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- 저자 : Toshihide Nishimura (검색결과 1 건)
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Drug compound characterization by mass spectrometry imaging in cancer tissue
권호정,Johan Malm,김용효,Yutaka Sugihara,Bo Baldetorp,Charlotte Welinder,Ken-ichi Watanabe,Toshihide Nishimura,Gyo¨rgy Marko-Varga,Szilvia To¨ro¨k,Bala´zs Do¨me,´ kos Ve´gva´ri,Lena Gustavsson,Thomas E. Feh 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.9
MALDI mass spectrometry imaging (MSI)provides a technology platform that allows the accuratevisualization of unlabeled small molecules within the twodimensionalspaces of tissue samples. MSI has proven to bea powerful tool-box concept in the development of newdrugs. MSI allows unlabeled drug compounds and drugmetabolites to be detected and identified and quantifiedaccording to their mass-to-charge ratios (m/z) at high resolutionin complex tissue environments. Such drug characterizationin situ, by both spatial and temporal behaviorswithin tissue compartments, provide new understandings ofthe dynamic processes impacting drug uptake and metabolismat the local sites targeted by therapy. Further, MSIin combination with histology and immunohistochemistry,provides the added value of defining the context of cellbiology present at the sites of drug localization thus providinginvaluable information relating to treatment efficacy. In this report we provide mass spectrometry imagingdata within various cancers such as malignant melanoma inpatients administered with vemurafenib, a protein kinaseinhibitor that is targeting BRAF mutated proteins and thathas shown significant efficacy in restraining disease progression. We also provide an overview of other examplesof the new generation of targeted drugs, and demonstratethe data on personalized medicine drugs localization withintumor compartments within in vivo models. In these cancermodels we provide detailed data on drug and target proteinco-localization of YCG185 and sunitinib. These drugs aretargeting VEGFR2 within the angiogenesis mechanism. Our ability to resolve drug uptake at targeted sites ofdirected therapy provides important opportunities forincreasing our understanding about the mode of action ofdrug activity within the environment of disease.
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