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@proceedings{1216202, author = {Manca, Matteo and Pivetta, Tiziana and Isaia, Franco and Trudu, Federica and Perra, Daniela and Spiga, Francesca and Amato, Filippo}, booktitle = {XII FISV Congress 2012}, keywords = {artificial neural networks; synergism; experimental design}, language = {eng}, title = {Synergistic cytotoxicity of copper(II) complexes in combination with cisplatin: an application of artificial neural networks and experimental design}, year = {2012} }
TY - CONF ID - 1216202 AU - Manca, Matteo - Pivetta, Tiziana - Isaia, Franco - Trudu, Federica - Perra, Daniela - Spiga, Francesca - Amato, Filippo PY - 2012 TI - Synergistic cytotoxicity of copper(II) complexes in combination with cisplatin: an application of artificial neural networks and experimental design KW - artificial neural networks KW - synergism KW - experimental design N2 - Cisplatin is highly effective in treating a variety of cancers [ 1] but both inherited and acquired tumoral cell resistance seriously limits its applications [2]. Anticancer drugs are widely used in suitable combinations in order to improve their action [3]. In the cell, associations of two or more drugs may exhibit synergistic, antagonistic or addictive effects. Synergistic, antagonistic or additive type of interaction occurs when the cytotoxicity of the drug combination is respectively greater, lower, or equal to the sum of the cytotoxicity of individual drugs. Complexes of copper(II) with 1,10-ortho-phenanthroline (phen) are also endowed with cytotoxic and antitumoral effects being capable of cleaving DNA and improving nuclease activity [4]. Recently, we prepared a series of new copper(II) complexes, containing two phen units and N,N’-substituted-imidazolidine-2-thione as auxiliary ligands [5]; these compounds are characterized by a high chemical stability coupled with a high cytotoxic activity against mouse neuroblastoma as well as human hematologic and solid tumor-derived cell lines [6]. In this work we propose a new approach to search for optimal combination of the two compounds for which maximum synergy is observed, by using Artificial Neural Networks (ANNs) and the Experimental Design (ED). The studied compounds are reported in Table 1. We prepared 40 mixtures of copper complex and cisplatin and measured the corresponding cytotoxicity against CCRF-CEM T-leukaemia cell lines. A neural network was used to model experiments and then to predict the cytotoxicity values on the whole working space. The values so obtained were corrected for the pure additive effect, putting in evidence the synergistic effect. In Figure 1a and 1b the calculated and corrected response surfaces for the C1-cisplatin system respectively, are shown. ED-ANN can be considered as a new, efficient and fast method to search for synergy of drug mixtures and/or even for new drugs. ER -
MANCA, Matteo, Tiziana PIVETTA, Franco ISAIA, Federica TRUDU, Daniela PERRA, Francesca SPIGA and Filippo AMATO. Synergistic cytotoxicity of copper(II) complexes in combination with cisplatin: an application of artificial neural networks and experimental design. In \textit{XII FISV Congress 2012}. 2012.
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