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Titolo:
Pegylated liposomal tumor necrosis factor-alpha results in reduced toxicity and synergistic antitumor activity after systemic administration in combination with liposomal doxorubicin (Doxil (R)) in soft tissue sarcoma-bearing rats
Autore:
Ten Hagen, TLM; Seynhaeve, ALB; Van Tiel, ST; Ruiter, DJ; Eggermont, AMM;
Indirizzi:
Univ Rotterdam Hosp, Dr Daniel Den Hoed Canc Ctr, Dept Surg Oncol, Rotterdam, Netherlands Univ Rotterdam Hosp Rotterdam Netherlands Oncol, Rotterdam, Netherlands Univ Nijmegen Hosp, Dept Pathol, NL-6500 HB Nijmegen, Netherlands Univ Nijmegen Hosp Nijmegen Netherlands NL-6500 HB Nijmegen, Netherlands
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 1, volume: 97, anno: 2002,
pagine: 115 - 120
SICI:
0020-7136(20020101)97:1<115:PLTNFR>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ISOLATED LIMB PERFUSION; TNF-ALPHA; THERAPEUTIC EFFICACY; INTERFERON-GAMMA; MELPHALAN; PHARMACOKINETICS; MICE; DELIVERY; MELANOMA;
Keywords:
pegylated liposomal TNF; liposomal doxorubicin; Doxil (R); soft tissue sarcoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Ten Hagen, TLM Erasmus Univ, Lab Expt Surg Oncol, POB 1738, NL-3000 DR Rotterdam, Netherlands Erasmus Univ POB 1738 Rotterdam Netherlands NL-3000 DRnds
Citazione:
T.L.M. Ten Hagen et al., "Pegylated liposomal tumor necrosis factor-alpha results in reduced toxicity and synergistic antitumor activity after systemic administration in combination with liposomal doxorubicin (Doxil (R)) in soft tissue sarcoma-bearing rats", INT J CANC, 97(1), 2002, pp. 115-120

Abstract

Previously we reported that encapsulation of tumor necrosis factor-alpha (TNF) in pegylated (STEALTH (R)) liposomes (TNF-PEGL) dramatically improved circulation times of the protein and augmented accumulation in tumor tissue. We and others have demonstrated enhanced antitumor activity of doxorubicin or melphalan by free TNF when used in ig doses in an isolated limb perfusion setting. In the present study the antitumor activity of TNF-PEGL was studied in combination with liposomal chemotherapy. BN rats with subcutaneousBN175 sarcomas (8-12 mm diameter) received no treatment or pegylated liposomal doxorubicin (Doxil (R)) alone or in combination with various doses of TNF-PEGL (15-200 mug/kg), The evaluated endpoints were tumor response and toxicity of the treatment regimens. Here we demonstrate that TNF-PEGL at a dose of 15 mug/kg markedly augments the antitumor activity of liposomal doxorubicin, without resulting in the increased toxic side effects observed with free TNF at doses resulting in a similar enhancement of the antitumor effects. Even at a TNF dose of 200 mug/kg TNF, repeated administration of TNF-PEGL did not result in severe weight loss or cause diarrhea. Repeated dosing of free TNF at this dose resulted in severe, life-threatening weight lossand occurrence of diarrhea in all animals. These results indicate that pegylated liposomal encapsulation may be effective in systemic application of TNF for combined treatment with liposomal chemotherapy of advanced solid tumors. (C) 2002 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 21:00:22