MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS
MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS SARA L. FRAPPIER Dissertation under the direction of Professor Richard M. Caprioli A protocol has been developed to implement small molecule quantitation with MALDI Imaging MS direc...
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ndltd-VANDERBILT-oai-VANDERBILTETD-etd-03282011-1038362013-01-08T17:16:47Z MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS Frappier, Sara Lynn Chemistry MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS SARA L. FRAPPIER Dissertation under the direction of Professor Richard M. Caprioli A protocol has been developed to implement small molecule quantitation with MALDI Imaging MS directly from tissue sections. This protocol allows for MALDI based imaging technologies to correlate absolute drug concentration with pharmacological response in tissues while still maintaining spatial information in rapid, high-throughput molecularly specific experiments. The quantitation protocol has been applied to the investigation of two therapies under investigation for the treatment of Glioblastomas (brain tumors of glial cell origin) to determine the quantities of compound that reach the brain and tumor areas in mouse models. Imaging experiments performed by MALDI were able to provide the individual, label-free temporal distributions of IMAT and CYC from brain tissue sections with high sensitivity and reproducibility. Highly-accurate absolute quantities of each compound were also obtained directly from tissue sections without the need for homogenization or extraction procedures. Using the calculated drug concentrations of IMAT and CYC in conjunction with standard MALDI TOF imaging, it was possible to study the proteome affects that the drug presence had on primary brain tumor xenografts in mice. MALDI Imaging MS proved to be an invaluable tool to rapidly and reproducibly relate the tissue distribution of the IMAT and CYC to the observed pharmacological response within the same tissue sample while maintaining spatial resolution. Altered proteins were identified and can contribute to an improved understanding of the IMAT and CYC mechanisms of action as well as help gain a deeper understanding of the mechanisms involved in primary brain tumor function. Richard M. Caprioli Michael K. Cooper Brian.O. Bachmann Reid C. Thompson VANDERBILT 2011-04-14 text application/pdf http://etd.library.vanderbilt.edu/available/etd-03282011-103836/ http://etd.library.vanderbilt.edu/available/etd-03282011-103836/ en unrestricted I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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Chemistry Frappier, Sara Lynn MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS |
description |
MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS
SARA L. FRAPPIER
Dissertation under the direction of Professor Richard M. Caprioli
A protocol has been developed to implement small molecule quantitation with MALDI Imaging MS directly from tissue sections. This protocol allows for MALDI based imaging technologies to correlate absolute drug concentration with pharmacological response in tissues while still maintaining spatial information in rapid, high-throughput molecularly specific experiments. The quantitation protocol has been applied to the investigation of two therapies under investigation for the treatment of Glioblastomas (brain tumors of glial cell origin) to determine the quantities of compound that reach the brain and tumor areas in mouse models. Imaging experiments performed by MALDI were able to provide the individual, label-free temporal distributions of IMAT and CYC from brain tissue sections with high sensitivity and reproducibility. Highly-accurate absolute quantities of each compound were also obtained directly from tissue sections without the need for homogenization or extraction procedures. Using the calculated drug concentrations of IMAT and CYC in conjunction with standard MALDI TOF imaging, it was possible to study the proteome affects that the drug presence had on primary brain tumor xenografts in mice. MALDI Imaging MS proved to be an invaluable tool to rapidly and reproducibly relate the tissue distribution of the IMAT and CYC to the observed pharmacological response within the same tissue sample while maintaining spatial resolution. Altered proteins were identified and can contribute to an improved understanding of the IMAT and CYC mechanisms of action as well as help gain a deeper understanding of the mechanisms involved in primary brain tumor function.
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author2 |
Richard M. Caprioli |
author_facet |
Richard M. Caprioli Frappier, Sara Lynn |
author |
Frappier, Sara Lynn |
author_sort |
Frappier, Sara Lynn |
title |
MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS |
title_short |
MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS |
title_full |
MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS |
title_fullStr |
MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS |
title_full_unstemmed |
MALDI IMAGING MASS SPECTROMETRY FOR SMALL MOLECULE QUANTITATION AND EVALUATION FOR MARKERS OF DRUG RESPONSE IN GLIOMAS |
title_sort |
maldi imaging mass spectrometry for small molecule quantitation and evaluation for markers of drug response in gliomas |
publisher |
VANDERBILT |
publishDate |
2011 |
url |
http://etd.library.vanderbilt.edu/available/etd-03282011-103836/ |
work_keys_str_mv |
AT frappiersaralynn maldiimagingmassspectrometryforsmallmoleculequantitationandevaluationformarkersofdrugresponseingliomas |
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1716570213080629248 |