Biomedical subjects

Michelle L Reyzer

Publications and source records attributed to Michelle L Reyzer.

7 recordsLinked to original sources

PubMed2006

MALDI-MS-based imaging of small molecules and proteins in tissues.

The direct analysis of tissues using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) enables both endogenous and exogenous compounds present in tissues to be detected with molecular specificity while maintaining their spatial orientation. This unique combination, coupled with excellent sensitivity and rapid analysis time, presents many potential advantages to a wide range of applications in diverse biological fields. Recent advances have shown how the technique can be applied to cancer research, neuroscience and pharmaceutical development. Examples include the use of unique protein profiles to classify human tumor tissues and predict patient outcomes, the discovery of protein changes in mouse cerebellum as a function of development, and the two-dimensional visualization of the distribution of a drug and first-pass metabolites in rat whole-body sections.

Animals↗

PubMed2005

Imaging mass spectrometry: principles and potentials.

Direct tissue profiling and imaging mass spectrometry (MS) allow for detailed mapping of the complex protein pattern across a tissue sample. Utilization of these tools provides spatial information across a tissue section for target protein expression and can be used to correlate changes in expression levels with specific disease states or drug response. Protein patterns can be directly correlated to known histological regions within the tissue, allowing for the direct monitoring of proteins specific for morphological regions within a tissue sample. Profiling and imaging MS have been used to characterize multiple tissues, including human gliomas and lung cancers, as well as tumor response to specific therapeutics, suggesting the use of proteomic information in assessing disease progression as well as predicting patient response to specific treatments. This article discusses both the technology and methods involved in analyzing proteins directly from tissue samples as well as several MS applications, including profiling human tumors, characterizing protein differences between tumor grades, and monitoring protein changes due to drug therapy.

Adenocarcinoma↗

PubMed2004

Early changes in protein expression detected by mass spectrometry predict tumor response to molecular therapeutics.

Biomarkers that predict therapeutic response are essential for the development of anticancer therapies. We have used matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to directly analyze protein profiles in mouse mammary tumor virus/HER2 transgenic mouse frozen tumor sections after treatment with the erbB receptor inhibitors OSI-774 and Herceptin. Inhibition of tumor cell proliferation and induction of apoptosis and tumor reduction were predicted by a >80% reduction in thymosin beta4 and ubiquitin levels that were detectable after 16 hours of a single drug dose before any evidence of in situ cellular activity. These effects were time- and dose-dependent, and their spatial distribution in the tumor correlated with that of the small-molecule inhibitor OSI-774. In addition, they predicted for therapeutic synergy of OSI-774 and Herceptin as well as for drug resistance. These results suggest that drug-induced early proteomic changes as measured by MALDI-MS can be used to predict the therapeutic response to established and novel therapies.

Amino Acid Sequence↗

PubMed2003

Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation.

Practical guidelines for the preparation of tissue sections for direct analysis by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry are presented. Techniques for proper sample handling including tissue storage, sectioning and mounting are described. Emphasis is placed on optimizing matrix parameters such as the type of matrix molecule used, matrix concentration, and solvent composition. Several different techniques for matrix application are illustrated. Optimal instrument parameters and the necessity for advanced data analysis approaches with regards to direct tissue analysis are also discussed.

Animals↗

PubMed2003

Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used to directly analyze and image pharmaceutical compounds in intact tissue. The anti-tumor drug SCH 226374 was unambiguously determined in mouse tumor tissue using MALDI-QqTOFMS (QSTAR) by monitoring the dissociation of the protonated drug at m/z 695.4 to its predominant fragment at m/z 228.1. A second drug, compound A, was detected in slices of rat brain tissue following oral administration with doses ranging from 1-25 mg/kg. Quantitation of compound A from whole brain homogenates using routine high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) procedures revealed that concentrations of the drug in whole brain varied from a low of 24 ng/g to a high of 1790 ng/g. The drug candidate was successfully detected by MALDI-QqTOF in samples from each dose, covering a range of approximately two orders of magnitude. In addition, good correlation was observed between the MALDI-QqTOFMS intensities at each dose with the HPLC/MS/MS results. Thus the MALDI-MS response is proportional to the amount of drug in tissue. Custom software was developed to facilitate the imaging of small molecules in tissue using the MALDI-QqTOF mass spectrometer. Images revealing the spatial localization of SCH 226374 in tumor tissue and compound A in brain tissue were acquired.

Animals↗

PubMed2003

Profiling and imaging proteins in the mouse epididymis by imaging mass spectrometry.

Different aspects of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) have been used as discovery tools to obtain global and time-correlated information on the local proteomic composition of the sexually mature mouse epididymis from both qualitative and semiquantitative points of view. Tissue sections and laser captured microdissected cells and secretory products were analyzed by MALDI-MS and from the recovered protein profiles, over 400 different proteins were monitored. Over 50 of these, some of which have been identified, displayed regionalized behavior from caput to cauda within the epididymis. Combining the information obtained from high-resolution imaging mass spectrometry and laser captured microdissection experiments, numerous proteins were localized within the epididymis at the cellular level. Furthermore, from the signal intensities observed in the different protein profiles organized in space, semiquantitative information for each protein was obtained.

Amino Acid Sequence↗

PubMedDate not supplied

MALDI mass spectrometry for direct tissue analysis: a new tool for biomarker discovery.

The direct analysis of tissue sections by MALDI mass spectrometry holds tremendous potential for biomarker discovery. This technology routinely allows many hundreds of proteins to be detected over a mass range of approximately 2000-70 000 Da while maintaining the spatial localization of the proteins detected. This technology has been applied to a wide range of tissue samples, including human glioma tissue and human lung tumor tissue. In many cases, biostatistical analyses of the resulting protein profiles revealed patterns that correlated with disease state and/or clinical endpoints. This work serves as a review of recent applications and summarizes the current state of technology.

Animals↗