چکیده (انگلیسی):

Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common malignant
brain tumor. Current therapies provide a median survival of 12–15 months after diagnosis,
due to the high recurrence rate. The failure of current therapies may be due to the presence,
within the tumor, of cells characterized by enhanced self-renewal capacity, multilineage
differentiation potential and elevated invasive behavior, called glioma stem cells (GSCs).
To evaluate the pharmacological efficacy of selected drugs on six GSC lines, we set up a
multiple drug responsivity assay based on the combined evaluation of cytomorphological
and functional parameters, including the analysis of polymorphic nuclei, mitotic index and
cell viability. In order to understand the real pharmacological efficacy of the tested drugs,
we assigned a specific drug responsivity score to each GSC line, integrating the data produced
by multiple assays. In this work we explored the antineoplastic effects of paclitaxel
(PTX), an inhibitor of microtubule depolymerization, utilized as standard treatment in several
cancers, and of valproic acid (VPA), an inhibitor of histone deacetylases (HDACs) with
multiple anticancer properties. We classified the six GSC lines as responsive or resistant
to these drugs, on the basis of their responsivity scores. This method can also be useful
to identify the best way to combine two or more drugs. In particular, we utilized the prodifferentiating
effect of VPA to improve the PTX effectiveness and we observed a significant
reduction of cell viability compared to single treatments.