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)

Acute myelogenous leukemia (AML) of the inbred Wistar/Furth (W/Fu) rat is pathophysiologically similar to human AML. Subcutaneous transplantation of 1.0 X 10(6) cells of a clonal tissue culture line of W/Fu AML into 6- to 8-week-old rats produced local myeloblastomas in 8--10 days which progressed to infiltration of regional nodes, replacement of greater than 90% of the bone marrow, ascites, and fatal peripheral blood leukemia with concomitant hyperlysozymemia. Single doses of adriamycin, daunomycin, actinomycin, cytosine arabinoside, or Cytoxan in rats with 1.0 cm myeloblastomas produced complete tumor regression while bu-sulfan, vinblastine, vincristine, dexamethasone, and Methotrexate was relatively ineffective. Responses were associated with delay in progression to peripheral blood leukemia and prolonged survival. Similar results were obtained following treatment of rats with already disseminated leukemia. The demonstration of response to drugs known active against human AML indicates that the W/Fu AML should be a valuable model for rapid evaluation of new chemotherapeutic agents for clinical use.
 ...
PMID:Chemotherapeutic remissions in Wistar Furth rat acute myelogenous leukemia: a model for human AML. 6 30

Methotrexate analogues, in which an additional nitrogen atom is inserted between the phenyl ring and the carbonyl group of the side chain, were prepared by photochemical methods. The compounds were less inhibitory toward dihydrofolate reductase and thymidylate synthetase derived from Lactobacillus casei than was methotrexate. They were also less cytotoxic against human lymphoblastic leukemia cells (CCRF-CEM). In vivo against L-1210 leukemia in mice, the aza homologue of methotrexate showed significant antitumor activity (%ILS = 55%) compared to methotrexate (%ILS = 88%).
 ...
PMID:Methotrexate analogues. 12. Synthesis and biological properties of some aza homologues. 10 16

Methotrexate (MTX) inhibition of the growth of mouse or human leukemia cells in culture was partially prevented by either thymidine (dThd) or hypoxanthine. 5-Fluoro-2'-deoxyuridine (FdUrd) also decreased the growth-inhibitory potency of MTX in the presence of small concentrations of 5-formyltetrahydrofolate (citrovorum factor) and sufficient exogenous dThd to support the synthesis of thymidylate nucleotides by salvage mechanisms. In addition, citrovorum factor-induced reversal of MTX was several orders of magnitude more efficient in the presence of both FdUrd and dThd than in the presence of dThd alone or in the absence of both nucleosides. Likewise, the presence of FdUrd (3 microM) and dThd (5.6 microM) completely prevented the lethality of 0.3 mM MTX to L1210 cells in culture medium supplemented with micromolar concentrations of citrovorum factor. We propose that this protection against the cytotoxic effects of MTX by dThd, hypoxanthine, and FdUrd have a common biochemical mechanism--namely, inhibition of the de novo synthesis of thymidylate by either a direct [FdUrd; inhibition of thymidylate synthetase (thymidylate synthase; 5,10-methylenetetrahydrofolate:dUMP C-methyl-transferase, EC 2.1.1.45)] or indirect (dThd and hypoxanthine; feedback inhibition by anabolites on ribonucleotide reductase and deoxycytidylate deaminase) effect. The resultant decreased rate of loss of reduced folates due to de novo thymidylate synthesis would allow a higher degree of inhibition of dihydrofolate reductase to be endured without damage to the cell.
 ...
PMID:Role of thymidylate synthetase activity in development of methotrexate cytotoxicity. 16 May 58

The antileukemic activity of cis-diamminedichloroplatinum (PDD) was studied in rats bearing myelogenous leukemia RBA-Le. Clinical picture, changes in life-span, hematological indices and weight changes were used to assess the effectiveness of the therapy. Maximum effectiveness was noted when PDD was given in combination with Methotrexate (MTX) and Poly I:C, respectively. The mean life-span of the rats treated with PDD and MTX was prolonged to 37 days that is an increase of 147 percent of the control level. Furthermore 20 percent of the treated animals survived symptom-free for more than 60 days. Out of 20 animals receiving PDD in combination with Poly I:C 6 rats survived 60 days symptom-free. In remaining 14 animals who finally died on leukemia an 85 percent increase in life-span was noted. Only slight increase in life-span was recorded in those groups treated with PDD alone and in combination with Cyclophosphamide regardless of dosage schedule. The general toxicity of PDD therapy is discussed.
 ...
PMID:Experimental chemotherapy of rat leukemia RBA-Le with cis-diamminedichloroplatinum. 27 Jun 16

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.
 ...
PMID:Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate. 27 87

Nineteen children in primary remission of acute lymphocytic leukemia (ALL) were investigated by computed tomographic (CT) scans of the brain 2 to 64 (mean 19) months after the central nervous system (CNS) prophylaxis was finished. The CNS prophylaxis consisted of high dose Methotrexate (HDM) intravenously combined with 6--8 doses of Methotrexate intrathecally. Two children received only Methotrexate intrathecally as CNS prophylaxis. In addition three children with ALL who had CNS leukemia were investigated by CT scans of the brain. Only one abnormal CT scan was found among the nineteen asymptomatic children, and one of the three patients with CNS relapse had slightly dilatated subarachnoidal spaces. These results compared with other reports in literature in which the CNS prophylaxis has consisted of intrathecal Methotrexate and cranial irradiation, suggest that there are fewer abnormal CT findings of the brain in patients not receiving cranial irradiation as part of CNS prophylaxis.
 ...
PMID:Computed tomographic findings of the brain in children with acute lymphocytic leukemia after central nervous system prophylaxis without cranial irradiation. 29 73

The important advances made in recent years in the therapy of adult ALL have been reviewed. The definition of bad-prognosis patients has been improved and includes those with T-ALL, ABLL, and Ph1+ALL, in addition to those presenting with evidence of extensive disease. In contrast to childhood ALL, induction chemotherapy should include another drug (or drugs) in addition to VCR and prednisolone, and one of the anthracycline drugs (ADR or DNR) has been employed most frequently in this context. Such therapy should result in a CR rate of 70 to 75%. Similar to the experience in childhood ALL, the improvement in haematological response rate has led to an apparent increase in CNS leukaemia, and the need for adequate CNS prophylaxis is stressed. Despite these improvements, the outlook for adults with ALL is not yet as good as it is for childhood ALL. Controlled studies involving large numbers of patients are urgently needed to provide answers to a number of questions. In induction therapy, the use of higher drug dosage, the use of more and other drugs, and the use of an individual patient's risk factors to determine drug dosage, must be assessed. The benefits of consolidation therapy and the optimal duration and intensity of maintenance therapy have yet to be established. Methods of CNS prophylaxis other than cranial irradiation and IT MTX must be carefully studied. These important questions require that adult patients with ALL should be concentrated in centres capable of providing optimal overall care and, at the same time, able to conduct the necessary clinical trials.
 ...
PMID:The management of adult acute lymphoblastic leukaemia. 36 95

A 3-year-old child diagnosed as having acute lymphatic leukemia (ALL), developed meningeal leukemia 36 months after the onset of the disease. He was twice subjected to cranial irradiation plus intrathecal methotrexate (i.t. MTX). Skull radiology showed bilateral gyriform calcification of both cerebral hemispheres. Hematological relapse was first detected 5 years after diagnosis and the child died 5 months later. The most striking findings of a right frontal lobe biopsy and the postmortem examination were wide calcium deposits located in the cortex and in the adjacent white matter. Intense demyelination as well as areas of neuron poverty were apparent in the necropsy but in the biopsy specimen. The possible interrelationship between such deposition and cranial irradiation and/or i.t. MTX suggests a new iatrogenic disorder.
 ...
PMID:Intracerebral calcifications in childhood lymphoblastic leukemia. A new iatrogenic disease? 41 41

Exposure of L1210 leukemia cells first to 0.1 to 100 micromolar methotrexate and then to 10 micromolar 5-fluorouracil produces a synergistic effect on the number of cells killed in culture. Methotrexate dose-related increases occur in the concentrations of intracellular 5-fluorouracil ribonucleotides and 5-fluoro-2'-deoxyuridylate and in the incorporation of 5-fluorouracil into RNA. These increases are correlated with increased concentrations of intracellular phosphoribosylpyrophosphate. It is proposed that the enhanced formation of ribonucleotides of 5-fluorouracil and the subsequent incorporation of these compounds into RNA in methotrexate-treated cells may account for synergism between these agents.
 ...
PMID:Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism. 47 32

We have reviewed the neurological complications not directly attributable to leukaemic infiltration in a group of 438 children with leukaemia or lymphoma. 61 children had one or more complications due chiefly to bleeding, infection, or drug toxicity. Early death from intracranial haemorrhage occurred in 1% of children with lymphoblastic leukaemia and 7% of children with myeloblastic leukaemia. Measles and chicken pox were the most serious infective complications; one child remains severely retarded after presumed measles encephalitis, one child with chicken pox died, and a second remains disabled. 2 additional cases of measles encephalitis and one of progressive multifocal leucoencephalopathy are described. Drugs which caused neurotoxicity included vincristine, cytosine arabinoside, L-asparaginase, and phenothiazines, but most problems were caused by methotrexate. Methotrexate toxicity was more prevalent and more serious in children who had had previous central nervous system leukaemia. We conclude that viral infections and methotrexate pose the greatest neurological hazards to children with leukaemia.
 ...
PMID:Neurological complications of childhood leukaemia. 59 22


1 2 3 4 5 6 7 8 9 10 Next >>