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.
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Authors | S Jeha, H Kantarjian, S O'Brien, L Vitek, M Beran |
Journal | Leukemia & lymphoma
(Leuk Lymphoma)
Vol. 32
Issue 1-2
Pg. 159-64
(Dec 1998)
ISSN: 1042-8194 [Print] United States |
PMID | 10037011
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- HLA-DQ Antigens
- HLA-DQ alpha-Chains
- HLA-DQA1 antigen
- 9-aminocamptothecin
- Camptothecin
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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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