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Titolo:
The role of apoptosis in 2 ',2 '-difluoro-2 '-deoxycytidirne (gemcitabine)-mediated radiosensitization
Autore:
Lawrence, TS; Davis, MA; Hough, A; Rehemtulla, A;
Indirizzi:
Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 adiat Oncol, Ann Arbor, MI 48109 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 2, volume: 7, anno: 2001,
pagine: 314 - 319
SICI:
1078-0432(200102)7:2<314:TROAI2>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
RADIATION-INDUCED APOPTOSIS; WEIGHT DNA FRAGMENTATION; COLON-CARCINOMA CELLS; IONIZING-RADIATION; GEMCITABINE; CANCER; P53; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Lawrence, TS Univ Michigan, Dept Radiat Oncol, 1331 E Ann St, Ann Arbor, MI 48109 USA Univ Michigan 1331 E Ann St Ann Arbor MI USA 48109 48109 USA
Citazione:
T.S. Lawrence et al., "The role of apoptosis in 2 ',2 '-difluoro-2 '-deoxycytidirne (gemcitabine)-mediated radiosensitization", CLIN CANC R, 7(2), 2001, pp. 314-319

Abstract

The nucleoside analogue Gemcitabine [2',2'-difluoro-2'-deoxycytidine (dFdCyd)] is active against a wide variety of solid tumors and is a potent radiation sensitizer. Because apoptosis has been shown to be an important mechanism of cell death for many cancers, we wished to investigate the role of apoptosis in dFdCyd-mediated radiosensitization. We evaluated HT29 colon cancer cells, UMSCC-6 head and neck cancer cells, and A549 lung cancer cells, which differ substantially in the ability to undergo radiation-induced apoptosis, We hypothesized that if dFdCyd produced radiosensitization by potentiating preexisting death pathways, then only the apoptotic-prone HT29 cells would show a substantial increase in apoptosis when treated with the combination of dFdCyd and radiation and that UMSCC-6 cells and A549 cells would be radiosensitized through nonapoptotic mechanisms. We found that the radiosensitization of HT29 cells (enhancement ratio, 1.81 +/- 0.16) was accompanied by an increase in apoptosis and by caspase activation and that inhibition of this activation by the caspase inhibitor Z-Asp-Glu-Val-Asp-fluoromethylketone (DEVD) significantly decreased radiosensitization (to 1.36 +/- 0.24; P < 0.05). In contrast, UMSCC-6 cells and A549 cells were modestly radiosensitized (enhancement ratio, 1.47 +/- 0.24 and 1.31 +/- 0.04, respectively) via a nonapoptotic mechanism. These findings suggest that although apoptosis can contribute significantly to dFdCyd-mediated radiosensitization, therole of apoptosis in dFdCyd-mediated radiosensitization depends on the cell line rather than representing a general property of the drug.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 12:46:01