Abstract
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.
Keywords: Hypoxia, AQ4N, MALDI, ion mobility, mass spectrometry imaging
Current Analytical Chemistry
Title:Targeting of Hypoxia in AQ4N-treated Tumour Xenografts by MALDIIon Mobility Separation-Mass Spectrometry Imaging
Volume: 9 Issue: 2
Author(s): 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
Affiliation:
Keywords: Hypoxia, AQ4N, MALDI, ion mobility, mass spectrometry imaging
Abstract: 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.
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Djidja Marie-Claude, Francese Simona, Claude Emmanuelle, Loadman Paul, Sutton Chris, Shynder Steve, Cooper Patricia, H Patterson Laurence, A Carolan Vikki and R. Clench Malcolm, Targeting of Hypoxia in AQ4N-treated Tumour Xenografts by MALDIIon Mobility Separation-Mass Spectrometry Imaging, Current Analytical Chemistry 2013; 9 (2) . https://dx.doi.org/10.2174/1573411011309020007
DOI https://dx.doi.org/10.2174/1573411011309020007 |
Print ISSN 1573-4110 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6727 |
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