Human CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exert a potent anti-lymphoma effects by targeting tumor vasculature. (Abstract/Comunicazione in atti di convegno)

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  • Human CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exert a potent anti-lymphoma effects by targeting tumor vasculature. (Abstract/Comunicazione in atti di convegno) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • Carlo-Stella, C (Carlo-Stella, Carmelo)1,4; Lavazza, C (Lavazza, Cristiana)1,4; Giacomini, A (Giacomini, Arianna)1,4; Sia, D (Sia, Damela)1,4; Cleris, L (Cleris, Loredana)1; Di Niola, M (Di Niola, Massimo)1; Longoni, P (Longoni, Paolo)1; Milanesi, M (Milanesi, Marco)1; Magni, M (Magni, Michele)1; Righi, M (Righi, Marco)2; Francolini, M (Francolini, Maura)2; Gloghini, A (Gloghini, Annunziata)3; Guidetti, A (Guidetti, Anna)1; Carbone, A (Carbone, Antonino)1; Gianni, AM (Gianni, Alessandro M.)1,4 (2007)
    Human CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exert a potent anti-lymphoma effects by targeting tumor vasculature.
    in ASH Annual Meeting, Atlanta, Georgia, 8-11, December, 2007
    (literal)
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  • Carlo-Stella, C (Carlo-Stella, Carmelo)1,4; Lavazza, C (Lavazza, Cristiana)1,4; Giacomini, A (Giacomini, Arianna)1,4; Sia, D (Sia, Damela)1,4; Cleris, L (Cleris, Loredana)1; Di Niola, M (Di Niola, Massimo)1; Longoni, P (Longoni, Paolo)1; Milanesi, M (Milanesi, Marco)1; Magni, M (Magni, Michele)1; Righi, M (Righi, Marco)2; Francolini, M (Francolini, Maura)2; Gloghini, A (Gloghini, Annunziata)3; Guidetti, A (Guidetti, Anna)1; Carbone, A (Carbone, Antonino)1; Gianni, AM (Gianni, Alessandro M.)1,4 (literal)
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  • 162A (literal)
Pagina fine
  • 162A (literal)
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  • Prodotto visualizzabile alla URL http://abstracts.hematologylibrary.org.pros.lib.unimi.it/cgi/content/abstract/110/11/527?maxtoshow=&hits=10&RESULTFORMAT=1&author1=Carlo-Stella%2C+C&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=110&resourcetype=HWCIT (literal)
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  • 110 (literal)
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  • 11 (literal)
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  • ISI Web of Science (WOS) (literal)
  • Abstract (literal)
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  • 1. Ist Nazl Tumori, Milan, Italy 2. Univ Milan, Dept Pharmacol, I-20122 Milan, Italy 3. Ctr Riferimento Oncol, Diagnost Immunohistochem & Mol Pathol Unit, Aviano, Italy 4. Univ Milan, I-20122 Milan, Italy (literal)
Titolo
  • Human CD34+ cells expressing membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exert a potent anti-lymphoma effects by targeting tumor vasculature. (literal)
Abstract
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expected to play a key role in cancer therapy due to its high cancer cell-specificity and potent antitumor activity. We have previously demonstrated that CD34+ cells transduced with an adenovirus encoding the full-length human TRAIL gene (CD34-TRAIL+) exert a potent anti-lymphoma effect in NOD/SCID mice. To investigate the mechanism of action of CD34-TRAIL+ cells, in vivo experiments were perfomed to analyze 1. the tumor homing capacity of CD34-TRAIL+ cells and 2. the effects of transduced cells on tumor vasculature. Tumor homing of CD34-TRAIL+ cells was investigated in NOD/SCID mice bearing subcutaneous lymphoid tumors. Following a single intravenous injection of CD34-TRAIL+ cells (5 x 106), nodules were excised at different time-points and immunostained with an anti-human CD45 antibody. Sections were digitally recorded and the total number of CD45+ cells per tissue section was then counted using the imaging software ImageJ (http://rsb.info.nih.gov/ij/). Tumor homing of CD34-TRAIL+ cells peaked 24 hours after cell injection when a mean of 200 CD34-TRAIL+ cells was recorded per 1 x 105 tumor cells (0.2% CD45+ cells per 1 x 105 tumor cells). Mice pretreatment with the anti-VCAM-1 antibody or the CXCR4 antagonist AMD3100 significantly reduced tumor homing of CD34-TRAIL+ cells, with 0.09% and 0.05% CD45+ cells being recorded per 1 x 105 tumor cells, respectively. To analyze the effects of CD34-TRAIL+ cells on tumor vasculature, mice were injected with sulfo-biotin (0.1 mg, IV, 15 min) and tumor endotelial cells (TEC) were then revealed by staining frozen sections with horseradish peroxidase (HRP)-conjugated streptavidin. As compared with CD34-mock- or soluble (s)TRAIL-treated mice, treatment with CD34-TRAIL+ cells induced within 24 hours a significant (P <=.001) increase of the thickness of the vessell wall (3.7 ± 1 µm vs 3.4 ± 1 µm vs 6 ± 1 µm, respectively) as well as the endothelial surface (10 ± 4% vs 7 ± 4% vs 21 ± 6% of total tissue section, respectively), suggesting that CD34-TRAIL+ cells induce an early vascular disruption. Confocal microscopic imaging of tumor sections double-stained with anti-CD31 and anti-TRAIL-R2 showed that this receptor was expressed by 8-12% of large tumor vessels. Interestingly, upon treatment with CD34-TRAIL+ cells, but not sTRAIL, TUNEL staining revealed an extensive apoptosis of CD31+/TRAIL-R2+ TEC. Forty-eight hours following injection of CD34-TRAIL+ cells, a 21-fold increase of apoptotic index was detected, which was associated with extensive necrotic areas (20% to 25% of tissue section). These data show that: 1. tumor homing of CD34-TRAIL+ cells induces extensive vascular damage, hemorrhagic necrosis and tumor destruction; 2. the antitumor effect of CD34-TRAIL+ cells is mediated by both indirect vascular-disrupting mechanisms and direct tumor cell killing. Footnotes Disclosure: No relevant conflicts of interest to declare. (literal)
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