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Targeting of Hypoxia in AQ4N-treated Tumour Xenografts by MALDIIon Mobility Separation-Mass Spectrometry Imaging

[ Vol. 9 , Issue. 2 ]


Marie-Claude Djidja, Simona Francese, Emmanuelle Claude, Paul Loadman, Chris Sutton, Steve Shynder, Patricia Cooper, Laurence H Patterson, Vikki A Carolan and Malcolm R. Clench   Pages 212 - 225 ( 14 )


Hypoxia is a common feature observed in solid tumours. It is a target of interest in oncology as it has been found to be closely associated with tumour progression, metastasis and aggressiveness and confers resistance to a variety of chemotherapeutic agents as well as radiotherapy. AQ4N, also known as banoxatrone or 1,4-bis-[2-(dimethylamino-Noxide) ethyl]amino-5,8-dihydroxyanthracene-9,10-dione is a very promising bioreductive prodrug. This paper, describes an application of MALDI-MSI combined with ion mobility separation and an "on-tissue" bottom up proteomic strategy to obtain proteomic data from AQ4N dosed tumour xenograft tissue sections. These data are then correlated with the drug distribution determined also using MALDI-ion mobility separation-mass spectrometry imaging (MALDI-IMS-MSI). PCA-DA and OPLS-DA have been used to compare treated and untreated xenografts and of note is the marked increase in expression of Histone H3.


Hypoxia, AQ4N, MALDI, ion mobility, mass spectrometry imaging


Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield UK S1 1WB.

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