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Differential in vitro sensitivity to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas cell lines is linked to tubulin-beta-III expression.

BELLONE, Stefania;SARTORI, Enrico;PECORELLI, Sergio;
2011-01-01
2011
Nessuno
LS4_8 Non-communicable diseases (except for neural/psychiatric, immunity-related, metabolism-related disorders, cancer and cardiovascular diseases)
LS7_9 Health services, health care research
LS7_3 Pharmacology, pharmacogenomics, drug discovery and design, drug therapy
GYNECOLOGIC ONCOLOGY
WOS:000301879600041
Sì, ma tipo non specificato
Inglese
Internazionale
unico
_
_
Abstract OBJECTIVE: To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas (CS). METHODS: Five primary carcinosarcoma cell lines, two from uterine and three of ovarian origin, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. To identify potential mechanisms underlying the differential sensitivity/resistance to patupilone, expression levels of β-tubulin III (TUBB3) were determined with quantitative-real-time-polymerase-chain-reaction (q-RT-PCR) in primary uterine and ovarian CS cell lines and in 26 uterine and 9 ovarian CS fresh-frozen-tissues. RESULTS: No appreciable difference in sensitivity to patupilone versus paclitaxel was noted in ovarian CS cell lines, or when uterine and ovarian CS cell lines were compared in their response to paclitaxel. In contrast, uterine CS cell lines were found to be significantly more sensitive to patupilone than to paclitaxel (P<0.002) and demostrated lower IC(50s) to patupilone (range 0.76-0.93nM) when compared to ovarian CS (range 1.9-3.4 nM, P<0.05). Higher levels of TUBB3 were detected in uterine CS cell lines and fresh frozen tissues when compared to ovarian CS (P<0.05). CONCLUSIONS: Uterine CS cell lines are significantly more sensitive than ovarian CS cell lines to patupilone versus paclitaxel. High expression of TUBB3 is associated with sensitivity to patupilone in primary CS cell lines and may act as a genetic marker to predict chemotherapy efficacy. Patupilone may represent a promising drug in the treatment of this subset of rare but highly aggressive gynecological tumors. Copyright © 2011. Published by Elsevier Inc.
carcinoma; patupilone; paclitaxel
10
info:eu-repo/semantics/article
262
Carrara, L; Guzzo, F; Roque, Dm; Bellone, Stefania; Emiliano, C; Sartori, Enrico; Pecorelli, Sergio; Schwartz, Pe; Rutherford, Tj; Gynecol Oncol, Sant...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/112912
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