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KMID : 0043320150380091718
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Archives of Pharmacal Research
2015 Volume.38 No. 9 p.1718 ~ p.1727
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Drug compound characterization by mass spectrometry imaging in cancer tissue
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Kwon Ho-Jeong
Kim Yong-Hyo
Sugihara Yutaka
Baldetorp Bo
Welinder Charlotte
Watanabe Ken ichi
Nishimura Toshihide
Malm Johan
Torok Szilvia
Dome Balazs
Vegvari Akos
Gustavsson Lena
Fehniger Thomas E.
Marko Varga Gyorgy
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Abstract
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MALDI mass spectrometry imaging (MSI) provides a technology platform that allows the accurate visualization of unlabeled small molecules within the two-dimensional spaces of tissue samples. MSI has proven to be a powerful tool-box concept in the development of new drugs. MSI allows unlabeled drug compounds and drug metabolites to be detected and identified and quantified according to their mass-to-charge ratios (m/z) at high resolution in complex tissue environments. Such drug characterization in situ, by both spatial and temporal behaviors within tissue compartments, provide new understandings of the dynamic processes impacting drug uptake and metabolism at the local sites targeted by therapy. Further, MSI in combination with histology and immunohistochemistry, provides the added value of defining the context of cell biology present at the sites of drug localization thus providing invaluable information relating to treatment efficacy. In this report we provide mass spectrometry imaging data within various cancers such as malignant melanoma in patients administered with vemurafenib, a protein kinase inhibitor that is targeting BRAF mutated proteins and that has shown significant efficacy in restraining disease progression. We also provide an overview of other examples of the new generation of targeted drugs, and demonstrate the data on personalized medicine drugs localization within tumor compartments within in vivo models. In these cancer models we provide detailed data on drug and target protein co-localization of YCG185 and sunitinib. These drugs are targeting VEGFR2 within the angiogenesis mechanism. Our ability to resolve drug uptake at targeted sites of directed therapy provides important opportunities for increasing our understanding about the mode of action of drug activity within the environment of disease.
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KEYWORD
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Mass spectrometry imaging, Protein sequence, Drug compound, Cancer, Malignant melanoma
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