In vitro synergistic cytotoxicity of gemcitabine and pemetrexed and pharmacogenetic evaluation of response to gemcitabine in bladder cancer patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-08

AUTHORS

V Mey, E Giovannetti, F De Braud, S Nannizzi, G Curigliano, F Verweij, O De Cobelli, S Pece, M Del Tacca, R Danesi

ABSTRACT

The present study was performed to investigate the capability of gemcitabine and pemetrexed to synergistically interact with respect to cytotoxicity and apoptosis in T24 and J82 bladder cancer cells, and to establish a correlation between drug activity and gene expression of selected genes in tumour samples. The interaction between gemcitabine and pemetrexed was synergistic; indeed, pemetrexed favoured gemcitabine cytotoxicity by increasing cellular population in S-phase, reducing Akt phosphorylation as well as by inducing the expression of a major gemcitabine uptake system, the human equilibrative nucleoside transporter-1 (hENT1), and the key activating enzyme deoxycytidine kinase (dCK) in both cell lines. Bladder tumour specimens showed an heterogeneous gene expression pattern and patients with higher levels of dCK and hENT1 had better response. Moreover, human nucleoside concentrative transporter-1 was detectable only in 3/12 patients, two of whom presented a complete response to gemcitabine. These data provide evidence that the chemotherapeutic activity of the combination of gemcitabine and pemetrexed is synergistic against bladder cancer cells in vitro and that the assessment of the expression of genes involved in gemcitabine uptake and activation might be a possible determinant of bladder cancer response and may represent a new tool for treatment optimization. More... »

PAGES

6603242

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6603242

DOI

http://dx.doi.org/10.1038/sj.bjc.6603242

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031227779

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16868547


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