysis can be carried out.
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PMID:[Pseudohypoxemia and a myeloproliferative syndrome]. 377 59

A collected series from the English literature up to 1984 of spontaneous clostridial myonecrosis (SCM) is presented in order to reveal possible common denominators. SCM was associated with malignancy (colonic cancer and leukaemia), diabetes, and injections in descending order. C. perfringens was isolated in more than 70% of the cases followed by C. septicum in 27 and C. novyi in 7%. The pathogenesis is still speculative but is thought to be due to bacteraemia especially from the gastrointestinal tract, due to growth of dormant spores in tissue following antecedent trauma or as an infection descending along the ilio-psoas sheath from a gastrointestinal focus. The symptoms are pain in an oedematous, discoloured, crepitant area with haemorhagic bullae and often shock. The diagnosis is based on the clinical findings and Gram-positive rods in the exudate. Treatment instituted promptly constitutes of surgical debridement, antibiotics and hyperbaric oxygen. The prognosis of SCM is worse than for other cases of clostridial myonecrosis and survival was in this collected series only 19%.
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PMID:Spontaneous clostridial myonecrosis. A collective review and report of a case. 382 67

The antitumor antibiotic mitomycin C (MMC) was studied in vitro using L1210 leukemia and 8226 human myeloma cells. Cytotoxicity was evaluated by colony formation in soft agar, and DNA damage was analyzed using alkaline elution filter assays. The purposes of these studies were: (a) to characterize the time course of MMC-DNA damage; (b) to characterize the type of DNA damage [DNA-DNA interstrand cross-links (ISC), DNA-protein cross-links (DPC), single and double strand breaks (SSBs, DSBs)]; and (c) to correlate this damage with cytotoxicity in vitro. Colony-forming assays showed the D0 value for 1 h MMC to be 15.0 microM for L1210 cells and 17 microM for 8226 cells. Alkaline elution studies showed that dose-dependent ISCs and DPCs formed rapidly following MMC exposure. Removal of cross-links was delayed, with only 50% repaired 32 h after exposure. There was a good correlation between ISCs and cytotoxicity in dose-response studies in each cell line. ISCs appeared to comprise most of the MMC-DNA lesions in both cell lines. No DNA SSBs or DSBs were observed following MMC exposure. Nuclei isolated from both cell lines and exposed to MMC produced less MMC alkylation than whole cells but, again, no strand breaks were evident. These results demonstrate that MMC is principally an alkylating agent when used at pharmacological (cytotoxic) concentrations in vitro. The lack of evidence for DNA strand breaks discounts a significant role for putative quinone-generated oxygen free radicals in the production of MMC cytotoxicity.
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PMID:Interactions of mitomycin C with mammalian DNA detected by alkaline elution. 392 1

Mice that had received 10(6) P388 leukemia cells IV 8 days previously exhibited a decrease in the components of the hepatic microsomal mixed function oxidase, with a 58% decrease in cytochrome P-450, and up to a 60% decrease in hepatic microsomal metabolism of biphenyl. Liver weight was increased by 49% due to infiltration of the liver with leukemic cells. Changes in liver drug-metabolizing activity and liver weight were not seen 6 days after administration of P388 leukemia. There was a small increase in serum liver enzyme but no increase in total serum bilirubin in tumor-bearing mice. In vivo total-body plasma clearance of cyclophosphamide, a drug metabolized by hepatic cytochrome P-450, was decreased to 53 ml/min/kg in mice that had received P388 cells 8 days earlier, as against 97.2 ml/min/kg in control mice. Cytochrome P-450-independent metabolism of [14C]5-fluorouracil, measured by means of [14C]CO2 in the breath over 3 h, was decreased to 21% of the dose administered by 8 days after tumor cell administration, compared with 31% of the dose in control mice. P388 leukemia cells growing in the ascitic form in the intraperitoneal cavity of mice did not release an inhibitor of 5-fluorouracil metabolism into the ascitic fluid. Total-body plasma clearance of indocyanine green was decreased to 11 ml/min/kg by 8 days after P388 cell administration, compared with 36 ml/min/kg in control mice. The decrease in indocyanine green clearance might reflect a decrease in hepatic blood flow in the tumor-bearing mice. A possible explanation for the decrease in hepatic drug metabolism caused by P388 leukemia is that the hepatocytes are deprived of oxygen and nutrients by the tumor in the liver, coupled with or caused by a physical obstruction of hepatic blood flow.
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PMID:Effects of advanced leukemia on hepatic drug-metabolizing activity in the mouse. 394 Feb 19

Mammalian erythrocytes have large amounts of catalase, an enzyme which catabolizes hydrogen peroxide (H2O2). Because catalase has a low affinity for H2O2, others have suggested that glutathione peroxidase clears most H2O2 within the erythrocyte and that catalase is of little import. We hypothesized that erythrocyte catalase might function to protect heterologous somatic cells against challenge by high levels of exogenous H2O2 (e.g., in areas of inflammation). We find that, whereas nucleated cells (L1210 murine leukemia) are readily killed by an enzymatically generated flux of superoxide (and, therefore, H2O2), the addition of human and murine erythrocytes blocks lethal damage to the target cells. Inhibition of erythrocyte superoxide dismutase, depletion of glutathione, and lysis of the erythrocytes do not diminish this protection. However, inhibition of erythrocyte catalase abrogates the protective effect and the addition of purified catalase (but not superoxide dismutase) restores it. Furthermore, erythrocytes derived from congenitally hypocatalasemic mice (in which other antioxidant systems are intact) do not protect L1210 cells. Our results raise the possibility that the erythrocyte may serve as protection against by-products of its own cargo, oxygen.
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PMID:Erythrocyte catalase. A somatic oxidant defense? 394 56

Pd(II) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric absorption, fluorescence, and circular dichroism measurements, we have shown that adriamycin can form two complexes with Pd(II). The first complex (I) involves two molecules of drug per Pd(II) ion; one of the molecules is chelated to Pd(II) through the carbonyl oxygen on C12 and the phenolate oxygen on C11, and the other one is bound to Pd(II) through the nitrogen of the amino sugar. This complexation induces a stacking of the two molecules of drug. In the second complex (II), two Pd(II) ions are bound to two molecules of drug (A1 and A2). One Pd(II) is bound to the oxygen on the carbons C11 and C12 of molecule A1 and the amino sugar of molecule A2 whereas the second Pd(II) ion is bound to the oxygen on C11 and C12 of molecule A2 and the amino sugar of molecule A1. The same complexes are formed between Pd(II) and daunorubicin. The stability constant for complex II is beta = (1.3 +/- 0.5) X 10(22). Interaction with DNA has been studied, showing that almost no modification of the complex occurred. This complex displays antitumor activity against P-388 leukemia that compares with that of the free drug. Complex II, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase.
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PMID:Metal anthracycline complexes as a new class of anthracycline derivatives. Pd(II)-adriamycin and Pd(II)-daunorubicin complexes: physicochemical characteristics and antitumor activity. 396 54

A series of quinone- and sugar-modified analogs of adriamycin have been tested for growth inhibition of adriamycin-sensitive (P388/S) and -resistant (P388/ADR) sublines of P388 murine leukemia cells in vitro. P388/ADR is less resistant to analogs of adriamycin containing either a 3'-deamino-3'-(4"-morpholinyl) group, MRA; or a -(3"-cyano-4"-morpholinyl) group, MRA-CN, than to adriamycin. However, MRA-CN was the most potent growth inhibitor of either subline. This potency is reduced by either modification of the quinone unit with a 5-imino substituent or restriction of the cyano-morpholinyl ring by an oxygen bridge to the daunosamine sugar. The calcium antagonist verapamil substantially increases the cytotoxicity of adriamycin to P388/ADR but has no appreciable effect on the cytotoxicity of either MRA or MRA-CN. The results suggest that increased uptake and retention by both MRA and MRA-CN may contribute to their increased cytotoxicity, but that the intense potency of the cyano-morpholinyl analogs must be due to other unique properties of these compounds.
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PMID:Comparative cytotoxicities of various morpholinyl anthracyclines. 397 81

4,6-Dioxoheptanoic acid (succinylacetone, SA), a potent inhibitor of heme biosynthesis, suppressed growth and decreased respiration of L1210 leukemia cells in vitro. Growth of cells incubated in the presence of 2--4 mM SA for the first 2 days declined, and after 3 days virtually ceased. L1210 cells in the logarithmic growth phase exhibited active respiration (40 +/- 9.3 nanoatoms oxygen/min X 10(7) cells at 37 degrees C) which was inhibited by and released by uncouplers of oxidative phosphorylation. These and other inhibitors of mitochondrial function clearly demonstrate a mitochondrial basis for the cellular respiration in both control and SA-treated cells. L1210 cells in the stationary phase exhibited a marked decrease in oxygen consumption compared to cells in logarithmic growth. At the concentrations used in this study, SA was not immediately toxic to L1210 cells, but inhibited growth at 2 days without lowering levels of cellular heme. Thus, it appears unlikely that inhibition of growth of L1210 cells by SA can be ascribed either to heme depletion or to impairment of respiration.
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PMID:Effects of succinylacetone on growth and respiration of L1210 leukemia cells. 399 99

Suspensions of leukemic lymphocytes and myeloblasts and blood of leukemic patients were studied to examine (a) the effect of leukemic cells on blood viscosity and (b) the ability of leukemic cells to traverse channels of capillary diameter. The viscosity of suspensions of leukemic cells was dependent logarithmically on (a) shear strain rate and (b) cytocrit, although, suspensions of small lymphocytes and of myeloblasts had a similar viscosity at equivalent shear rates and cytocrit. The minimum apparent viscosity (MAV) of leukemic cells and red blood cells, measured over shear rates of 2.3-230 s(-1) was dependent logarithmically on cytocrit. However, MAV was slightly greater for leukemic cells than for red cells at cytocrits up to 20%. At cytocrits above 20%. MAV of leukemic cells increased more rapidly than that of erythrocytes. For example, at a 15% cytocrit MAV(WBC) (1.85 centipoise) was only slightly greater than MAV(RBC) (1.59); whereas, at 45% cytocrit MAV(WBC) (14.9) was markedly greater than MAV(RBC) (3.81). The blood of subjects with leukemia with marked elevation of leukocyte concentration (leukocrits of 6-32%) had 24% higher mean MAV (3.72) than blood with a similar total cytocrit composed of red cells (3.00). A negative correlation was present between leukocrit and erythrocrit in chronic lymphocytic (r = - 0.82) and chronic granulocytic (r = - 0.81) leukemia. Therefore, the modest increase in whole blood MAV in leukemia can be explained by (a) the negative association of leukocrit and erythrocrit and (b) the rarity of leukocrits over 20% and total cytocrits over 45%. However, the MAV of blood of leukemic patients was 71% greater than expected on the basis of their packed red cell volume. Hence, the ratio of hemoglobin concentration (O(2) carrying capacity) to MAV was abnormally low in the subjects with leukemia studied. Individual leukemic leukocytes were nearly rigid. The mean deformability index (DI) of leukemic myeloblasts (1.22; 1.18) and lymphocytes (1.22; 1.40) as measured by filtration and elastometry, respectively, at 50 mm H(2)O negative pressure, approached that of a rigid body (1.0) as compared to red cells studied by filtration (3.09) or elastometry (4.23). The ability of leukemic cells to traverse nucleopore filter or micropipette channels was related to cell diameter. The relevance of the rheology of leukemic cells to the interruption of blood flow and of tissue oxygen delivery and thereby to clinical manifestations of leukemia is considered.
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PMID:Rheology of leukocytes, leukocyte suspensions, and blood in leukemia. Possible relationship to clinical manifestations. 450 37


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