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)

The acridine derivative AMSA, Amsacrine, is a new anticancer drug which was effective in patients with advanced AML and ALL in studies performed in USA. In a multicenter phase II trial we treated 27 patients with acute resistant leukemia with AMSA. All presented progressive disease following several drug combination regimens. Out of the 25 evaluable patients 5 were resistant to primary therapies, 13 were in 2nd relapse, 6 in 3rd, and 1 in 4th relapse. Dosage was 75 mg/m2, iv, day 1-7, all 3-5 weeks. On an average, only 76% of the planned dose per cycle could be given, due to severe leucopenia. From 21 patients with ALL, 1 CR and 3 PR were observed; the 3 patients with ALL presented 1 CR and 1 PR. 1 AUL showed progressive disease. In all patients a marked cell reduction could be observed in the peripheral blood. The general tolerance was good. The most important side-effect was bone-marrow toxicity, 48% (12/25) presented leucopenia less than or equal to 600/mm3, 5 (20%) had fatal septic complications. All 5 early death presented high initial leucocyte counts of greater than or equal to 32.000 mm3 as a common risk factor. In conclusion, AMSA is an effective drug in heavily pretreated patients with AML and ALL.
 ...
PMID:[Phase II study of AMSA in adults with acute therapy-refractory leukemias]. 635 48

The recently developed acridine derivative 4'-[(9-acridinyl)amino] methanesulphon-m-anisidine (m-AMSA) has become one of the preferred agents in the management of acute leukaemia but little is known of its effects on cellular immune components. We evaluated the qualitative and quantitative effects of m-AMSA on immune cell numbers and function, during both the leucopenic and myelorestorative phases, following intermittent high-dose therapy. Cell-mediated and inflammatory responses were depressed in the treated animals during the leucopenic phase but restoration of immune capability paralleled the recovery of circulating leucocyte numbers. Additionally, m-AMSA displayed unexpected immunomodulatory features: thymus-dependent antibody and delayed-type hypersensitivity responses were actually increased, suggesting the potential of m-AMSA as an immunoregulator in clinical and experimental studies.
 ...
PMID:Quantitative and qualitative effects of m-AMSA (amsacrine) on cellular immune components. 638 83

Eleven patients with acute leukemia, refractory to all previous chemotherapy, were treated with acridinyl anisidide (m-AMSA). Seven patients received m-AMSA i.v. as a single agent at 150 mg/m2 daily for 4 to 7 days, and 4 patients received m-AMSA at 90 mg/m2 daily for 3 days in combination with thioguanine and cytosine arabinoside. Four of the nine patients with acute nonlymphoblastic leukemia responded to the treatment, and complete remission was obtained in three of them. One of these patients remained in complete remission 5 months after therapy. Three of the four responding patients received m-AMSA as a single agent. Two patients with resistant acute lymphoblastic leukemia did not respond. As in earlier trials with m-AMSA reported by others, about one-third of our refractory patients responded, which justifies the future use of this agent in refractory leukemia and in other regimens for the induction of remission in acute leukemia. Despite minimal cardiotoxicity of the drug, evidence of its cardiotoxic potential is recorded.
 ...
PMID:Acridinyl anisidide (m-AMSA) therapy in 11 patients with refractory acute leukemia. 654 40

4'-(9-Acridinylamino)-methanesulfon-m-anisidide (m-AMSA) is an acridine compound that has been found useful in the systemic treatment of acute leukemia. This paper specifically investigates the CSF pharmacokinetics of m-AMSA following both intravenous and intraventricular administration in a subhuman primate model. Following intravenous administration, m-AMSA crossed the blood-brain barrier poorly; cerebrospinal fluid (CSF) concentrations were only 1-3% of systemic concentrations. Intraventricular administration of drug achieved high initial ventricular fluid concentrations, but the drug was rapidly cleared with a half-life of 115 min. Following 500 micrograms of intraventricular drug, CSF concentrations of m-AMSA remained above 1 microM for only 6 h. These data suggest that m-AMSA has potential as an intrathecal agent against meningeal leukemia refractory to more conventional therapy, but detailed toxicology and neurohistopathology will be required before intra-CSF m-AMSA can be considered for human use.
 ...
PMID:Intrathecally administered m-AMSA in the rhesus monkey. 654 72

Remission rates for patients with acute promyelocytic leukemia (APL) have improved with the use of anthracyclines and proper management of disseminated intravascular coagulopathy. In a prospective randomized trial of chemotherapy in patients with acute nonlymphoblastic leukemia, there were 16 patients with APL. All 7 of the patients receiving the amsacrine-containing regimen and 5 of 9 receiving the daunorubicin-containing regimen achieved a remission. All patients, except 2 of the 3 who underwent bone marrow transplantation, remain alive and in remission from 1+ to 25+ mo. Amsacrine is an effective replacement for daunorubicin in the treatment of APL, and its use does not compromise the favorable remission duration characteristic of APL.
 ...
PMID:Primary therapy of acute promyelocytic leukemia: results of amsacrine- and daunorubicin-based therapy. 658 Sep 26

Kinetics of transport of the acridine derivative 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA) were examined in P388 murine leukemia cells and in P388/ADR, a subline selected for adriamycin resistance and cross-resistant to a variety of drugs including m-AMSA. Compared with the drug-responsive parent cell line, P388/ADR cells showed impaired accumulation of m-AMSA and an enhanced rate of drug exodus. Competition studies demonstrated structural specificity of the outward transport process. There was a low degree of intracellular m-AMSA binding, and steady-state drug levels were reached in less than 1 min. These results suggest that m-AMSA will be a useful probe for studying transport systems associated with anthracycline resistance.
 ...
PMID:m-AMSA as a probe for transport phenomena associated with anthracycline resistance. 658 5

m-AMSA, an acridine dye derivative, has been utilized in 36 patients with advanced hematologic malignancies. In 22 patients with lymphoma receiving 120 mg/m2 every 3 weeks, 10(45%) have achieved remissions. Eight of these remissions have been partial. The median duration of remission in patients with lymphoma was 3 months (range 1-12+ months). In 11 patients with acute leukemia receiving m-AMSA, 40 mg/m2 t.i.d. for 5 days, three (27%) have achieved remissions. Two of the three remissions have been complete. All three remissions in patients with leukemia were sustained for 1 month. Two patients with myeloma and one patient with chronic lymphocytic leukemia failed to respond. The major toxicity of m-AMSA has been myelosuppression. The dose-limiting toxic effect in patients with lymphoma was neutropenia. Nausea and vomiting, alopecia, phlebitis, and hepatic dysfunction have been noted in a minority of patients. Phlebitis appeared to be prevented with heparin administration after m-AMSA infusion. One fatal arrhythmia occurred, apparently related to therapy. m-AMSA appears active in advanced leukemia and lymphoma. Further studies are merited, particularly in combination with known effective agents, in order to improve upon remission duration.
 ...
PMID:m-AMSA: phase II trial in advanced lymphoma and leukemia. 658 46

The ECG effect of amsacrine (m-AMSA) was evaluated in 12 consecutive patients with leukemia. m-AMSA induced a significant prolongation of the Q-T interval (msecs, mean +/- SE) before (448 +/- 13) and 1 hour after (512 +/- 12) treatment (P . 0.0001, paired t test), without concomitant changes in the P-R interval, QRS duration, and heart rate. This selective cardiotoxic effect appeared to be transient and was noted towards the end of the iv drug administration, but was not present 24 hours later. No cardiac arrhythmias were noted during continuous monitoring. Nevertheless, it is assumed that the prolongation of the Q-T interval may represent a state of increased vulnerability to rhythm disturbances. Special care should be taken to avoid factors that may prolong the Q-T interval (hypokalemia, ischemia, or premedication with phenothiazine) during the administration of m-AMSA.
 ...
PMID:Acute electrocardiographic changes induced by amsacrine. 659 38

The synthesis and biological evaluation of a series of 3-substituted 5-carboxamido derivatives of amsacrine (m-AMSA) are described. This series was developed as the result of previous quantitative structure-activity relationship (QSAR) studies of the antitumor activity of 9-anilinoacridine derivatives. In agreement with these studies, this class of compounds, possessing a variety of small nonpolar groups at the 3-position, together with very hydrophilic carboxamido groups at the 5-position, have high in vivo activity against animal leukemia models.
 ...
PMID:Potential antitumor agents. 38. 3-substituted 5-carboxamido derivatives of amsacrine. 668 29

A series of acridine monosubstituted derivatives of the antitumour agent amsacrine [4'-(9-acridinylamino)methanesulphon-m-anisidide] has been tested for activity against intraperitoneally inoculated P388 leukaemia and intravenously inoculated Lewis lung carcinoma growing in DBA/2J X C57BL/6J mice, and treated using a q4d X 3 intraperitoneal injection schedule. Whereas all derivatives tested exhibited moderate to high activity towards the leukaemia, activity against the lung tumour varied from inactive to curative. Amsacrine itself displayed low but statistically significant activity. Cyclophosphamide and 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) were highly active. 5-Fluorouracil was active but doxorubicin, daunorubicin, ametantrone and mitoxantrone showed no significant activity. Since the Lewis lung carcinoma is responsive to a high proportion of agents active against solid tumours in the clinic, it is concluded that some derivatives of amsacrine could be considerably more active than amsacrine itself against human solid tumours.
 ...
PMID:Divergent activity of derivatives of amsacrine (m-AMSA) towards Lewis lung carcinoma and P388 leukaemia in mice. 668 94


<< Previous 1 2 3 4 5 6 7 8 9 Next >>