Document Detail


Differential in vitro sensitivity to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas cell lines is linked to tubulin-beta-III expression.
MedLine Citation:
PMID:  22209775     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Luisa Carrara; Federica Guzzo; Dana M Roque; Stefania Bellone; Cocco Emiliano; Enrico Sartori; Sergio Pecorelli; Peter E Schwartz; Thomas J Rutherford; Alessandro D Santin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-29
Journal Detail:
Title:  Gynecologic oncology     Volume:  -     ISSN:  1095-6859     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Division of Gynecologic Oncology, University of Brescia, Brescia, Italy.
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