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Titolo:
Tumoricidal activity of a novel anti-human DR5 monoclonal antibody withouthepatocyte cytotoxicity
Autore:
Ichikawa, K; Liu, WM; Zhao, LM; Wang, Z; Liu, D; Ohtsuka, T; Zhang, HG; Mountz, JD; Koopman, WJ; Kimberly, RP; Zhou, T;
Indirizzi:
Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294USA Univ Alabama Birmingham AL USA 35294 & Rheumatol, Birmingham, AL 35294USA Sankyo Co Ltd, Biomed Res Labs, Tokyo 140, Japan Sankyo Co Ltd Tokyo Japan 140 Co Ltd, Biomed Res Labs, Tokyo 140, Japan
Titolo Testata:
NATURE MEDICINE
fascicolo: 8, volume: 7, anno: 2001,
pagine: 954 - 960
SICI:
1078-8956(200108)7:8<954:TAOANA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; APOPTOSIS-INDUCING LIGAND; TRAIL-INDUCED APOPTOSIS; FADD-DEPENDENT APOPTOSIS; DEATH DOMAIN; RECEPTOR; CASPASE-8; FAMILY; MEMBER; ACTIVATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Zhou, T Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294USA Univ Alabama Birmingham AL USA 35294 tol, Birmingham, AL 35294USA
Citazione:
K. Ichikawa et al., "Tumoricidal activity of a novel anti-human DR5 monoclonal antibody withouthepatocyte cytotoxicity", NAT MED, 7(8), 2001, pp. 954-960

Abstract

A novel anti-human DR5 monoclonal antibody, TRA-8, induces apoptosis of most tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-sensitive tumor cells both in vitro and in vivo. In contrast to both the membrane-bound form of human TRAIL, which induced severe hepatitis in mice, and the soluble form of human TRAIL, which induced apoptosis of normal human hepatocytes in vitro, TRA-8 did not induce significant cell death of normal human hepatocytes. However, both primary hepatocellular carcinoma cells and an established liver cancer cell line were highly susceptible to the killing mediated by TRA-8. We show here that elevated levels of cell-surface expression of DRS and increased susceptibility to DRS-mediated apoptosis are characteristics of malignant tumor cells. In contrast, DR5 alone is not sufficientto trigger apoptosis of normal hepatocytes. Therefore, selective, specifictargeting of DR5 with an agonistic antibody might be a safe and effective strategy for cancer therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:47:42