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Activity of oral and intravenous 9-aminocamptothecin in SCID mice engrafted with human leukemia.

Abstract
The intravenous (i.v.) injection of the human acute myelogenous leukemia cell line KBM-3 into severe combined immune deficient (SCID) mice results in disseminated multi-organ human disease involvement in these animals which leads to their death over a defined period of time. We utilized this model of human leukemia to investigate the in vivo therapeutic efficacy of the topoisomerase I inhibitor 9-aminocamptothecin (9-AC) given by two different routes. Mice injected with KBM-3 were divided into five groups. Group 1 received only diluent and served as control. The four remaining groups were treated with 9-AC four days a week for three consecutive weeks as follows: group 2 received 1.33 mg/kg/dose, i.v.; group 3, 1.33 mg/kg/dose, orally (p.o.); group 4, 2.0 mg/kg/dose i.v. and group 5, 2.0 mg/kg/dose p.o.. All animals in the control group died from disseminated human leukemia by day 64 from grafting, with a median survival of 59 days. Eleven out of 20 treated mice survived with no evidence of disease and were sacrificed at the termination of the experiment on day 128. PCR-assisted tissue analysis for the presence of human DNA showed no evidence of human leukemia. In conclusion, 9-AC is an active agent in SCID mice engrafted with human myelogenous leukemia and should be explored in phase I-II trials. Oral and intravenous routes are equally effective.
AuthorsS Jeha, H Kantarjian, S O'Brien, L Vitek, M Beran
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 32 Issue 1-2 Pg. 159-64 (Dec 1998) ISSN: 1042-8194 [Print] United States
PMID10037011 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQA1 antigen
  • 9-aminocamptothecin
  • Camptothecin
Topics
  • Acute Disease
  • Administration, Oral
  • Animals
  • Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • HLA-DQ Antigens (metabolism)
  • HLA-DQ alpha-Chains
  • Humans
  • Injections, Intravenous
  • Leukemia, Experimental (drug therapy, metabolism, mortality)
  • Leukemia, Myeloid (drug therapy, metabolism, mortality)
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Survival Rate

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