Antibiotics in Cystic Fibrosis Sputum
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Sputum
DISEASE(S): Cystic Fibrosis
PROVIDER: ST001365 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
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| mwtab | Other |
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Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
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Project description:Cystic Fibrosis is a life limiting disease due to mutations in the Cystic Fibrosis Conductance Gene Regulator (CFTR). This is associated with a multiorgan disease combining pancreatic insufficiency, chronic infected bronchopathy and production of a salty sweat. Increased survival of patients leads to observation of new complications, including proximal tubule transport dysfunctions with increased output of glucose, amino acids, phosphate, calcium, uric acid, and low Molecular Weight proteins, which ultimately triggers tubulo-interstitial injury and chronic kidney disease. (Jouret et al. 2007) Exosomes are membrane vesicles stemming from Multi-Vesicular Bodies. They reflect the biological state of the cell they stem from because they incorporate various bioactive molecules from their cell of origin, which can be transferred to target cells. They are therefore ideal biomarkers for early diagnosis, prediction of disease progression or response to treatment. Urinary exosomes have been largely investigated in kidney or urothelial diseases and exosomal proteins proved to be biomarkers reflecting renal cellular biology. We hypothetized that urinary exosomal proteins might be differentially expressed, according to the presence of the mutation in the CFTR gene and its correction. We analyzed urinary exosomes of patients with CF and healthy controls based on their protein content determined by high resolution mass spectrometry, in combination with Gene Set Enrichment Analysis. These results were compared to those obtained in exosomes collected in patients treated with CFTR modulators.
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Project description:Mutations of the CFTR gene cause cystic fibrosis (CF), the most common recessive monogenic disease worldwide. These mutations alter the synthesis, processing, function, or half-life of CFTR, the main chloride channel expressed in the apical membrane of epithelial cells in the airway, intestine, pancreas, and reproductive tract. Lung disease is the most critical manifestation of CF. It is characterized by airway obstruction, infection, and inflammation that lead to fatal tissue destruction. In spite of great advances in early and multidisciplinary medical care, and in our understanding of the pathophysiology, CF is still considerably reducing the life expectancy of patients. This review highlights the current development in pharmacological modulators of CFTR, which aim at rescuing the expression and/or function of mutated CFTR. While only Kalydeco® and Orkambi® are currently available to patients, many other families of CFTR modulators are undergoing preclinical and clinical investigations. Drug repositioning and personalized medicine are particularly detailed in this review as they represent the most promising strategies for restoring CFTR function in CF.
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