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Träfflista för sökning "WFRF:(Nagy T.) srt2:(1995-1999)"

Sökning: WFRF:(Nagy T.) > (1995-1999)

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  • Denmeade, Samuel R., et al. (författare)
  • Enzymatic activation of a doxorubicin-peptide prodrug by prostate- specific antigen
  • 1998
  • Ingår i: Cancer Research. - 0008-5472. ; 58:12, s. 2537-2540
  • Tidskriftsartikel (refereegranskat)abstract
    • New approaches to target cytotoxic therapy specifically to metastatic prostate cancer sites are urgently needed. As such an approach, an inactive prodrug was synthesized by coupling the primary amine of doxorubicin to the COOH-terminal carboxyl of a seven-amino acid peptide carrier (i.e., Mu-His- Ser-Ser-Lys-Leu-Gln-Leu). The seven-amino acid peptide was documented to be hydrolyzable specifically by the serine protease prostate-specific antigen (PSA) to liberate the active cytotoxin L-leucyl-doxorubicin. Primary cultures of PC-82 human prostate cancer cells secreted high levels of enzymatically active PSA (i.e., 70 ± 5 ng of enzymatically active PSA/106 cells/24 h), whereas LNCaP human prostate cancer ells produced lower levels of enzymatically active PSA (i.e., 2.3 ± 1 ng/106 cells/24 h). LNCaP cells, however, secreted sufficient amounts of enzymatically active PSA to activate the doxorubicin prodrug to a cytotoxic form in vitro. The specificity of the cytotoxic response to the prodrug was demonstrated by the fact that 70 nM of the prodrug killed 50% of the PSA-producing LNCaP cells, whereas doses as high as 1 ♂ had no cytotoxic effect on PSA-nonproducing TSU human prostate cancer cells in vitro.
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