Bioinformatic Analysis of Data Generated from MALDI Mass Spectrometry for Biomarker Discovery

Author(s):  
Zengyou He ◽  
Robert Z. Qi ◽  
Weichuan Yu
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shadrack M. Mutuku ◽  
Paul J. Trim ◽  
Bala K. Prabhala ◽  
Swati Irani ◽  
Kayla L. Bremert ◽  
...  

Abstract 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.


2018 ◽  
Author(s):  
Shazia Khan ◽  
Diego F Cobice ◽  
Dawn EW Livingstone ◽  
C Logan Mackay ◽  
Scott P Webster ◽  
...  

2020 ◽  
Vol 75 (14) ◽  
pp. 1749-1757
Author(s):  
E. A. Anikeenko ◽  
E. N. Rakhmatullina ◽  
D. I. Falev ◽  
O. Yu. Khoroshev ◽  
N. V. Ul’yanovskii ◽  
...  

Author(s):  
Riccardo Zecchi ◽  
Pietro Franceschi ◽  
Laura Tigli ◽  
Davide Amidani ◽  
Chiara Catozzi ◽  
...  

AbstractCorticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard’s reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples. Graphical abstract


Biochimie ◽  
2021 ◽  
Vol 185 ◽  
pp. 87-95
Author(s):  
Aleksandr S. Taraskin ◽  
Konstantin K. Semenov ◽  
Aleksandr V. Protasov ◽  
Alexey A. Lozhkov ◽  
Aleksandr A. Tyulin ◽  
...  

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