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Molecular & Cellular Proteomics 5:35-42, 2006.
© 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

Analysis of Glioma Cell Platinum Response by Metacomparison of Two-dimensional Chromatographic Proteome Profiles^*

Christine Billecke, Imran Malik, Ashley Movsisyan, Syed Sulghani, Azita Sharif, Tom Mikkelsen, Nicholas P. Farrell^¶ and Oliver Bögler^,||,**

From the Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, Daedalus Software, Inc., Cambridge, Massachusetts 02138, the ^¶ Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23298, and the ^|| Brain Tumor Center and Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Successful clinical development of cancer treatments is aided by the development of molecular markers that allow the identification of patients likely to respond. In the case of broadly cytotoxic drugs, such as the multinuclear series of platinum chemotherapeutic agents that we are evaluating for the treatment of glioma, one route to marker identification is proteomic profiling. We are using the two-dimensional chromatography system, the ProteomeLab PF2D, to compare proteomic profiles of glioma cells in culture before and after drug treatment. The existing software tools allowed the rapid identification of peaks increased by treatment of a given drug as compared with control untreated cells. To compare across these pairs, we developed new software, called the MetaComparison Tool (MCT). The MCT uses the chromatographic characteristics of peaks as identifiers, an approach that was validated by mass spectrometry of two independent isolations of a peak, from cells that were treated with two different platinum compounds. The MCT made it possible to rapidly query whether a given peak responded to more than one treatment and so allowed the identification of peaks that were specific to a given drug. As a result, this analysis greatly reduced the list of peaks whose isolation and downstream analysis by mass spectrometry is warranted, accelerating the search for protein markers of response.

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