Tryptic bovine Fetuin digests O-glycopeptides hot ECD
Ontology highlight
ABSTRACT:
INSTRUMENT(S): 7600 ZenoTOF prototype
ORGANISM(S): Bovine Fetuin
SUBMITTER: 
Takashi Baba
PROVIDER: MSV000090137 | MassIVE | Mon Aug 15 13:45:00 BST 2022
REPOSITORIES: MassIVE
Similar Datasets
Project description:Advances in software and high resolution, high mass accuracy mass spectrometers have expanded their functionality beyond traditional data dependent acquisition (DDA) methods. Using a single platform, an orthogonal quadrupole time-of flight (QqTOF) mass spectrometer, the TripleTOF 5600, we have investigated the feasibility of implementing large-scale targeted quantitative assays, derived from discovery type data sets, using scheduled, high resolution multiple reaction monitoring (sMRM-HR) mass spectrometry. We assessed the selectivity and reproducibility of MRM-HR, also referred to as parallel reaction monitoring (PRM), measuring standard peptide concentration curves as well as system suitability assays. We specifically compared the robustness and accuracy of MRM-HR assays to traditional SRM workflows on triple quadrupole instruments. To determine the utility of sMRM-HR for large-scale targeted quantitative assays, we retention time scheduled over 500 peptides in a single LC-MS acquisition. High resolution and high mass accuracy of the full scan MS/MS spectra resulted in sufficient selectivity to monitor numerous MS/MS fragment ions per analyte precursor and provided flexibility for post-acquisition assay refinement and optimization. To demonstrate its applicability to biological samples, whole cell lysates from several E. coli wild-type and mutant strains were quantitatively assayed by sMRM-HR to confirm a previously generated candidate list of differentially expressed proteins. The ease of developing and implementing sMRM-HR assays derived directly from DDA discovery workflows on the same high resolution instrument platform facilitates downstream validation studies targeting many peptides for MS/MS level quantitation. This work provides a robust MRM-HR workflow for rapidly moving from discovery analysis to large-scale, multiplexed, targeted quantitation.
2015-03-10 | MSV000079077 | MassIVE
Project description:Data was acquired in TRAM (DDA+MRM), DDA-only, and MRM-only mode on a ZenoTOF 7600 with alkaline HILIC separation.
2024-05-08 | MSV000094712 | MassIVE
Project description: Not available
| S-EPMC3940724 | biostudies-literature
Project description:Acetaminophen (N-acetyl-p-aminophenol; APAP) is a mild analgesic and antipyretic used commonly worldwide. Although APAP is considered a safe and effective over-the-counter medication, it is also the leading cause of drug-induced acute liver failure. Its hepatotoxicity has been linked to the covalent binding of its reactive metabolite, N-acetyl p-benzoquinone imine (NAPQI), to proteins. The aim of this in vivo study was to identify APAP-protein targets in both rat and mouse liver, and to compare the results from both species, using bottom-up proteomics and targeted multiple reaction monitoring (MRM) experiments. Livers from rats and mice, treated with APAP, were homogenized and digested by trypsin. Digests were then fractionated by mixed-mode solid-phase extraction prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) using scheduled multiple reaction monitoring (MRM) acquisition. The targeted assays were optimized based on high-resolution MS/MS data from information-dependent acquisition (IDA) using control liver homogenates treated with a custom alkylating reagent forming a positional isomer of the APAP modification on all cysteine residues, in order to build an in-house modified peptide database for targeted analysis. A list of putative in vivo targets of APAP were screened from previous in vitro studies, data-dependent high-resolution MS/MS analyses of liver digests, as well as selected proteins from the target protein database (TPDB), an online resource which references previous reports of proteins found to be modified by acetaminophen. Multiple protein targets of APAP in each species were found, while confirming modification sites.
2022-02-17 | PXD027674 | Pride
Project description:Glioblastoma is the most common and malignant primary brain tumor in adults with current treatment presenting limited effectiveness. Resistance to therapy is consequence of the high molecular and cellular heterogeneity. Multitarget small molecules (MSMs) are emerging as a novel therapeutic strategy for the treatment of complex diseases, including cancer. In the present work, we have generated a novel family of indole-based MSMs designed to inhibit monoamine oxidases (MAOs), cholinesterases (ChEs) and histone deacetylases (HDACs), while acting as histamine H3 receptor (H3R) antagonists and sigma 1 receptor (S1R) agonists. For this, selected pharmacophoric moieties of the parent compounds Contilisant and Belinostat HDAC inhibitor were juxtaposed. 9 MSMs were synthesized and most of them exerted cytotoxic effect on glioma cells. Among them, 3 molecules were selected (MTP142, MTP156 and MTP150), and additional experiments revealed that they inhibited glioma stem cell (GSCs) activity, did not present toxicity and are expected to cross the BBB. In vivo and Omic studies were performed with MTP150 molecule and results showed that it significantly reduced tumor growth in vivo, both alone and in combination with temozolomide (TMZ). Finally, transcriptomic and proteomic analyses on patient-derived GSCs revealed a deregulation in cell cycle and neurotransmission activity by the treatment with MTP150. In conclusion, our data reveal the efficacy of a novel family of MSMs in the pre-clinical setting of glioblastoma.
2026-06-01 | GSE283024 | GEO
Project description: Not available
| S-EPMC2773718 | biostudies-literature
Project description:Apoptotic cells are immunosuppressive, creating a potential therapeutic barrier in cancer therapy. In this reportwe investigated responses to apoptotic tumor cell phagocytosis (i.e. efferocytosis) after therapy in the tumor draining lymph node (TDLN). Treatment with cisplatin or the BRAF inhibitor PLX4720 caused a significant increase in accumulation of apoptotic tumor material in the TDLN. We identified the primary phagocyte population responsible for clearing dying tumors in the TDLN was medullary sinus macrophages (MSMs). Tumor cell efferocytosis by MSMs induced an immune suppressive transcriptional program distinct from other macrophage or dendritic cell populations in the TDLN. One of the most differentially induced mRNAs in MSMs wasIl33,coding fora potent immune-regulatory cytokine. Administration of neutralizing anti-IL-33 receptor antibodies or deletion ofIl33in MSMs altered tumor responses to therapy with a significant enhancement of anti-tumor activity compared to controls. Mechanistically, IL-33 activated Treg cells in the TDLN with subsequent suppression of CD8+T cell responses. Importantly, combining IL-33 receptor blockade, BRAF inhibitor, and PD-1 blockade significantly improved tumor regression with enhanced, CD8+T cell dependent immunity. Finally, apoptotic tumor cells induced IL-33 expression in human macrophages, IL-33 expression in sentinel lymph nodes positively corresponded with disease stage and negatively correlated with survival in melanoma and breast cancer. Thus, the data identifies an immune response to therapy that abrogates nascent anti-tumor immunity, providing a previously undescribed functional interaction with broad implications for cancer therapy.
2025-01-28 | GSE268778 | GEO
Project description:Apoptotic cells are immunosuppressive, creating a potential therapeutic barrier in cancer therapy. In this reportwe investigated responses to apoptotic tumor cell phagocytosis (i.e. efferocytosis) after therapy in the tumor draining lymph node (TDLN). Treatment with cisplatin or the BRAF inhibitor PLX4720 caused a significant increase in accumulation of apoptotic tumor material in the TDLN. We identified the primary phagocyte population responsible for clearing dying tumors in the TDLN was medullary sinus macrophages (MSMs). Tumor cell efferocytosis by MSMs induced an immune suppressive transcriptional program distinct from other macrophage or dendritic cell populations in the TDLN. One of the most differentially induced mRNAs in MSMs wasIl33,coding fora potent immune-regulatory cytokine. Administration of neutralizing anti-IL-33 receptor antibodies or deletion ofIl33in MSMs altered tumor responses to therapy with a significant enhancement of anti-tumor activity compared to controls. Mechanistically, IL-33 activated Treg cells in the TDLN with subsequent suppression of CD8+T cell responses. Importantly, combining IL-33 receptor blockade, BRAF inhibitor, and PD-1 blockade significantly improved tumor regression with enhanced, CD8+T cell dependent immunity. Finally, apoptotic tumor cells induced IL-33 expression in human macrophages, IL-33 expression in sentinel lymph nodes positively corresponded with disease stage and negatively correlated with survival in melanoma and breast cancer. Thus, the data identifies an immune response to therapy that abrogates nascent anti-tumor immunity, providing a previously undescribed functional interaction with broad implications for cancer therapy.
2025-01-28 | GSE268774 | GEO
Project description:Ongoing immunomodulatory strategies in tumors characterized by an overall hot immune phenotype may improve prognosis of patients with non-small cell lung cancer (NSCLC). Our objective was to develop a reliable and stable scoring system for the identification of immunologically hot NSCLC and to evaluate its association with response to immunotherapies. A Hot Oral Tumor (HOT) score was developed using data from The Cancer Genome Atlas. HOT score was computed in 82 patients with NSCLC treated with second-line immunotherapy targeting PD-1/PD-L1. High HOT score was associated with a statistically significant improved clinical outcome.
2022-07-07 | GSE161537 | GEO
Project description:Ongoing immunomodulatory strategies in tumors characterized by an overall hot immune phenotype may improve prognosis of head and neck squamous cell carcinomas (HNSCC). Our objective was to develop a reliable and stable scoring system for the identification of immunologically hot HNSCC and to evaluate its association with response to immunotherapies. A Hot Oral Tumor (HOT) score was developed using data from The Cancer Genome Atlas. HOT score was computed in 102 patients with HNSCC treated with immunotherapy targeting PD-1/PD-L1 in the context of clinical trials. High HOT score was associated with a statistically significant improved clinical outcome.
2022-07-07 | GSE159067 | GEO