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High Antimetastatic Efficacy of MEN4901/T-0128, a Novel Camptothecin Carboxymethyldextran Conjugate
- Source :
-
Journal of Surgical Research . Dec2011, Vol. 171 Issue 2, p684-690. 7p. - Publication Year :
- 2011
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00224804
- Volume :
- 171
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Surgical Research
- Publication Type :
- Academic Journal
- Accession number :
- 67258491
- Full Text :
- https://doi.org/10.1016/j.jss.2010.05.066