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Titolo:
Prevention of human prostate tumor metastasis in athymic mice by antisensetargeting of human angiogenin
Autore:
Olson, KA; Byers, HR; Key, ME; Fett, JW;
Indirizzi:
Harvard Univ, Sch Med, Ctr Biochem & Biophys Sci & Med, Cambridge, MA 02139 USA Harvard Univ Cambridge MA USA 02139 ys Sci & Med, Cambridge, MA 02139 USA Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02139 USA Harvard Univ Cambridge MA USA 02139 Dept Pathol, Cambridge, MA 02139 USA Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA Boston Univ Boston MA USA 02118 Med, Dept Dermatol, Boston, MA 02118 USA Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA Boston Univ Boston MA USA 02118 ch Med, Dept Pathol, Boston, MA 02118 USA Dako Corp, Carpinteria, CA 93013 USA Dako Corp Carpinteria CA USA 93013Dako Corp, Carpinteria, CA 93013 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 11, volume: 7, anno: 2001,
pagine: 3598 - 3605
SICI:
1078-0432(200111)7:11<3598:POHPTM>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; NUDE-MICE; CARCINOMA-CELLS; IN-VITRO; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; MESSENGER-RNA; HUMAN CANCER; PROTEIN; MOUSE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Fett, JW Harvard Univ, Sch Med, Ctr Biochem & Biophys Sci & Med, 1 KendallSq,Bldg 600 3rd Floor, Cambridge, MA 02139 USA Harvard Univ 1 Kendall Sq,Bldg 600 3rd Floor Cambridge MA USA 02139
Citazione:
K.A. Olson et al., "Prevention of human prostate tumor metastasis in athymic mice by antisensetargeting of human angiogenin", CLIN CANC R, 7(11), 2001, pp. 3598-3605

Abstract

Purpose: Angiogenin is a potent positive mediator of neovascularization, aprocess required for both primary tumor growth and metastasis. In the present study, the effect of a fully phosphorothioated antisense oligodeoxynucleotide, designated JF2S, targeting the AUG translation initiation codon region of human angiogenin, on human prostate tumor development and metastasisin athymic mice was examined. Experimental Design: JF2S, was evaluated for its capacity to affect in vitro synthesis or angiogenin and subsequent tumorigenicity of transiently transfected prostate tumor cells in mice. In vivo treatment experiments were then conducted in which JF2S was used to prevent formation of tumors in an ectopic model and metastasis in an orthotopic model. Results: Transient transfection of tumor cells with JF2S inhibited both angiogenin gene expression in vitro and tumorigenicity of these transfected cells in athymic mice. In therapy experiments, local treatment with JF2S completely protected mice from developing prostate tumors after s.c. injectionof PC-3 human prostate tumor cells (P < 0.0001, survivor analysis). Most importantly, systemic prophylactic administration of JF2S prevented, in 47% of mice, formation of regional iliac lymph node micrometastases arising from primary tumors growing in the more natural orthotopic prostate setting (P= 0.0003, Fisher's exact test). Furthermore, total protection from regional metastasis occurred in those mice in which JF2S treatment successfully diminished human angiogenin expression in vivo. Tumor-associated angiogenesiswas also impaired by JF2S treatment. When therapy was delayed until all ofthe mice harbored primary tumors in the prostate, the incidence of regional metastasis was still significantly decreased (P < 0.005, survivor analysis). Conclusions: These findings demonstrate that human prostate cancer establishment and spread in athymic. mice is extremely susceptible to targeted disruption of tumor-derived human angiogenin gene expression. Therefore, angiogenin is a valid target against which to devise preventative strategies forprostate cancer metastasis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 06:47:32