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Titolo:
TAMOXIFEN SYNERGIZES THE ANTIPROLIFERATIVE EFFECT OF CISPLATIN IN HUMAN OVARIAN-CANCER CELLS - ENHANCEMENT OF DNA PLATINATION AS A POSSIBLEMECHANISM
Autore:
ERCOLI A; SCAMBIA G; DEVINCENZO R; ALIMONTI A; PETRUCCI F; FATTOROSSI A; ISOLA G; PANICI PB; CAROLI S; MANCUSO S;
Indirizzi:
CATHOLIC UNIV SACRED HEART,DEPT GYNECOL,LAB ANTINEOPLAST PHARMACOL,LARGO A GEMELLI 8 I-00168 ROME ITALY CATHOLIC UNIV SACRED HEART,DEPT GYNECOL,LAB ANTINEOPLAST PHARMACOL I-00168 ROME ITALY IST SUPER SANITA,DEPT ANALYT CHEM,APPL TOXICOL LAB I-00161 ROME ITALY
Titolo Testata:
Cancer letters
fascicolo: 1, volume: 108, anno: 1996,
pagine: 7 - 14
SICI:
0304-3835(1996)108:1<7:TSTAEO>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESTROGEN-BINDING-SITES; CLONOGENIC-ASSAY; RESISTANCE; MELANOMA; LINE; CIS-DIAMMINEDICHLOROPLATINUM(II); CARCINOMA; PLATINUM; TRIAL;
Keywords:
TAMOXIFEN; CISPLATIN; SYNERGISTIC ACTIVITY; DNA PLATINATION; CISPLATIN-RESISTANCE; OVARIAN CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
A. Ercoli et al., "TAMOXIFEN SYNERGIZES THE ANTIPROLIFERATIVE EFFECT OF CISPLATIN IN HUMAN OVARIAN-CANCER CELLS - ENHANCEMENT OF DNA PLATINATION AS A POSSIBLEMECHANISM", Cancer letters, 108(1), 1996, pp. 7-14

Abstract

We investigated the chemosensitizing activity of tamoxifen (TAM) on estrogen receptor negative ovarian cancer cell lines sensitive (A2780 WT) and resistant to cisplatin (CP) (A2780 CP3). Our results showed that the treatment of both cell lines with the association TAM + CP (concentration range 0.01-1 mu N and 0.1-1 mu g/ml, respectively) results in a synergistic antiproliferative activity and a complete reversal of the acquired CP-resistant phenotype. We demonstrated that in A2780 cells the addition of TAM to CP treatment is able to significantly enhance at every tested CP dose (P < 0.001) the amount of platinum (Pt) bound to the DNA. Since Pt-DNA levels in the genome are clearly related tothe growth inhibitory effect of CP (correlation value = 0.97, P < 0.001) in our experimental model, we hypothesized that TAM could act synergistically with CP and overcome the acquired CP-resistance by enhancing Pt binding to the DNA. We suggest that, from a clinical point of view, TAM may be usefully included in CP-based chemotherapy regimens forovarian cancer patients since plasma concentrations of the drug capable of in vitro CP resistance modulation are achievable in vivo. A prospective clinical trial to verify the clinical usefulness of combined TAM + CP treatment in ovarian cancer patients refractory to prior Pt-based chemotherapy is now underway in our department.

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Documento generato il 21/09/20 alle ore 03:29:19