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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Clinically, amsacrine has an activity and toxicity profile similar to doxorubicin and has been used to treat acute lymphoblastic and myeloid leukemias, and advanced ovarian carcinomas. In the UK, it is recommended by NICE for the treatment of acute leukemia refractory to anthracycline chemotherapy either alone or in combination with other chemotherapy agents.
Differentiation Induction in Acute Promyelocytic Leukemia
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
It is not clear if one anthracycline or the other is more effective for induction in APL. Fenaux et al. prospectively randomized patients to either rubidizone or amsacrine, each with ara-C, without observing a difference between the anthracyclines (19). There was a suggestion in a retrospective analysis that idarubicin was associated with an improved outcome, but no prospective randomized trial compared idarubicin with other anthracyclines (20). Although anthracyclines improve OS, early death from bleeding and high relapse rates characterize the predifferentiation era of APL treatment.
Intensified conditioning regimen with fludarabine combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in children with high-risk acute leukemia
Published in Hematology, 2023
Junjie Cao, Xiaodong Xu, Ying Lu, Tiantian Wang, Dong Chen, Shuangyue Li, Xuhui Liu, Peipei Ye, Zhong-zheng Zheng, Renzhi Pei
The combination of Flu with high-dose Ara-C increases the intracellular Ara-C content in leukemic cells, which has shown a synergistic effect. Thus, administration of Flu prior to Ara-C may enhance the clinical efficacy of Ara-C. Several studies have added mitoxantrone, amsacrine, or idamycin in combination with FLAG scheme, to achieve better prognosis for refractory and recurrent AML patients [22–24]. Flu and Ara-C have synergistic effect. The application of Flu in the first 4 h of Ara-C could increase the concentration of Ara-c in tumor cells, and the chance of cross-resistance is low; The FLAG intervention composed of Flu, Ara-C, and G-CSF has been widely used in the treatment of refractory and recurrent leukemia or pretreatment of allo-HSCT, and achieved good results [25,26]. Some studies tried to incorporate drugs such as mitoxantrone or idarubicin to the FLAG pretreatment to intensify the pretreatment. However, drug-related heart damage limited the application of this protocol. Considering the safety and efficacy of pretreatment, we increased the dose of Ara-C in FLAG conditioning regimen, in order to enhance the intensity of the pretreatment regimen and reduce the later recurrence.
In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Jana Janockova, Jan Korabecny, Jana Plsikova, Katerina Babkova, Eva Konkolova, Dana Kucerova, Jana Vargova, Jan Koval, Rastislav Jendzelovsky, Peter Fedorocko, Jana Kasparkova, Viktor Brabec, Jan Rosocha, Ondrej Soukup, Slavka Hamulakova, Kamil Kuca, Maria Kozurkova
In this work, new 12 analogs were synthesized by amalgamating THA with the less toxic THA derivative 7-MEOTA via an alkyl chain containing either urea or thiourea moieties. These two parent compounds were formerly anti-Alzheimer’s disease (AD) agents structurally resembling amsacrine or the imidazoacridinones, both being developed as anticancer agents capable to intercalate between DNA-bases and to target Topo II37,38. Our study disclosed their antiproliferative effect against human acute promyelocytic leukemia cell line HL-60 in contrast to their effect on dermal fibroblasts. In summary, herein we provide deep insight into the mode of action of compounds 12–22 that might lead to development of novel DNA topoisomerase inhibitors as chemotherapeutic agents.
Drug treatment options for acute promyelocytic leukemia
Published in Expert Opinion on Pharmacotherapy, 2022
Felicetto Ferrara, Matteo Molica, Massimo Bernardi
Between 1980 and 1988, several reports focused on the efficacy of anthracycline-based regimens [31–33]. Chemotherapy approaches including the combination of an anthracycline and Ara-C became the frontline treatment for APL (Table 1). CR rates reached 80% in newly diagnosed patients, with amsacrine or daunorubicin and Ara-C combination [34]. However, the 5-year disease-free survival (DFS) was only 35–45% and the 2-year relapse rate was about 35%. More intensive anthracycline treatments were used to potentially reduce therapy-resistance and, to further improve long-term survival, maintenance of CR with 6-mercaptopurine and methotrexate was adopted [32–38].