Metabolism of 5-fluorouracil in human liver: An in vivo <SUP>19</SUP> F NMR study

In vivo fluorine 19 nuclear magnetic resonance 19F NMR) spectroscopy was used to study the metabolism and pharmacokinetics of 5-fluorouracil (5-FU) in human liver. Nine patients received 5-FU, and additional chemotherapeutic agents (methotrexate, leucovorin, or levarnisole) either prophylac­ tically after breast cancer surgery or for colorectal cancer. The time constant for the disappearance of 5-FU from the liver in vivo varied from S to 17 min, while the time constant for the appearance of &#945;-fluoro-&#946;-alanine (the major catabolite of 5-FU) varied from 7 to 86 min. The modulators of 5-FU metabolism did not appear to affect the time constant for the disappearance of 5-FU from the liver or for the appearance of &#945;-fluoro-&#946;-alanine. Results obtained indicate that the pharmacokineties of S-FU and &#945;-fluoro-&#946;-alanine may vary substantially at different times in a given individual

Fulfilling young potential The success of the Wider Horizons Programme

SIGLEAvailable from British Library Document Supply Centre-DSC:m00/14354 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Bioinformatic analysis of identified biomarkers.

<p><b>A.</b> Gene ontology analysis shows proteins involved in fatty acid binding. platelet degranulation. serine protease inhibitor activity and hydrogen peroxide catabolic processes. <b>B</b> Interaction network of identified biomarker candidates involving 18 out of the 19 proteins. Proteins involved in inflammation. acute phase response (including cellular adhesion). signaling via lipid-mediated pathways (including transport) and activation of proteolytic cascades. as well as transcriptional activity are indicated. Red diamonds indicate proteins which are significant after correction for multiple testing. and grey ones are the remainder of the query set. Circles indicate gap-fillers which were added to connect proteins via protein-protein interactions. Direct association between the significant biomarker set are indicated by a bold line. and relate to immune response (immunoglobulin cluster). protease inhibitor activity. and an activation of the peroxisome proliferator-activated receptor signaling pathway/CDC42 signal transduction pathway. as suggested through APOA1 interactions. <b>C.</b> Kyoto encyclopedia of genes and genomes pathway analysis. Statistically relevant biomarker proteins were mapped onto KEGG pathway maps and showed an involvement of fibril formation and inhibition of fibrinolysis in the coagulation cascade and association with arachidonic acid metabolism.</p

Proteins in vitreous humor detected by CE-MS and identified by LC-MS/MS analysis.

<p>*Uniprot accession numbers that can be found on <a href="http://www.uniprot.org" target="_blank">www.uniprot.org</a>; ** Number of peptides observed by CE-MS analysis and sequenced by LC-MS/MS for each identified protein; *** Percentage of peptide coverage of the protein sequence; ****, Number of peptides observed by CE-MS and sequenced by LC-MS/MS in controls or cases.</p

Study design and results.

<p>Study design and results.</p