Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using Tumor Explants for Imaging Mass Spectrometry Visualization of Unlabeled Peptides and Small Molecules.

ABSTRACT: Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) imaging mass spectrometry has emerged as a powerful, label-free technique to visualize penetration of small molecules in vivo and in vitro, including in 3D cell culture spheroids; however, some spheroids do not grow sufficiently large to provide enough area for imaging mass spectrometry. Here, we describe an ex vivo method for visualizing unlabeled peptides and small molecules in tumor explants, which can be divided into pieces of desired size, thus circumventing the size limitations of many spheroids. As proof-of-concept, a small molecule drug (4-hydroxytamoxifen), as well as a peptide drug (cyclosporin A) and peptide chemical probe, can be visualized after in vitro incubation with tumor explants so that this technique may provide a solution to robing cell penetration by unlabeled peptides.

SUBMITTER: David BP

PROVIDER: S-EPMC6047048 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Using Tumor Explants for Imaging Mass Spectrometry Visualization of Unlabeled Peptides and Small Molecules.

David Brian P BP Dubrovskyi Oleksii O Speltz Thomas E TE Wolff Jeremy J JJ Frasor Jonna J Sanchez Laura M LM Moore Terry W TW

ACS medicinal chemistry letters 20180517 7

Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) imaging mass spectrometry has emerged as a powerful, label-free technique to visualize penetration of small molecules in vivo and in vitro, including in 3D cell culture spheroids; however, some spheroids do not grow sufficiently large to provide enough area for imaging mass spectrometry. Here, we describe an ex vivo method for visualizing unlabeled peptides and small molecules in tumor explants, which can ...[more]

PMID: 30034616

Similar Datasets

Matrix Selection for the Visualization of Small Molecules and Lipids in Brain Tumors Using Untargeted MALDI-TOF Mass Spectrometry Imaging

Project description:Matrix-assisted laser desorption/ionization mass spectrometry imaging allows for the study of metabolic activity in the tumor microenvironment of brain cancers. The detectable metabolites within these tumors are contingent upon the choice of matrix, deposition technique, and polarity setting. In this study, we compared the performance of three different matrices, two deposition techniques, and the use of positive and negative polarity in two different brain cancer types and across two species. Optimal combinations were confirmed by a comparative analysis of lipid and small-molecule abundance by using liquid chromatography-mass spectrometry and RNA sequencing to assess differential metabolites and enzymes between normal and tumor regions. Our findings indicate that in the tumor-bearing brain, the recrystallized α-cyano-4-hydroxycinnamic acid matrix with positive polarity offered superior performance for both detected metabolites and consistency with other techniques. Beyond these implications for brain cancer, our work establishes a workflow to identify optimal matrices for spatial metabolomics studies.

2024-10-09 | GSE279139 | GEO

Matrix Selection for the Visualization of Small Molecules and Lipids in Brain Tumors Using Untargeted MALDI-TOF Mass Spectrometry Imaging.

| S-EPMC10673325 | biostudies-literature

Mass Spectrometry-Based Visualization of Molecules Associated with Human Habitats.

Project description:The cars we drive, the homes we live in, the restaurants we visit, and the laboratories and offices we work in are all a part of the modern human habitat. Remarkably, little is known about the diversity of chemicals present in these environments and to what degree molecules from our bodies influence the built environment that surrounds us and vice versa. We therefore set out to visualize the chemical diversity of five built human habitats together with their occupants, to provide a snapshot of the various molecules to which humans are exposed on a daily basis. The molecular inventory was obtained through untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of samples from each human habitat and from the people that occupy those habitats. Mapping MS-derived data onto 3D models of the environments showed that frequently touched surfaces, such as handles (e.g., door, bicycle), resemble the molecular fingerprint of the human skin more closely than other surfaces that are less frequently in direct contact with humans (e.g., wall, bicycle frame). Approximately 50% of the MS/MS spectra detected were shared between people and the environment. Personal care products, plasticizers, cleaning supplies, food, food additives, and even medications that were found to be a part of the human habitat. The annotations indicate that significant transfer of chemicals takes place between us and our built environment. The workflows applied here will lay the foundation for future studies of molecular distributions in medical, forensic, architectural, space exploration, and environmental applications.

| S-EPMC6326777 | biostudies-literature

MolDiscovery: learning mass spectrometry fragmentation of small molecules.

Project description:Identification of small molecules is a critical task in various areas of life science. Recent advances in mass spectrometry have enabled the collection of tandem mass spectra of small molecules from hundreds of thousands of environments. To identify which molecules are present in a sample, one can search mass spectra collected from the sample against millions of molecular structures in small molecule databases. The existing approaches are based on chemistry domain knowledge, and they fail to explain many of the peaks in mass spectra of small molecules. Here, we present molDiscovery, a mass spectral database search method that improves both efficiency and accuracy of small molecule identification by learning a probabilistic model to match small molecules with their mass spectra. A search of over 8 million spectra from the Global Natural Product Social molecular networking infrastructure shows that molDiscovery correctly identify six times more unique small molecules than previous methods.

| S-EPMC8211649 | biostudies-literature

Matrix Selection for the Visualization of Small Molecules and Lipids in Brain Tumors Using Untargeted MALDI-TOF Mass Spectrometry Imaging

Project description:Matrix Selection for the Visualization of Small Molecules and Lipids in Brain Tumors Using Untargeted MALDI-TOF Mass Spectrometry Imaging

| PRJNA1170957 | ENA

Detection and visualization of communities in mass spectrometry imaging data.

Project description:BackgroundThe spatial distribution and colocalization of functionally related metabolites is analysed in order to investigate the spatial (and functional) aspects of molecular networks. We propose to consider community detection for the analysis of m/z-images to group molecules with correlative spatial distribution into communities so they hint at functional networks or pathway activity. To detect communities, we investigate a spectral approach by optimizing the modularity measure. We present an analysis pipeline and an online interactive visualization tool to facilitate explorative analysis of the results. The approach is illustrated with synthetical benchmark data and two real world data sets (barley seed and glioblastoma section).ResultsFor the barley sample data set, our approach is able to reproduce the findings of a previous work that identified groups of molecules with distributions that correlate with anatomical structures of the barley seed. The analysis of glioblastoma section data revealed that some molecular compositions are locally focused, indicating the existence of a meaningful separation in at least two areas. This result is in line with the prior histological knowledge. In addition to confirming prior findings, the resulting graph structures revealed new subcommunities of m/z-images (i.e. metabolites) with more detailed distribution patterns. Another result of our work is the development of an interactive webtool called GRINE (Analysis of GRaph mapped Image Data NEtworks).ConclusionsThe proposed method was successfully applied to identify molecular communities of laterally co-localized molecules. For both application examples, the detected communities showed inherent substructures that could easily be investigated with the proposed visualization tool. This shows the potential of this approach as a complementary addition to pixel clustering methods.

| S-EPMC6549267 | biostudies-literature

Advances in structure elucidation of small molecules using mass spectrometry.

Project description:The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12566-010-0015-9) contains supplementary material, which is available to authorized users.

| S-EPMC3015162 | biostudies-literature

Versatile, sensitive liquid chromatography mass spectrometry - Implementation of 10??m OT columns suitable for small molecules, peptides and proteins.

Project description:We have designed a versatile and sensitive liquid chromatographic (LC) system, featuring a monolithic trap column and a very narrow (10??m ID) fused silica open tubular liquid chromatography (OTLC) separation column functionalized with C18-groups, for separating a wide range of molecules (from small metabolites to intact proteins). Compared to today's capillary/nanoLC approaches, our system provides significantly enhanced sensitivity (up to several orders) with matching or improved separation efficiency, and highly repeatable chromatographic performance. The chemical properties of the trap column and the analytical column were fine-tuned to obtain practical sample loading capacities (above 2??g), an earlier bottleneck of OTLC. Using the OTLC system (combined with Orbitrap mass spectrometry), we could perform targeted metabolomics of sub-?g amounts of exosomes with 25 attogram detection limit of a breast cancer-related hydroxylated cholesterol. With the same set-up, sensitive bottom-up proteomics (targeted and untargeted) was possible, and high-resolving intact protein analysis. In contrast to state-of-the-art packed columns, our platform performs chromatography with very little dilution and is "fit-for-all", well suited for comprehensive analysis of limited samples, and has potential as a tool for challenges in diagnostics.

| S-EPMC5126632 | biostudies-literature

Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry–based imaging

Project description:Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation. Locked nucleic acid (LNA) modified NCL-APT administered subcutaneously (s.c.) near tumor or intraperitoneally (i.p.) in Y79 xenografted nude mice resulted in 26 and 65% of tumor growth inhibition, respectively. Downregulation of inhibitor of apoptosis proteins, tumor miRNA-18a, altered serum cytokines, and serum miRNA-18a levels were observed upon NCL-APT treatment. Desorption electrospray ionization mass spectrometry (DESI MS)-based imaging of cell lines and tumor tissues revealed changes in phosphatidylcholines levels upon treatment. Thus, our study provides proof of concept illustrating NCL-APT-based targeted therapeutic strategy and use of DESI MS-based lipid imaging in monitoring therapeutic responses in RB.

2016-11-15 | GSE89818 | GEO

Evaluation of Small Molecule Drug Uptake in Patient-Derived Prostate Cancer Explants by Mass Spectrometry.

Project description:Patient-derived explant (PDE) culture of solid tumors is increasingly being applied to preclinical evaluation of novel therapeutics and for biomarker discovery. In this technique, treatments are added to culture medium and penetrate the tissue via a gelatin sponge scaffold. However, the penetration profile and final concentrations of small molecule drugs achieved have not been determined to date. Here, we determined the extent of absorption of the clinical androgen receptor antagonist, enzalutamide, into prostate PDEs, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matrix-assisted laser/desorption ionisation (MALDI) mass spectrometry imaging (MSI). In a cohort of 11 PDE tissues from eight individual patients, LC-MS/MS quantification of PDE homogenates confirmed enzalutamide (10?µM) uptake by all PDEs, which reached maximal average tissue concentration of 0.24-0.50?ng/µg protein after 48?h culture. Time dependent uptake of enzalutamide (50?µM) in PDEs was visualized using MALDI MSI over 24-48?h, with complete penetration throughout tissues evident by 6?h of culture. Drug signal intensity was not homogeneous throughout the tissues but had areas of markedly high signal that corresponded to drug target (androgen receptor)-rich epithelial regions of tissue. In conclusion, application of MS-based drug quantification and visualization in PDEs, and potentially other 3-dimensional model systems, can provide a more robust basis for experimental study design and interpretation of pharmacodynamic data.

| S-EPMC6802206 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data