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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 2/2011

01-02-2011 | Original Article

In vitro anti-mesothelioma activity of cisplatin–gemcitabine combinations: evidence for sequence-dependent effects

Authors: Ilaria Zanellato, Carla Doriana Boidi, Guido Lingua, Pier-Giacomo Betta, Sara Orecchia, Elena Monti, Domenico Osella

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2011

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Abstract

Purpose

The present study addresses the optimization of gemcitabine–cisplatin protocols currently adopted in the clinical management of malignant pleural mesothelioma (MPM), using cell lines derived from different histological subtypes of MPM as an in vitro model.

Methods

MPM cell lines were exposed either to single drugs or to their combinations, using a fixed dose ratio. Possible mechanisms for synergistic interactions were investigated by cell cycle analysis, western blot analysis of p53 phosphorylation status, and neutral comet assay to detect double strand breaks.

Results

Four-hour pre-treatment with gemcitabine followed by 68-h exposure to cisplatin was found to exert synergistic activity in both epithelioid and sarcomatoid MPM subtypes, inducing a strong S-phase arrest that correlated with accumulation of double-strand breaks (DSBs).

Conclusion

The antiproliferative effects of the gemcitabine/cisplatin combination in mesothelioma cells can be maximized by pre-treatment with gemcitabine, suggesting that this drug increases cisplatin-induced DSBs by inhibiting DNA adduct repair.
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Metadata
Title
In vitro anti-mesothelioma activity of cisplatin–gemcitabine combinations: evidence for sequence-dependent effects
Authors
Ilaria Zanellato
Carla Doriana Boidi
Guido Lingua
Pier-Giacomo Betta
Sara Orecchia
Elena Monti
Domenico Osella
Publication date
01-02-2011
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-010-1314-0

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