The dual role of mast cells in sporadic colorectal tumorigenesis: clinical and experimental evidence
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA528621 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8769640.fastq.gz | Fastqsanger.gz | |||
| SRR8769641.fastq.gz | Fastqsanger.gz | |||
| SRR8769642.fastq.gz | Fastqsanger.gz | |||
| SRR8769633.fastq.gz | Fastqsanger.gz | |||
| SRR8769643.fastq.gz | Fastqsanger.gz |
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Project description:Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders. Mouse bone marrow-derived mast cells were treated with IL3, IL3+IL33, or IL3+SCF. Six replicates each.
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Project description:Sporadic early onset colorectal carcinoma (EOCRC) is a growing problem that remains poorly understood. Clinical specificities and mechanisms of tumorigenesis might be relevant to both diagnosis and treatment. In this prospective study, clinicopathological features, genomic and gene expression profiles of sporadic EOCRC were compared to other well defined groups of CRC.
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Project description:The pathophysiologic mechanisms driving tumorigenesis and invasion of sporadic pituitary macroadenomas (PAs) remain unknown. We hypothesized that alterations in DNA methylation are associated with PA invasion and histopathology subtype, and that genome-scale methylation analysis may complement current classification methods for sporadic PAs.
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Project description:Mast cells are hematopoietic cells that reside preferentially in tissues exposed to internal and external environments. Mast cells sense immunological, inflammatory and environmental stimuli, and can be activated to release granules and generate inflammatory mediators. Mast cell-derived products confer protection against snake venoms and some parasite infections. Aberrant activation of mast cells is a major contributor to human pathology, including allergy, asthma and adverse drug reactions. Their strict tissue location has largely impeded the isolation of large numbers of primary mast cell for further analysis. To better understand the biology of mast cells, we analyzed the proteome of primary mouse mast cells by quantitative mass spectrometry
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