Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Decrease in drug accumulation and in tumour aggressiveness marker expression in a fenretinide-induced resistant ovarian tumour cell line
Autore:
Appierto, V; Cavadini, E; Pergolizzi, R; Cleris, L; Lotan, R; Canevari, S; Formelli, F;
Indirizzi:
Ist Nazl Tumori, Dept Expt Oncol, I-20133 Milan, Italy Ist Nazl Tumori Milan Italy I-20133 ept Expt Oncol, I-20133 Milan, Italy Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 d & Neck Med Oncol, Houston, TX 77030 USA
Titolo Testata:
BRITISH JOURNAL OF CANCER
fascicolo: 11, volume: 84, anno: 2001,
pagine: 1528 - 1534
SICI:
0007-0920(20010601)84:11<1528:DIDAAI>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARCINOMA-CELLS; BREAST-CANCER; ACID; APOPTOSIS; METABOLISM; RETINAMIDE; INDUCTION; WOMEN; BETA;
Keywords:
retinoids; ovarian tumour; fenretinide-resistance; drug uptake; differentiation; RAR beta;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
19
Recensione:
Indirizzi per estratti:
Indirizzo: Formelli, F Ist Nazl Tumori, Dept Expt Oncol, Via Venezian 1, I-20133 Milan, Italy Ist Nazl Tumori Via Venezian 1 Milan Italy I-20133 lan, Italy
Citazione:
V. Appierto et al., "Decrease in drug accumulation and in tumour aggressiveness marker expression in a fenretinide-induced resistant ovarian tumour cell line", BR J CANC, 84(11), 2001, pp. 1528-1534

Abstract

We investigated whether the efficacy of fenretinide (HPR) against ovarian tumours may be limited by induction of resistance. The human ovarian carcinoma cell line A2780, which is sensitive to a pharmacologically achievable HPR concentration (IC50 = 1 muM), became 10-fold more resistant after exposure to increasing HPR concentrations. The cells (A2780/HPR) did not show cross-resistance to the synthetic retinoid 6-[3 adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and were not sensitive, similarly to theparent line, to all-trans-retinoic acid, 13-cis-retinoic acid or N-(4-methoxyphenyl)retinamide. A2780/HPR cells showed, compared to parental cells, a3-fold reduction in colony-forming ability in agar. The development of HPRresistance was associated with a marked increase in retinoic acid receptorbeta (RAR beta) mRNA and protein levels, which decreased, together with drug resistance, after drug removal. The expression of cell surface moleculesassociated with tumour progression including HER-2, laminin receptor and beta1 integrin was markedly reduced. The increase in the levels of reactive oxygen species is not involved in HPR-resistance because it was similar in parental and resistant cells. Conversely differences in pharmacokinetics may account for resistance because, in A2780/HPR cells, intracellular peak drug levels were 2 times lower than in A2780 cells and an as yet unidentifiedpolar metabolite was present. These data suggest that acquired resistance to HPR is associated with changes in marker expression, suggestive of a more differentiated status and may be explained, at least in part, by reduced drug accumulation and increased metabolism. (C) 2001 Cancer Research Campaign.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 11:08:32