Search results for "Amsacrine"
showing 10 items of 10 documents
Amsacrine with high-dose cytarabine is highly effective therapy for refractory and relapsed acute lymphoblastic leukemia in adults
1988
Abstract Thirty-six patients with relapsed acute lymphoblastic leukemia (ALL) and four with primary refractory ALL were treated with a regimen that included amsacrine, 200 mg/m2, intravenously daily for three days with cytarabine, 3 gm/m2, by infusion over three hours daily for five days. There were 27 remissions in the 36 relapsed patients and two in the four patients with primary refractory disease. Seventeen of the 23 patients with common ALL, four of the six with T-cell ALL, one of the three with B-cell ALL, and seven of eight whose cells were not characterized responded. Toxicity of this regimen was comparable to other reinduction regimens for ALL, but the side effects characteristic o…
Apoptotic effects of different drugs on cultured retinoblastoma Y79 cells
1998
This paper deals with the apoptotic effect exerted in human retinoblastoma Y79 cells by a number of compounds. A remarkable effect was observed after treatment with DNA-damaging agents, such as camptothecin, etoposide, cisplatin and carboplatin; camptothecin was found to be the most efficacious. Treatment with these compounds induced the appearance of morphological features of apoptosis in the cells together with the distinct fragmentation of DNA, as shown by agarose gel electrophoresis. These effects were also accompanied by a remarkable increase in the level of p53. Many other compounds, which are not DNA-damaging agents, induced the morphological features of apoptosis but none of them we…
Induction of apoptosis in human retinoblastoma cells by topoisomerase inhibitors
1998
PURPOSE:To examine the apoptotic effect induced in human retinoblastoma Y79 cells by camptothecin, etoposide, and amsacrine, to examine the effect of these drugs on the expression of many apoptosis-related modulators, and to test the antiapoptotic effect exerted by insulin-like growth factor-I (IGF-I). METHODS:Morphologic features of apoptosis were demonstrated using acridine orange- ethidium bromide staining and electron microscopy. DNA fragmentation was determined by means of an in situ cell detection procedure (TdT-dUTP terminal nick-end labeling [TUNEL]) or by electrophoresis on agarose gels and was quantified by enzyme-linked immunosorbent assay. The expression of apoptosis-related mod…
Identification of conjugation and cleavage products in the thiolytic metabolism of the anticancer drug 4'-(9-acridinylamino)methanesulfon-m-anisidide.
1981
Conjugation and cleavage products in the thiolytic metabolism of the anticancer drug 4′ -(9-acridinyl amino)methanesulfon-m-anisidide were identified primarily by high-pressure liquid chromatography in combination with field desorption mass spectrometry. The spontaneous metabolic pathway of the drug, as related to its susceptibility to nucleophilic attack by endogenous thiols at the 9-carbon atom of the acridine moiety, has been studied. Among the metabolite fraction of 4′-(9-acridinylamino)methanesulfon-m-anisidide excreted in rat bile after administration of a therapeutic dose, a conjugate was identified as the 9-acridinyl thioether of glutathione. This conjugation product and the corresp…
Chemotherapy with Idarubicin, Ara-C,VP-16, Amsacrine, Followed by G-CSF and Maintenance Immunotherapy with Interleukin-2 for Patients with High-Risk …
1998
To improve the complete remission (CR) rate and to prolong CR duration in patients with advanced MDS, AML evolving from MDS, and secondary AML, a phase-III trial of aggressive chemotherapy followed by G-CSF was initiated in January 1992. Pts. achieving a CR were randomized to receive either high-dose or low-dose IL-2 to evaluate the potential of this cytokine to eliminate residual leukemic cells and to prolong the CR duration.
Development and Partial Characterization of a Human T-Lymphoblastic Leukemic (CCRF-CEM) Cell Line Resistant to Etoposide. Analysis of Possible Circum…
1996
We have selected an etoposide-resistant variant (CCRF-CEM/VP-16) of the human T-lymphoblastic CCRF-CEM leukemia for study. Resistance to the topoisomerase II (topo II) inhibitor was about 11-fold and stable. Other data revealed that the new cell line had acquired an atypical, non-P-glycoprotein overexpressing multidrug resistant (MDR) phenotype with cross-resistance to other topo II inhibitors (amsacrine, doxorubicin, and mitoxantrone) and to glucocorticoids, but not to novobiocin, ICRF-187, vincristine or cisplatin. In a first instance, we assumed that altered drug-topo II interactions, based on quantitative and/or qualitative modifications of the enzyme, are a cause of resistance in the c…
Quinoline anticancer agents active on DNA and DNA-interacting proteins: From classical to emerging therapeutic targets.
2021
Quinoline is one of the most important and versatile nitrogen heterocycles embodied in several biologically active molecules. Within the numerous quinolines developed as antiproliferative agents, this review is focused on compounds interfering with DNA structure or with proteins/enzymes involved in the regulation of double helix functional processes. In this light, a special focus is given to the quinoline compounds, acting with classical/well-known mechanisms of action (DNA intercalators or Topoisomerase inhibitors). In particular, the quinoline drugs amsacrine and camptothecin (CPT) have been studied as key lead compounds for the development of new agents with improved PK and tolerability…
Effects of amsacrine (m-AMSA), a new aminoacridine antitumor drug, on the rabbit heart.
1983
There is emerging clinical evidence that amsacrine (m-AMSA) administration may be associated with cardiotoxic effects such as severe, even fatal, ventricular arrhythmias and impairment of the inotropic performance of the heart. Information on the cardiac effects of m-AMSA in animals is scanty. Studies on mice, dogs, and monkeys have not evidenced the cardiotoxicity of the compound. The data presented in this paper show that m-AMSA causes acute ECG alterations in normal rabbits and a dose-related negative inotropic effect on the isolated rabbit heart, suggesting that this species may be a useful model for the study of the cardiac actions of this antiblastic.
Field desorption mass spectrometric characterization of thiol conjugates related to the oxidative metabolism of the anticancer drug 4′-(9-acridinylam…
1983
Conjugation products with glutathione (GSH) and other endogenous thiol derivatives related to the oxidative metabolism of the anticancer drug, 4′-(9-acridinlyamino) methanesulfon-m-anisidide (m-AMSA) were synthesized and characterized by field desorption mass spectrometry. The primary microsomal oxidation product of m-AMSA, m-AQDI, was prepared by MnO2 oxidation of the parent drug and reacted with equimolar GSH, cysteine, N-acetylcysteine and N-acetylcysteine methyl ester to form m-AMSA-(5′)-thiol conjugates linkedat the aniline ring, as major products. Field desorption mass spectra of the conjugates provided abundant [MH]plus; ions, and characteristic fragment ions by cleavage at the thioe…
The DNA topoisomerase II catalytic inhibitor merbarone is genotoxic and induces endoreduplication
2012
Abstract In the last years a number of reports have shown that the so-called topoisomerase II (topo II) catalytic inhibitors are able to induce DNA and chromosome damage, an unexpected result taking into account that they do not stabilize topo II-DNA cleavable complexes, a feature of topo II poisons such as etoposide and amsacrine. Merbarone inhibits the catalytic activity of topo II by blocking DNA cleavage by the enzyme. While it was first reported that merbarone does not induce genotoxic effects in mammalian cells, this has been challenged by reports showing that the topo II inhibitor induces efficiently chromosome and DNA damage, and the question as to a possible behavior as a topo II p…