Disease relevance of AMSA

• Ventricular fibrillation, hypokalemia, and AMSA therapy [1].
• Thirty previously treated adults with lymphoma received AMSA as single agent therapy [2].
• The response rate to AMSA was found to correlate with the type of response to frontline therapy and also with the number of previous relapses [2].
• The side effects associated with AMSA therapy included mild nausea and vomiting, stomatitis, diarrhea, phlebitis, alopecia, and myelosuppression-related infections [3].
• Initial experience with AMSA as single agent treatment against malignant lymphoproliferative disorders [2].

High impact information on AMSA

• Murine P388 (P) leukemia cell lines resistant to amsacrine (P/AMSA), dactinomycin (P/DACT), and doxorubicin (P/DOX) were compared with the parental strain in their sensitivity to a number of derivatives of amsacrine [4].
• CEM/VM-1, CEM/VM-1-5, and HL-60/AMSA human leukemic cell lines were used as controls; 3 of 3 known mutations were detected by migration differences of polymerase chain reaction products from the RNA extracted from these three lines [5].
• Thus far, the HL-60/AMSA genotype has not been identified in the cells from any individual, suggesting that this genotype is indeed a mutation and not an allelic form of topoisomerase II [6].
• Efficacy and clinical cross-resistance of a new combination therapy (AMSA/VP16) in previously treated patients with acute nonlymphocytic leukemia [7].
• No base-pair specificity could be confirmed; however, a high affinity of AMSA to poly(A) chains was demonstrated [8].

Chemical compound and disease context of AMSA

• Phase II study of AMSA and doxorubicin to treat metastatic breast cancer [9].
• Severe neutropenia of less than 500 granulocytes/microliter was observed in 5 pts in the AMSA group compared with 13 pts in the AMSA + DTIC group [10].
• We measured the effect of 6 standard (Adriamycin, BCNU, DTIC, melphalan, vinblastine, actinomycin D) and 3 Phase II agents (cis-platinum, vindesine, AMSA) on melanoma colony-forming units (CFU) in soft agar from biopsies of 50 patients with metastatic melanoma [11].
• Pilot studies to obtain drug dosages for the combinations of dibromodulcitol (DBD) and BP-16, DBD and AMSA, and DBD, VP-16 and AMSA were carried out to levels of acceptable clinical toxicity [12].
• Frameshift mutagenesis by 9-aminoacridine, ICR191, AMSA and related experimental antitumour acridines in recA+ and recA1 strains of Salmonella typhimurium [13].

Biological context of AMSA

• Structure-activity relationships for thiolytic cleavage rates of antitumor drugs in the 4'-(9-acridinylamino)methanesulfonanilide series [14].
• The intercalator resistance and etoposide sensitivity of the HL-60/AMSA cells themselves were confirmed, and the stability of this pharmacologic phenotype over many hundreds of cell generations was demonstrated [15].
• Topo I/AMSA was found to be about 7-fold less sensitive to CPT than Topo I/p, suggesting the possible involvement of a mutation outside the gene region sequenced (codons 420 to 642) or post-translational modifications of the Topo I enzyme [16].
• Interestingly this line was hypersensitive to camptothecin, a specific inhibitor of topoisomerase I. Restriction endonuclease patterns of the topoisomerase I and topoisomerase II loci were found to be identical in CALc18/AMSA and CALc18 with no evidence of gene amplification and rearrangements [17].
• Effects of AMSA, an antineoplastic agent, on spermatogenesis in the mouse [18].

Anatomical context of AMSA

• Investigation of the use of AMSA either prior to bone marrow transplantation in leukaemia or in association with autologous marrow transplant in neuroblastoma and other solid tumours may be of value [19].
• Relative organ concentrations were similar to those found in mice, except that mice have high AMSA concentration in their spleens whereas our patients did not, even when the spleen was infiltrated with leukemic cells [20].
• The sensitivity of germ cells to AMSA at other stages of differentiation was determined by semiquantitative histologic analysis at 11 days after treatment [18].
• Both the SDS/KCl precipitation assay and the filter-binding assay detected etoposide-induced DNA-protein cross-links in HL-60 and HL-60/AMSA cells and detected a greater frequency of amsacrine-induced DNA-protein cross-links in HL-60 cells than in HL-60/AMSA cells [21].
• One patient with ventricular fibrillation and seizures had high tissue AMSA concentrations in myocardium, but low concentrations in brain [20].

Associations of AMSA with other chemical compounds

• Now we show that purified topoisomerase II from the two cell lines exhibits the same drug sensitivity or resistance as that in the nuclear extracts although the magnitude of the m-AMSA resistance of HL-60/AMSA topoisomerase II in vitro is not as great as the resistance of the intact HL-60/AMSA cells [22].
• The stages of spermatogenic cells killed by the single and fractionated administration of AMSA, an acridine derivative used in cancer chemotherapy, have been identified in the mouse [18].
• Human tissue distribution of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (NSC 141549, AMSA) [20].
• In vitro evaluation of the cardiotoxic potential of AMSA [23].
• Innovations in integrative healthcare education: the AMSA CAM education projects and the University of New Mexico Integrative Medicine Program [24].

Gene context of AMSA

• The two drugs were selected on the basis of their activity in these clones, since AMSA is equally active in cells expressing mutated or wild-type (wt) p53, while DX was much less cytotoxic in cells expressing wt p53 [25].
• In the case of ADR, the ability to circumvent the resistance of HL-60/AMSA suggests additional, non-topoisomerase II-mediated mechanisms of cytolysis that may also explain the broad spectrum of clinical activity of ADR [26].
• Relative organ concentrations of AMSA varied from patient to patient; however, concentrations were generally highest in gallbladder, liver, and kidney, while low levels were generally but not invariably found in lung, testicle, muscle, fat, spleen, bladder, pancreas, colon, prostate, and brain [20].
• Twenty-five consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12 h, days 1-6) and AMSA (120 mg/m2 i.v., days 5-7) [27].
• With this new advanced system in the maxillary arch, the AMSA injection offers clinical advantages over traditional anesthesia techniques, according to Dr. Mark Friedman, whom I consulted with earlier this year [28].

Analytical, diagnostic and therapeutic context of AMSA

• A number of different dose schedules of AMSA were explored, and we conclude that the optimum dose of AMSA for remission induction in acute leukemia is 120 mg/sq m/day for 5 days [3].
• N417/AMSA cells, about 80-fold resistant to mAMSA [4'-(9-acridinylamino)-methanesulfon-m-anisidide], were obtained by serial passages of the parental human small cell lung carcinoma NCI-N417 (N417/p) in stepwise drug concentrations [16].
• The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara-C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients) [29].
• High tissue concentrations of AMSA were still present 2 weeks after treatment [20].
• Concentrations of AMSA were determined by HPLC in autopsy tissue samples from five patients who had received the drug antemortem [20].

References