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Cystic Fibrosis (CF) is the most common monogenic disease among people of Western European descent and caused by mutations in the CFTR gene. However, the disease severity is immensely variable even among patients with similar CFTR mutations due to the possible effect of 'modifier genes'. To identify genetic modifiers, we applied RNA-seq based transcriptomic analyses in CF patients with a mild and severe lung phenotype. Global gene expression and enrichment analyses revealed that genes of the type I interferon response and ribosomal stalk proteins are potential modifiers of CF related lung dysfunction. The results provide a new set of CF modifier genes with possible implications as new therapeutic targets for the treatment of CF.

Cystic Fibrosis (CF) is the most common monogenic disease among people of Western European descent and caused by mutations in the CFTR gene. However, the disease severity is immensely variable even among patients with similar CFTR mutations due to the possible effect of ‘modifier genes’. To identify genetic modifiers, we applied RNA-seq based transcriptomic analyses in CF patients with a mild and severe lung phenotype. Global gene expression and enrichment analyses revealed that genes of the type I interferon response and ribosomal stalk proteins are potential modifiers of CF related lung dysfunction. The results provide a new set of CF modifier genes with possible implications as new therapeutic targets for the treatment of CF. [ABSTRACT FROM AUTHOR]

Background:Sorafenib has recently been shown to reduce tumour growth in hepatoblastoma (HB) xenografts. The effect of a combined administration with cytostatic agents was now investigated.Methods:Cell viability after treatment with sorafenib and different cytostatic agents was evaluated in two HB cell lines (HUH6 and HepT1) using MTT assay. ERK signalling was investigated by western blot, NOXA expression by rt-PCR, and formation of DNA adducts using immunocytology. NMRI mice bearing subcutaneous HUH6-derived tumours were treated with sorafenib alone or in combination with cisplatin. Tumour progression, viability, apoptosis, and vascularisation were monitored by tumour volume, AFP levels, TUNEL assay, and CD31 immunostaining, respectively.Results:The combination of sorafenib and cisplatin led to a remarkable decrease in cell viability. The cisplatin-induced enhanced ERK1/2 activation, but not NOXA expression and the formation of DNA adducts was partly abrogated by sorafenib. In HB xenografts, both, sorafenib and alternated application of sorafenib and cisplatin significantly reduced tumour growth (P<0.05). Levels of AFP were lower in both treated groups (P=0.08). Relative apoptotic areas were increased (P=0.003). Mean vascular density was the lowest in the sorafenib/CDDP group (P=0.02).Conclusion:The combination of sorafenib with cisplatin might be a promising treatment option for high risk or recurrent HB. [ABSTRACT FROM AUTHOR]

Background Multidrug resistance is a major reason for poor treatment results in advanced hepatoblastoma ( HB). Several alternative treatment options are currently under investigation to improve the prognosis of affected patients Aims This study aimed to analyse the impact of sorafenib on the viability of HB cells and xenotransplanted HB tumours. Methods Cell viability and apoptosis were evaluated in two HB cell lines ( HUH6 and HepT1) after treatment with sorafenib using MTT and Caspase 3 activation assay. Extracellular signal-regulated kinase ( ERK) phosphorylation was investigated using Western blot. In addition, sorafenib (30 mg/kg) was administered orally to NMRI mice bearing subcutaneous HUH6 derived tumours. Tumour progression and viability were monitored by tumour volume and α-fetoprotein ( AFP) levels, and apoptosis was assessed using TUNEL assay. Tumour angiogenesis and mean vascular density ( MVD) was determined using CD31 staining, ERK phosphorylation was detected using indirect immunofluorescence. Results Treatment with sorafenib led to decreased ERK phosphorylation, reduced cell viability and induction of apoptosis in HepT1 and HUH6 cells. In HB xenografts, sorafenib significantly reduced tumour growth compared with control ( P < 0.05). AFP levels were lower in the sorafenib group ( P = 0.07). Relative apoptotic areas detected using TUNEL assay were increased ( P = 0.003). CD31 staining revealed inhibition of angiogenesis, and mean vascular density was lower in the sorafenib group ( P = 0.02). ERK phosphorylation was reduced in tumours tissues after sorafenib treatment. Conclusion Treatment with sorafenib led to a potent inhibition of cell viability, tumour progression and angiogenesis. Sorafenib might therefore also be a promising treatment option for high risk or recurrent HB. [ABSTRACT FROM AUTHOR]

Describes several job titles from an Internet survey of media arts critics that are applied to individuals sharing the same role. Distinction between critics and reviewers; Impact of a critic on the audiences for whom they write; Objective of both the critic and the journalist.

A letter to the editor is presented in response to the article "In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency."