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- Title
CPT-11 converting carboxylesterase and topoisomerase I activities in tumour and normal colon and liver tissues.
- Authors
Guichard, S; Terret, C; Hennebelle, I; Lochon, I; Chevreau, P; Frétigny, E; Selves, J; Chatelut, E; Bugat, R
- Abstract
CPT-11 is a prodrug activated by carboxylesterases to the active metabolite SN-38 which is a potent inhibitor of topoisomerase I. CPT-11 is of clinical interest in the treatment of colorectal cancer. We evaluated the activities of CPT-11 converting carboxylesterase (CPT-CE) and topoisomerase I (topo I) in 53 colorectal tumours, in eight liver metastases and in normal tissue adjacent to the tumours. Both CPT-CE and topo I activities were widely variable in the malignant and the normal tissue of patients with colorectal carcinomas. CPT-CE was only two to threefold lower in primary tumours compared to normal liver, suggesting that a local conversion to SN-38 might occur in tumour cells. CPT-CE was similar in liver and in normal colon tissues. Levels of topo I in tumour ranged from 580 to 84 900 U mg protein[SUP-1] and was above 40 000 U mg protein[SUP-1] in 11 of 53 patients. Similarly, a very high ratio (> 5) between tumour and normal tissues were observed in 12 of 53 patients. An inverse correlation was observed between the topo I activity and the clinical stage of disease. Clinical studies are in progress in our institution to explore a possible relationship between CPT-CE and topo I activities in tumour cells and the response to CPT-11-based chemotherapy in patients with colorectal cancer.
- Subjects
DNA topoisomerase I; TUMORS; COLON (Anatomy)
- Publication
British Journal of Cancer, 1999, Vol 80, Issue 3/4, p364
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/sj.bjc.6690364