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)

Previous papers in this series have described efficient syntheses of 3'-O-acyl and 3',5'-di-O-acyl and 3',5'-di-O-acyl derivatives of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine hydrochloride (1,3). It has now been shown that the 2,2'-anhydro linkage in 1 and 3 can be selectively and efficiently cleaved by treatment with a mixture of pyridine and methanol giving the corresponding 3'-O-acyl derivatives of 1-beta-D-arabinofuranosylcytosine (2,4). The selective hydrolysis of the more soluble derivatives can also be achieved using either aqueous pyridine or a mixture of sodium carbonate and sodium bicarbonate in aqueous dioxane. Using the above procedures 3'-O-acyl araCs and 3',5'-di-O-acyl araCs with saturated or unsaturated ester groups containg from 2 to 22 carbon atoms have been prepared, and these substances have been evaluated for cytotoxicity and antiviral activity in tissue culture and for antitumor activity these substances have been evaluated for cytotoxicity and antiviral activity in tissue culture and for antitumor activity against L1210 leukemia in mice. Many of the compounds show high anti-L1210 activity relative to araC itself.
 ...
PMID:Reactions of 2-acyloxyisobutyryl halides with nucleosides. Synthesis and biological evaluation of some 3"-acyl and 3',5'-diacyl derivatives of 1-beta-D-arabinofuranosylcytosine. 17 73

In RBL-2H3 rat basophilic leukemia cells, Ca2+ influx and secretion are activated by antigens that crosslink IgE-receptor complexes and by the Ca2+ ionophore, ionomycin. Here we report that antigen-stimulated Ca2+ influx and secretion are impaired and ionomycin-induced responses are strongly inhibited following the removal of HCO3- from the medium. These results raised the possibility that HCO3(-)-dependent pH regulation mechanisms play a role in the cascade of events leading to mast cell activation. To test this hypothesis, intracellular pH (pHi) was measured by ratio imaging microscopy in individual RBL-2H3 cells labeled with 2',7'-bis-(2-carboxyethyl)-5-(6) carboxyfluorescein (BCECF). In unstimulated cells, it was found that basal pHi in the presence of HCO3- is 7.26, significantly greater than pHi in its absence, 7.09 (P less than 10(-6]. These results, as well as evidence that pHi increases rapidly when HCO3- is added to cells initially incubated in HCO3(-)-free medium, indicate that unstimulated cells use a HCO3(-)-dependent mechanism to maintain cytoplasmic pH. Further analyses comparing unstimulated with stimulated cells showed that antigen causes a small transient acidification in medium containing HCO3- and a larger sustained acidification in HCO3(-)-depleted medium. Ionomycin is a more potent acidifying agent, stimulating a sustained acidification in complete medium and causing further acidification in HCO3(-)-free medium. These results support the hypothesis that the inhibition of antigen- and ionomycin-induced 45Ca2+ influx and secretion in cells incubated in HCO3(-)-free medium is at least partially due to the inactivation of HCO3(-)-dependent mechanisms required to maintain pH in unstimulated cells and to permit pH recovery from stimulus-induced acidification.
 ...
PMID:Importance of bicarbonate ion for intracellular pH regulation in antigen- and ionomycin-stimulated RBL-2H3 mast cells. 154 61

A series of ellipticine glycosides [2-N-glycosyl quaternary pyridinium salts of three ellipticines: ellipticine (1), 9-methoxyellipticine (2), and 9-hydroxyellipticine (4)] were stereoselectively synthesized in good yields by an improved condensation reaction between ellipticines [1, 2, and 9-acetoxyellipticine (3)] and protected (peracylated and perbenzylated) glycosyl halides with cadmium carbonate, followed by deprotection. These glycosides were preliminarily evaluated for their antitumor activity in the L1210 leukemia system. Twenty-six (53%) of the 49 glycosides tested were curative, and five [9-hydroxyellipticine L-arabinopyranoside (41b), D-lyxofuranoside (43a), L-lyxopyranoside (44b), D-xylofuranoside (49a), and L-rhamnopyranoside (56)] were selected for extended evaluation on the basis of their high levels of activity. The structure-activity relationships are discussed. The selected glycosides showed remarkable activity in six different murine tumor systems with excellent therapeutic ratios; their efficacy surpassed that of doxorubicin against three of these systems. On the basis of these results and ease of formulation, the two glycosides 41b (SUN4599) and 49a (SUN5073) were selected for further preclinical evaluation and possible clinical development.
 ...
PMID:Synthesis and antitumor activity of quaternary ellipticine glycosides, a series of novel and highly active antitumor agents. 338 25

On the consideration that the highly active DNA-nonbinding adriamycin analogues N-(trifluoroacetyl)adriamycin 14-valerate and N-(trifluoroacetyl)adriamycin 14-O-hemiadipate undergo initial metabolic conversion to N-(trifluoroacetyl)adriamycin by the action of nonspecific serum and tissue esterases, a number of N-(trifluoroacetyl)adriamycin 14-thio esters have been prepared and studied for in vitro growth inhibition, vs. human-derived CCRF-CEM leukemic lymphocytes, and in vivo antitumor activity, vs. murine P388 leukemia, relative to the rate of thio ester deacylation induced by esterases present in mouse serum. Products were obtained by reaction of N-(trifluoroacetyl)-14-bromodaunorubicin with thioacetic, thiopropionic, thiobutyric, thiovaleric, and thiobenzoic acids in ethanol, in the presence of potassium carbonate. Because little is known about similar thio ester derivatives of adriamycin itself, the corresponding adriamycin 14-thio esters were also prepared and evaluated for antitumor activity; with these products, determination of their extent of interaction with calf thymus DNA was also performed. For the adriamycin thio ester products, significant in vivo anti-P388 activity was seen with the thioacetate, thiovalerate, and thiobenzoate derivatives, although no compound matched the curative effects of N-(trifluoroacetyl)adriamycin 14-valerate in this system. With respect to the N-(trifluoroacetyl)adriamycin 14-thio ester products, although the corresponding oxo ester analogues are all significantly biologically active, none of the thio ester derivatives showed activity in vitro or in vivo.
 ...
PMID:Adriamycin analogues. Preparation and biological evaluation of some thio ester analogues of adriamycin and N-(trifluoroacetyl)adriamycin 14-valerate. 380 75

A 38-year-old woman developed chronic myeloid leukaemia after 2 years of lithium carbonate therapy. A peculiar feature of her leukaemia, as well as of the 5 patients previously reported in whom CML has developed in the course of lithium therapy, was the unusually high degree of granulocyte maturation manifested in normal leucocyte alkaline phosphatase (LAP) score and, in 1 case, selective increase of transcobalamin III. Although a cause and effect relation between lithium therapy and CML has not yet been established, in view of the stimulatory effect of lithium on granulocyte proliferation, such treatment should be avoided in patients with established myeloproliferative disorders, or in patients at high risk of developing leukaemia.
 ...
PMID:Increased leucocyte alkaline phosphatase and transcobalamin III in chronic myeloid leukaemia associated with lithium therapy. 385 3

The authors report a case of acute myeloid leukemia in a thirty-four-year-old man who had been under lithium carbonate for the last six months for manic-depressive psychosis. One year after treatment with cytosine-arabinoside, 6-thioguanine and daunorubicin, the patient is still in complete remission. In the medical literature we found seven additional reports of acute or chronic myeloid leukemia after lithium therapy. Lithium was found to enhance granulopoiesis. Our findings suggest that lithium may initiate or promote leukemia.
 ...
PMID:[Lithium and acute myeloid leukemia]. 630 3

In a two-layer soft agar system the indirect effect of lithium via colony stimulating factor and/or its direct effect on the granulocyte progenitor cells of bone marrow of healthy volunteers, patients with different hematological disorders, and with small-cell carcinoma of the lung, were evaluated. A significant increase in the number of myeloid colonies was found with a concentration of 0.1 mmol/l lithium carbonate in the feeder layer in all patient groups except those with overt acute myelomonocytic leukemia (AMMoL). No effect was seen if lithium was added to the overlayer. The increment of colonies cultured with lithium in the feeder layer was directly related to the initial number of colonies cultured without lithium (correlation coefficient 0.96). The former colonies had a 1.5- to 2-times larger size than the latter, and cell cycle analysis showed a significant increase in the percentage of cells in S, G2 and M phase. No such effects were seen in AMMoL on the number and size of the colonies and the characteristic growth pattern. In this study lithium has an indirect effect on the number and size of bone marrow myeloid colony formation in healthy people as well as patients with different hematologic cell disorders and small-cell carcinoma of the lung, while no such influence was observed with overt AMMoL patients.
 ...
PMID:In vitro effects of lithium on granulocyte colony formation in normal men, in hematological disorders and in small-cell carcinoma of the lung. 630 77

A case of hairy cell leukaemia complicated as a terminal event by massive retroperitoneal lymphadenopathy is described. The patient had recently been treated with lithium carbonate and had previously been demonstrated to suffer from a systemic vasculitis, either or both of which may have contributed to the development of this rare complication.
 ...
PMID:Massive retroperitoneal lymphadenopathy as a terminal event in hairy cell leukaemia. 636 Apr 96

Effects of lithium carbonate on peripheral white blood cell and granulocyte counts were investigated in children treated for acute lymphoblastic leukaemia and non-Hodgkin malignant lymphoma. Li2CO3 given orally for two weeks in a single daily dose of 700 mg/m2 caused a significant and lasting increase in the peripheral WBC and granulocyte counts and increased the granulocyte ratio during induction of remission and maintenance cytotoxic therapy. Haematologic actions and the long-term effect of lithium carbonate are discussed.
 ...
PMID:Effect of lithium carbonate on the peripheral leukocyte count in children suffering from haematological malignancies. 641 73

Lipophilic methotrexate (MTX) and 3',5'-dichloromethotrexate (DCM) diesters were prepared by HCl-catalyzed esterification or by neutral esterification using cesium carbonate and an alkyl or aralkyl halide in Me2SO. The products were tested for in vivo antitumor activity against L1210 leukemia in mice to test whether all MTX and DCM diesters are therapeutically equivalent in this species. Contrary to what has been found with simple primary dialkyl esters, ortho-substituted dibenzyl esters of MTX produce longer survival on a q3dX3 schedule than does MTX itself and show a dose-sparing effect comparable to that of MTX at shorter treatment intervals. Thus, MTX bis(6-chloropiperonyl) ester at an MTX-equivalent dose of 5.5 mg/kg gave a +88% increase in median life span (ILS), whereas for MTX a +88% ILS required 30 mg/kg. When the MTX-equivalent dose of MTX bis(6-chloropiperonyl) ester was increased to 40 mg/kg, a +167% ILS was observed, as compared with a +100% ILS with 60 mg/kg of the parent drug. High activity (greater than 100% ILS) was likewise shown by the bis(2,5-dimethylbenzyl), bis(2,6-dichlorobenzyl), and di-3-picolyl esters of MTX and by the bis(1-methylbutyl) ester of DCM. The results of this study indicate that MTX and DCM esters are not therapeutically equivalent in mice, despite the high serum esterase activity in this species, and that an up to 10-fold reduction in total administered dose on the q3dX3 schedule is feasible by this approach.
 ...
PMID:Methotrexate analogues. 18. Enhancement of the antitumor effect of methotrexate and 3',5'-dichloromethotrexate by the use of lipid-soluble diesters. 662 Mar 3


1 2 3 4 Next >>