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- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 5. |
- Shaw, DE, et al.
(författare)
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Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort
- 2015
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 46:5, s. 1308-1321
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Tidskriftsartikel (refereegranskat)abstract
- U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach.
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- Hosen, Ismail, et al.
(författare)
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Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:7, s. 1621-1629
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the promoter of the telomerase reverse transcriptase (TERT) and fibroblast growth factor receptor 3 (FGFR3) genes constitute the most recurrent somatic alterations in urothelial carcinoma of bladder. In this study, we screened DNA from 327 urothelial bladder carcinomas from well-documented patients, with different stages and grades and known TERT promoter mutational status, for FGFR3 alterations and measured relative telomere length (RTL). Although, the frequency of the TERT promoter mutations was higher than those in FGFR3; however, the alterations at the two loci occurred together more frequently than per chance [Odds ratio (OR)=4.93, 95% CI=2.72-8.92, p<0.0001]. While tumors with TERT promoter and FGFR3 mutations had shorter RTL than those without mutations (p<0.0001), the TERT promoter mutations in conjunction with the common allele of the rs2853669 polymorphism defined sub-group of patients with an observed decreased overall survival (OR=2.15, 95% CI=1.00-4.61) and increased recurrence in patients with TaG1+TaG2 disease categories (OR=3.68, 95%CI=1.12-12.05). The finding of shorter telomeres in tumors with TERT promoter and/or FGFR3 mutations than without mutations implies mechanistic relevance of telomere biology in cancer progression. The observed association with recurrence and survival shows that the TERT promoter mutations can potentially be used as markers to refine selection of patients for different treatments. The overwhelming frequency of the TERT promoter mutations also represents a case for development of an eventual therapeutic target. What's New? The identification of recurrent somatic mutations in bladder cancer opens the door to the development of new prognostic and therapeutic tools. Here, the TERT promoter mutations in conjunction with a common variant, rs2853669, define a subset of patients with increased risk of recurrence and poor survival. Mutations in FGFR3, in contrast, were not independently associated with either disease recurrence or overall survival. Tumors with mutations in FGFR3 or the TERT promoter carried shorter telomeres than those without mutations. The findings highlight the prognostic potential of TERT mutations and reveal a possible etiological role for telomere biology in bladder cancer.
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