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Titolo:
Digitonin enhances the antitumor effect of cisplatin during isolated lung perfusion
Autore:
Tanaka, T; Kaneda, Y; Li, TS; Matsuoka, T; Zempo, N; Esato, K;
Indirizzi:
Yamaguchi Univ, Sch Med, Dept Surg 1, Ube, Yamaguchi 7558505, Japan Yamaguchi Univ Ube Yamaguchi Japan 7558505 Ube, Yamaguchi 7558505, Japan
Titolo Testata:
ANNALS OF THORACIC SURGERY
fascicolo: 4, volume: 72, anno: 2001,
pagine: 1173 - 1178
SICI:
0003-4975(200110)72:4<1173:DETAEO>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR; RAT; MODEL; PERMEABILIZATION; METASTASES; MEMBRANE; SARCOMA; INSITU;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Tanaka, T Yamaguchi Univ, Sch Med, Dept Surg 1, 1-1-1 Minami Kogushi, Ube,Yamaguchi7558505, Japan Yamaguchi Univ 1-1-1 Minami Kogushi Ube Yamaguchi Japan 7558505
Citazione:
T. Tanaka et al., "Digitonin enhances the antitumor effect of cisplatin during isolated lung perfusion", ANN THORAC, 72(4), 2001, pp. 1173-1178

Abstract

Background. The antitumor effect of isolated lung perfusion with cisplatinwas limited because the intracellular platinum concentration did not increase sufficiently. To solve this problem, digitonin, a detergent, was chosento increase cell permeability and enhance intracellular uptake and antitumor effect. This study was designed to investigate toxicity, pharmacokinetics, and efficacy of isolated lung perfusion with the combined use of digitonin and cisplatin in Fischer 344 rats. Methods. Systemic and local toxicities of isolated lung perfusion treatment were evaluated on the basis of body weight change, survival rate, and histologic findings. The maximal tolerated dose of digitonin was determined byassessing survival on day 21 after contralateral pneumonectomy, body weight change, and histologic findings. Pharmacokinetics were observed in a solitary lung tumor nodule model by measuring platinum concentration in tumor and normal lung tissue. The antitumor effect was evaluated by the number of tumor nodules in the left lung 21 days after isolated lung perfusion. Isolated lung perfusion was performed 7 days after 1.0 x 10(6) methylcholanthrene sarcoma cells were injected into the external jugular vein. Results. The maximal tolerated dose of digitonin was 20 mu mol/L. Platinumconcentration of tumor nodules in the digitonin-cisplatin-treated rats was20% higher than in the cisplatin-only group (5.48 +/- 0.64 mug/g tissue versus 4.50 +/- 1.09 mug/g tissue; p = 0.067). The number of pulmonary nodules decreased significantly by digitonin use (1.3 +/- 1.5 versus 9.7 +/- 2; p< 0.0001). Conclusions. Isolated lung perfusion with digitonin and cisplatin in combination was performed safely and enhanced the antitumor effect. These drugs in combination show promise for enhancing the effect of clinical isolated lung perfusion. (C) 2001 by The Society of Thoracic Surgeons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:33:24