DWI during CRT for HNC allows more accurate response prediction than anatomical imaging, correlating significantly with 2-year LRC.

• Whole-body MRI with diffusion weighting (WB-DWI/MRI) helps to assess the operability of suspected ovarian cancer. • Interobserver agreement is good for primary tumour characterisation, peritoneal and distant staging. • WB-DWI/MRI improves mesenteric/serosal metastatic spread assessment compared with CT and FDG-PET/CT. • Retroperitoneal/cervical-thoracic nodal staging using qualitative DWI criteria was reasonably accurate. • WB-DWI/MRI and FDG-PET/CT showed the highest diagnostic impact for detecting thoracic metastases.

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DFNA5 was first identified as a gene causing autosomal dominant hearing loss (HL). Different mutations have been found, all exerting a highly specific gain-of-function effect, in which skipping of exon 8 causes the HL. Later reports revealed the involvement of the gene in different types of cancer. Epigenetic silencing of DFNA5 in a large percentage of gastric, colorectal and breast tumors and p53-dependent transcriptional activity have been reported, concluding that DFNA5 acts as a tumor suppressor gene in different frequent types of cancer. Despite these data, the molecular function of DFNA5 has not been investigated properly. Previous transfection studies with mutant DFNA5 in yeast and in mammalian cells showed a toxic effect of the mutant protein, which was not seen after transfection of the wild-type protein. Here, we demonstrate that DFNA5 is composed of two domains, separated by a hinge region. The first region induces apoptosis when transfected in HEK293T cells, the second region masks and probably regulates this apoptosis inducing capability. Moreover, the involvement of DFNA5 in apoptosis-related pathways in a physiological setting was demonstrated through gene expression microarray analysis using Dfna5 knockout mice. In view of its important role in carcinogenesis, this finding is expected to lead to new insights on the role of apoptosis in many types of cancer. In addition, it provides a new line of evidence supporting an important role for apoptosis in monogenic and complex forms of HL. Keywords: tumor suppressor; hearing loss; apoptosis; dfna5; cancer; GSEA INTRODUCTION DFNA5 first was discovered in a Dutch family with autosomal dominant hearing loss (HL). 1 Not much was known concerning its cellular function and how its function was related to HL. Recently, a novel mutation in DFNA5 has been identified in a Korean family, totaling five families with DFNA5 HL. 2 These families all have different genomic DFNA5 mutations, but in each case the DFNA5 mRNA transcript skips exon 8, resulting in a frameshift and a premature truncation of the protein. [1][2][3][4][5] These findings have led to the hypothesis that DFNA5-associated HL is attributable to a highly specific gain-of-function mutation, in which skipping of one exon causes disease while mutations in other parts of this gene may not result in HL at all. Further experimental evidence for this hypothesis was provided by the finding that transfection of mutant DFNA5 causes cell death in both yeast 6 and mammalian 7 cells and by the discovery of a new DFNA5 mutation. 8 The latter mutation truncated the protein in the fifth exon, but did not segregate with HL and was present in family members with normal hearing. The hypothesis was further corroborated by a mouse that lacked the Dfna5 protein. This knockout (KO) mouse did not display any HL and, as a consequence, was not a suitable animal model to study DFNA5-associated HL. 9 To date, little information is available on the physiological function of DFNA5. However, since its identification, the small num...

The purpose of this study was to evaluate the accuracy of diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating HCC from benign cirrhotic lesions compared with conventional dynamic contrast-enhanced MRI. Fifty-five patients with cirrhosis underwent conventional and DW-MRI at 1.5 Tesla. Signal intensity ratios (SI(ratio)) of solid liver lesions to adjacent hepatic parenchyma were measured for b0, b100, b600 and b1000, and the apparent diffusion coefficients (ADC) were calculated. In 27 patients, imaging results were compared to histopathology, and in 28 patients, to imaging follow-up. Based on predetermined thresholds, sensitivity and specificity of DW-MRI and conventional MRI were compared. SI(ratio) was significantly different between malignant and benign lesions at all b-values (P < 0.0001). No significant difference in ADC was seen (P = 0.47). For detection of malignant lesions, DW-MRI with b600-SI(ratio) yielded a sensitivity of 95.2% compared to 80.6% for conventional MRI (P = 0.023) and a specificity of 82.7% compared to 65.4% (P = 0.064). The improved accuracy was most beneficial for differentiating malignant lesions smaller than 2 cm. DW-MRI with b600-SI(ratio) improved the detection of small HCC and the differentiation of pseudotumoral lesions compared with conventional MRI.