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Retinoids are vitamin A (retinol) derivatives essential for normal embryo development and epithelial differentiation. These compounds are also involved in chemoprevention and differentiation therapy of some cancers, with particularly impressive results in the management of acute promyelocytic leukemia (APL). Although highly effective in APL therapy,(More)
Quantitative reverse-transcriptase polymerase chain reaction was used to determine the content of mRNA derived from four CYP3A genes (CYP3A2, CYP3A9, CYP3A18, and CYP3A23) in rat liver. CYP3A2 and CYP3A9 gene expression was age- and sex-dependent, whereas CYP3A18 and CYP3A23 mRNA were observed before and after puberty at fairly constant levels that were(More)
BACKGROUND Irinotecan (CPT-11) is a novel water-soluble camptothecin derivative selected for clinical testing based on its good in vitro and in vivo activity in various experimental systems, including pleiotropic drug-resistant tumors. Its mechanism of action appears mediated through topoisomerase I inhibition. The purpose of this study was to describe(More)
This article reviews the clinical pharmacokinetics of a water-soluble analogue of camptothecin, irinotecan [CPT-11 or 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptoth eci n]. Irinotecan, and its more potent metabolite SN-38 (7- ethyl-10-hydroxy-camptothecin), interfere with mammalian DNA topoisomerase I and cancer cell death appears to result(More)
The purpose of this work was to identify the principal human cytochrome P450s (CYPs) involved in the metabolism of the retinoic acid (RA) isomers, 9-cis- and 13-cis-RA, by using a combination of techniques including human liver microsomes (correlation of activity and inhibition), and lymphoblast microsomes expressing a single CYP. Concerning the 9-cis-RA,(More)
We have shown that four metabolites of all-trans-retinoic acid (ATRA) (4-oxo-, 4-OH-, 18-OH-, and 5,6-epoxy-RA) can induce maturation of NB4 promyelocytic leukemia cells (Idres, N., Benoit, G., Flexor, M. A., Lanotte, M., and Chabot, G. G. (2001) Cancer Res. 61, 700-705). To better understand the mechanism of action of ATRA metabolites and isomers, we(More)
To better understand the importance of drug-metabolizing enzymes in carcinogenesis and anticancer drug sensitivity of human non-small cell lung cancer, we studied the main drug-metabolizing enzyme systems in both lung tumors and their corresponding nontumoral lung tissues in 12 patients. The following enzymes were assayed by Western blot analysis:(More)
BACKGROUND We conducted a phase I and pharmacokinetic study to determine the maximum tolerable dose (MTD), toxicities, pharmacokinetic profile, and antitumor activity of Irinotecan (CPT-11) in patients with refractory solid malignancies. PATIENTS AND METHODS Forty-six patients were entered in this phase I study. CPT-11 was administered intravenously over(More)
PURPOSE To investigate the potential value of magnetic resonance (MR) elastography and diffusion-weighted (DW) MR imaging in the detection of microstructural changes of murine colon tumors during growth and antivascular treatment. MATERIALS AND METHODS The study was approved by the regional ethics committee for animal care. Sixty Balb-C mice, bearing(More)
BACKGROUND Diarrhea is a serious side effect that may prevent the administration of high doses of the antitumor drug Irinotecan (CPT-11). PURPOSE Intensive, high-dose loperamide was used in an attempt to control or downstage CPT-11-induced diarrhea and thus permit the use of higher dose intensities of CPT-11. METHODS Twenty-three patients with various(More)