High antimetastatic efficacy of MEN4901/T-0128, a novel camptothecin carboxymethyldextran conjugate.
J Surg Res
; 171(2): 684-90, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-20851421
ABSTRACT
The antimetastatic activity of a novel camptothecan conjugate, MEN4901/T-0128, in which 7-ethyl-10-aminopropyloxy-camptothecin (T-2513) is bound to a biodegradable carboxymethyldextran via a Gly-Gly-Gly linker, was observed in this study. High antimetastatic activity of MEN4901/T-0128 was demonstrated in a clinically-relevant orthotopic mouse model of human colon cancer. MEN4901/T-0128 and irinotecan were compared for anti-metastatic activity as well as efficacy against the primary tumor. An imageable, metastatic model was made by surgical orthotopic implantation (SOI) of the green fluorescent protein (GFP)-expressing HT-29 tumor in nude mice. MEN4901/T-0128 and irinotecan were administered intravenously at various doses and schedules. MEN4901/T-0128, with treatment beginning on d 49 after SOI, was highly effective on lymph node metastasis as well as against the primary tumor. Both GFP imaging and histology demonstrated a markedly lower metastatic incidence of lymph nodes in all MEN4901/T-0128 treated mice compared with irinotecan-treated and untreated mice. At the most efficacious dose of MEN4901/T-0128, only 1 of 12 animals had lymph node metastasis compared with 19 of 20 in the control group. The present study demonstrates the principle that when a camptothecan is conjugated to an appropriate polymer, the drug can become extremely effective with important clinical potential for antimetastatic therapy, a most urgent need.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Camptotecina
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Pró-Fármacos
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Adenocarcinoma
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Dextranos
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Neoplasias do Colo
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Topotecan
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article