2018
DOI: 10.1186/s12014-018-9189-x
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Proteomics-based insights into mitogen-activated protein kinase inhibitor resistance of cerebral melanoma metastases

Abstract: BackgroundMAP kinase inhibitor (MAPKi) therapy for BRAF mutated melanoma is characterized by high response rates but development of drug resistance within a median progression-free survival (PFS) of 9–12 months. Understanding mechanisms of resistance and identifying effective therapeutic alternatives is one of the most important scientific challenges in melanoma. Using proteomics, we want to specifically gain insight into the pathophysiological process of cerebral metastases.MethodsCerebral metastases from mel… Show more

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Cited by 17 publications
(15 citation statements)
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“…Protein concentrations were premeasured using a Bradford assay. For each sample 20 µg protein was used for the in-solution digest performed according to a variation 21 of the FASP protocol 22 . Dried samples were reconstituted as previously described 23 , 24 in 5 µl 30% formic acid (FA) containing 4 synthetic standard peptides and diluted with 40 µl mobile phase A (97.9% H 2 O, 2% ACN, 0.1% FA).…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…Protein concentrations were premeasured using a Bradford assay. For each sample 20 µg protein was used for the in-solution digest performed according to a variation 21 of the FASP protocol 22 . Dried samples were reconstituted as previously described 23 , 24 in 5 µl 30% formic acid (FA) containing 4 synthetic standard peptides and diluted with 40 µl mobile phase A (97.9% H 2 O, 2% ACN, 0.1% FA).…”
Section: Methodsmentioning
confidence: 99%
“…Analysis and interpretation of LC–MS data was performed essentially as described 21 using the open source software MaxQuant (version 1.6.3.4) 25 , 26 including the Andromeda search engine and the Perseus statistical analysis package 25 , 26 . Protein inference was achieved aligning against homo sapiens in the SwissProt Database setting the parameters (mass tolerance, missed cleavages, fixed/variable modifications, minimum of peptide identifications) as defined 21 . Label-free quantification (LFQ) revealed values for each individual protein, which were conducted for quantitative assessment of protein regulation using the Perseus statistical analysis package 27 .…”
Section: Methodsmentioning
confidence: 99%
“…Based on published proteomics data, levels of NETs proteins and S100A8/CRP ratios were compared in different patient cohorts. (A,B) Melanoma study by Zila et al [49]. Differences in protein abundances as well as in S100/CRP ratios in cerebral metastases samples of good versus poor melanoma patient responders to MAPKi treatment are shown.…”
Section: Nets Proteins and S100a8/crp Ratio May Serve As Prognostic Bmentioning
confidence: 96%
“…To collect additional evidence for neutrophil activation in another kind of tumor and its potential association with overall survival, we re-evaluated published proteomics data from our laboratory generated from the analysis of cerebral melanoma metastases [49]. Melanoma patients (n = 18) undergoing a MAPKi therapy were classified depending on progression-free survival (PFS) in good (PFS ≥ 6 months) and poor responders (PFS ≤ 3 months).…”
Section: Nets Proteins and S100a8/crp Ratio May Serve As Prognostic Bmentioning
confidence: 99%
“…To collect additional evidence for neutrophil activation in another kind of tumor and its potential association with overall survival, we re-evaluated published proteomics data from our laboratory generated from the analysis of cerebral melanoma metastases [47].…”
Section: Nets Proteins and S100a8/crp Ratio May Serve As Prognostic Bmentioning
confidence: 99%