Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature. (Articolo in rivista)

Type
Label
  • Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature. (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1182/blood-2009-08-239632 (literal)
Alternative label
  • Lavazza C, Carlo-Stella C, Giacomini A, Cleris L, Righi M, Sia D, Di Nicola M, Magni M, Longoni P, Milanesi M, Francolini M, Gloghini A, Carbone A, Formelli F and Gianni AM (2010)
    Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature.
    in Blood
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Lavazza C, Carlo-Stella C, Giacomini A, Cleris L, Righi M, Sia D, Di Nicola M, Magni M, Longoni P, Milanesi M, Francolini M, Gloghini A, Carbone A, Formelli F and Gianni AM (literal)
Pagina inizio
  • 2231 (literal)
Pagina fine
  • 2240 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 115 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 11 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Lavazza, C (Lavazza, Cristiana)2; Carlo-Stella, C (Carlo-Stella, Carmelo)1,2; Giacomini, A (Giacomini, Arianna)2; Cleris, L (Cleris, Loredana); Righi, M (Righi, Marco)3; Sia, D (Sia, Daniela)2; Di Nicola, M (Di Nicola, Massimo); Magni, M (Magni, Michele); Longoni, P (Longoni, Paolo); Milanesi, M (Milanesi, Marco); Francolini, M (Francolini, Maura)2; Gloghini, A (Gloghini, Annunziata); Carbone, A (Carbone, Antonino); Formelli, F (Formelli, Franca); Gianni, AM (Gianni, Alessandro M.)2 (literal)
Titolo
  • Human CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand target both tumor cells and tumor vasculature. (literal)
Abstract
  • Adenovirus-transduced CD34(+) cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL(+) cells) exert potent antitumor activity. To further investigate the mechanism(s) of action of CD34-TRAIL(+) cells, we analyzed their homing properties as well as antitumor and antivascular effects using a subcutaneous myeloma model in immunodeficient mice. After intravenous injection, transduced cells homed in the tumor peaking at 48 hours when 188 plus or minus 25 CD45(+) cells per 10(5) tumor cells were detected. Inhibition experiments showed that tumor homing of CD34-TRAIL(+) cells was largely mediated by vascular cell adhesion molecule-1 and stromal cell-derived factor-1. Both CD34-TRAIL(+) cells and soluble (s) TRAIL significantly reduced tumor volume by 40% and 29%, respectively. Computer-aided analysis of TdT-mediated dUTP nick end-labeling-stained tumor sections demonstrated significantly greater effectiveness for CD34-TRAIL(+) cells in increasing tumor cell apoptosis and necrosis over sTRAIL. Proteome array analysis indicated that CD34-TRAIL(+) cells and sTRAIL activate similar apoptotic machinery. In vivo staining of tumor vasculature with sulfosuccinimidyl-6-(biotinamido) hexanoate-biotin revealed that CD34-TRAIL(+) cells but not sTRAIL significantly damaged tumor vasculature, as shown by TdT-mediated dUTP nick end-labeling(+) endothelial cells, appearance of hemorrhagic areas, and marked reduction of endothelial area. These results demonstrate that tumor homing of CD34-TRAIL(+) cells induces early vascular disruption, resulting in hemorrhagic necrosis and tumor destruction. (literal)
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