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Titolo:
Preclinical evaluation of the orally active camptothecin analog, RFS-2000 (9-nitro-20(S)-camptothecin) as a radiation enhancer
Autore:
Amorino, GP; Hercules, SK; Mohr, PJ; Pyo, H; Choy, H;
Indirizzi:
Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 iat Oncol, Nashville, TN 37232 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
fascicolo: 2, volume: 47, anno: 2000,
pagine: 503 - 509
SICI:
0360-3016(20000501)47:2<503:PEOTOA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOPOISOMERASE-I INHIBITORS; MALIGNANT MELANOMA-CELLS; DNA-REPAIR; IONIZING-RADIATION; MAMMALIAN-CELLS; POTENTIALLY LETHAL; SUBLETHAL DAMAGE; 9-NITROCAMPTOTHECIN; TOPOTECAN; 9-AMINOCAMPTOTHECIN;
Keywords:
radiation; RFS-2000; camptothecin; lung cancer; radiotherapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Choy, H Vanderbilt Clin B902, Dept Radiat Oncol, 1301 22nd Ave S, Nashville, TN 37232 USA Vanderbilt Clin B902 1301 22nd Ave S Nashville TN USA 3723232 USA
Citazione:
G.P. Amorino et al., "Preclinical evaluation of the orally active camptothecin analog, RFS-2000 (9-nitro-20(S)-camptothecin) as a radiation enhancer", INT J RAD O, 47(2), 2000, pp. 503-509

Abstract

Purpose: To test for enhancement of radiation effects in vitro and in vivoby the orally administered camptothecin derivative, 9-nitrocamptothecin (RFS-2000); to study whether the mechanism of this enhancement involves inhibition of sublethal damage recovery. Methods and Materials: In vitro: H460 human lung carcinoma cells were incubated with RFS-2000 for various times at 37 degrees C, irradiated, immediately rinsed, and assessed for colony-forming ability. Sublethal damage recovery (SLDR) was also assessed using two split doses of radiation. In vivo: H460 cell xenografts were used in nude mice. Tumors were grown subcutaneously on the flank, then treated with RFS-2000 (1 mg/kg) and/or radiation (2 Gy) for 5 consecutive days. Tumor growth delay was then measured for each treatment group. Results: Radiation enhancement was observed in vitro for incubation times between 4 and 24 hr with 10 nM RFS-2000. Using a 24-hr treatment, the radiation dose enhancement ratio values (DER) for 5, 10, and 15 nM were 1.22, 1.54, and 2.0, respectively. Incubation with 10 nM RFS-2000 inhibited SLDR bya factor of 2. The results of three independent in vivo experiments showedthat RFS-2000 can enhance the effects of fractionated radiotherapy, with an enhancement factor (EF) of 1.64. Conclusion: Our results show that RFS-2000 can enhance the effects of radiation in human lung cancer cells both in vitro and in vivo, and that the mechanism of this effect may involve the inhibition of SLDR. (C) 2000 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 00:42:05