Proteomics in Pathology: The Special Issue

Longuespée, Rémi; Casadonte, Rita; Schwamborn, Kristina; Kriegsmann, Mark

doi:10.1002/prca.201800167

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…Given the benefits and long practice of FFPE, there are hundreds of thousands of samples available, complete with clinical outcomes, even for rare diseases. The downside being that in their current state, they limit the amount of chemical information attainable by MSI 7 or vibrational spectroscopy. 8 Yet, with the allure of accessing libraries of unique samples, efforts have been made to access some of this molecular information with both vibrational spectroscopy and MSI and FFPE samples are widely used for protein, 9 glycan, 10 and some lipid 11 analyses.…”

Section: Pre-analytical Factorsmentioning

confidence: 99%

Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review

et al. 2020

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Section: Pre-analytical Factorsmentioning

confidence: 99%

Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review

et al. 2020

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“…Innovative mass spectrometry-based applications are beginning to address challenges in clinics and the healthcare sector, such as the use of targeted proteomics to characterize noninvasive liquid biopsies [46] or the so called iKnife, enabling surgeons to identify cancerous tissue in real time [47, 48]. Mass spectrometry is becoming increasingly applicable in a clinical setting [49, 50]. FFPE sections are a valuable source for mass spectrometry-based diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Histo-molecular differentiation of renal cancer subtypes by mass spectrometry imaging and rapid proteome profiling of formalin-fixed paraffin-embedded tumor tissue sections

Möginger

Marcussen

Jensen

2020

Preprint

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Background: Pathology assessment and differentiation of renal cancer types is challenging due to overlapping histological features of benign and malignant tumors, necessitating highlevel expertise. Mass spectrometry (MS) is an emerging tool for tumor classification of clinical tissue sections by spatial histo-molecular imaging or quantitative microproteomics profiling. Results: We applied MALDI MS imaging (MSI) and LC-MS/MS-based microproteomics technologies to analyze and classify renal oncocytoma (RO, n=11), clear cell renal cell carcinoma (ccRCC, n=12) and chromophobe renal cell carcinoma (CRCC, n=5). Both methods distinguished ccRCC, RO and CCRC with high accuracy in cross-validation experiments (MSI: 93-95%, LC-MS/MS: 100%). Significance: This integrated strategy combining MSI and rapid proteome profiling by LC-MS/MS reveals molecular features of tumor sections and enables cancer subtype classification. Mass spectrometry is a promising complementary approach to current pathological technologies for precise digitized diagnosis of diseases.

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“…High-sensitivity devices would allow quantifying drugs in cells using the MALDI imaging mode The link between on-surface sampling and liquid handling is laser microdissection (LMD), which allows for the precise collection of solid samples deposited on surfaces. 135,139 LMD allows for the collection of pure cell populations from tissues bearing large cellular heterogeneity. It has mostly been applied for omics purposes 140,141 but was also used for the extraction of drugs from tissue regions of interest.…”

Section: Therapies Applied To Circulating Cells: Ideal Models For Pmentioning

confidence: 99%

“…The link between on‐surface sampling and liquid handling is laser microdissection (LMD), which allows for the precise collection of solid samples deposited on surfaces 135,139 . LMD allows for the collection of pure cell populations from tissues bearing large cellular heterogeneity.…”

Section: Down‐scaling Sample Collection and Analyses At The Drug's Cementioning

confidence: 99%

Approaching sites of action of drugs in clinical pharmacology: New analytical options and their challenges

Longuespée

Theile

Fresnais

et al. 2020

Brit J Clinical Pharma

Self Cite

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Clinical pharmacology is an important discipline for drug development aiming to define pharmacokinetics (PK), pharmacodynamics (PD) and optimum exposure to drugs, i.e. the concentration-response relationship and its modulators. For this purpose, information on drug concentrations at the anatomical, cellular and molecular sites of action is particularly valuable. In pharmacological assays, the limited accessibility of target cells in readily available samples (i.e. blood) often hampers mass spectrometry-based monitoring of the absolute quantity of a compound and the determination of its molecular action at the cellular level. Recently, new sample collection methods have been developed for the specific capture of rare circulating cells, especially for the diagnosis of circulating tumour cells. In parallel, new advances and developments in mass spectrometric instrumentation now allow analyses to be scaled down to the cellular level. Together, these developments may permit the monitoring of minute drug quantities and show their effect at the cellular level. In turn, such PK/PD associations on a cellular level would not only enrich our pharmacological knowledge of a given compound but also expand the basis for PK/PD simulations. In this review, we describe novel concepts supporting clinical pharmacology at the anatomical, cellular and molecular sites of action, and highlight the new challenges in mass spectrometry-based monitoring. Moreover, we present methods to tackle these challenges and define future needs. K E Y W O R D S clinical pharmacology, mass spectrometry, personalized medicine, review, sites of action 1 | INTRODUCTION Clinical pharmacology studies the relevant parameters of drug fate (pharmacokinetics, PK) and efficacy (pharmacodynamics, PD) in humans in order to establish the dose-response and concentrationresponse relationship. It also defines intraindividual and interindividual modulators of these relationships, leading to different effectiveness, safety and dose requirements. Monitoring drug concentrations and effects is therefore of considerable importance during drug development, starting with the very first clinical trials. 1 Clinical pharmacology clarifies mechanisms of both beneficial and adverse drug effects in order to get closer to drug effectiveness monitoring. A drug's site of action can be defined at different scales: anatomical (the compartment the drug has to reach, e.g. tissues), cellular (the

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Proteomics in Pathology: The Special Issue

Cited by 9 publications

References 48 publications

Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review

Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review

Histo-molecular differentiation of renal cancer subtypes by mass spectrometry imaging and rapid proteome profiling of formalin-fixed paraffin-embedded tumor tissue sections

Approaching sites of action of drugs in clinical pharmacology: New analytical options and their challenges

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