69 research outputs found
c-Met expression and activity in urogenital cancers – novel aspects of signal transduction and medical implications
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
The influence of tocolytic drugs on cardiac function, large arteries, and resistance vessels
Segment length mechanics of cardiac muscle; force, velocity and stiffness in cardiac muscle vary with length and calcium
Extensive eccentric contractions in intact cardiac trabeculae: revealing compelling differences in contractile behaviour compared to skeletal muscles
"Myocyte growth without physiological impairment in gradually induced rat cardiac hypertrophy".
Depression of contractility following stretches and releases applied during contraction to single frog atrial cardiac cells.
Isolated cat trabeculae in a simulated feline heart and arterial system. Contractile basis of cardiac pump function.
Ca2+ and segment length dependence of isometric force kinetics in intact ferret cardiac muscle.
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