Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to describe the cerebrospinal fluid (CSF) penetration of topotecan in humans, to generate a pharmacokinetic model to simultaneously describe topotecan lactone and total concentrations in the plasma and CSF, and to characterize the CSF and plasma pharmacokinetics of topotecan administered as a continuous infusion (CI). Plasma and CSF samples were collected from 17 patients receiving 5.5 or 7.5 mg/m2 per day as a 24-h CI (5 patients, 7 courses), or 0.5 to 1.25 mg/m2 per day as a 72-h CI (12 patients, 12 courses). CSF samples were obtained from either a ventricular reservoir (VR) or a lumbar puncture (LP). Topotecan lactone and total (lactone plus hydroxy acid) concentrations were determined by HPLC and fluorescence detection. Using MAP-Bayesian modelling, a three-compartment model was fitted simultaneously to topotecan lactone and total concentrations in the plasma and CSF. The penetration of topotecan into the CSF was determined from the ratio of the CSF to the plasma area under the concentration-time curve. The median CSF ventricular lactone concentrations, obtained prior to the end of infusion (EOI), were 0.86, 1.4, 0.73, 5.3, and 4.6 ng/ml for patients receiving 0.5, 1.0, 1.25, 5.5, and 7.5 mg/m2 per day, respectively. EOI CSF lumbar lactone concentrations measured in three patients were 0.44, 1.1, and 1.7 ng/ml for topotecan doses of 1.0, 5.5, and 7.5 mg/m2 per day, respectively. In two patients receiving 1.25 mg/m2 per day, EOI CSF concentrations were obtained simultaneously from a VR and LP; the lumbar lactone concentrations were 30% and 49% lower than the ventricular concentrations. During a 24-h and a 72-h CI, the median CSF penetration of topotecan lactone was 0.29 (range 0.10 to 0.59) and 0.42 (range 0.11 to 0.86), respectively. A three-compartment model adequately described topotecan lactone and total concentrations in the plasma and CSF. Topotecan was therefore found to significantly penetrate into the CSF in humans. The pharmacokinetic model presented may be useful in the design of clinical studies of topotecan to treat CNS tumors.
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PMID:Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. 852 78

The MAP-2 isoform containing exon 13 (MAP-2e) is expressed in human fetal development as early as 15 gestational weeks and parallels oligodendrocyte maturation. MAP-2e is down-regulated following myelination and is expressed in few cells in the adult central nervous system (CNS). To determine whether CNS tumors express MAP-2e, we screened 122 archival, paraffin-embedded adult and pediatric tumors of the CNS and non-CNS. All oligodendrogliomas were positive and extensive staining was observed in glioblastomas, various malignant gliomas and dysembryoplastic neuroepithelial tumors. MAP-2e was not expressed in non-CNS tumors or neuroblastomas. Thus. neuroectodermal tumors that have glial characteristics express this developmental marker of immature glia. Analysis of oligodendrogliomas demonstrated numerous cell morphologies from round cells with no processes to cells with single or multiple processes. MAP-2e immunostaining also delineated tumor invasion into adjacent gray and white matter, indicating that MAP-2e appears to be a useful marker for examining the infiltration of malignant cells into surrounding tissue.
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PMID:MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration. 1202 43