WCPFC-SC5-2005/SA-IP-05

Factors influencing the size of albacore tuna sampled from the South Pacific albacore longline fisherie

Minimal benefit of tonsillectomy in T1-T2 tonsillar squamous cell carcinoma treated with chemoradiotherapy

Background: Chemoradiotherapy (CRT) has become the mainstay of treatment for tonsillar squamous cell carcinoma (SCC). Pre-CRT tonsillectomy is frequently performed, mostly for small primary tumors (T1-T2). However, the benefits of pre-CRT tonsillectomy remain unclear. Methods: A retrospective review was performed in 66 patients with T1-T2 tonsillar SCCs treated by CRT from 1997 to 2009. The efficacy of pre-CRT tonsillectomy was analyzed with regard to oncological and functional outcomes. Results: Thirty patients (45.5%) received tonsillectomy (pre-CRT tonsillectomy group), and 36 patients (54.5%) did not (CRT group). Except for a trend toward more T1 cases (33.3% vs. 13.9%, p = 0.061) and significantly less chemotherapy use (60% vs. 86.1%, p = 0.016) in the pre-CRT tonsillectomy group, there were no differences between the two groups in terms of age, gender, N classification (nodal status), overall stage, radiation dose, duration, or technique. In the pre-CRT tonsillectomy group, eight cases (26.7%) achieved an adequate operative margin judged by the surgeon, and only one (12.5%) had a negative pathological margin. In long-term follow-up, there were no statistically significant differences between the two groups regarding local (93.3% vs. 91.7%, p = 0.82) or regional control (93.3% vs. 94.4%, p = 0.84). The pre-CRT tonsillectomy group did not have a better 5-year disease-specific survival rate (83.3% vs. 94.4%, p = 0.177) or 5-year overall survival rate (70% vs. 94.4%, p = 0.017). There were no differences in complications or functional results (feeding tube and tracheostomy dependence), and quality of life demonstrated no significant difference. Conclusion: Pre-CRT tonsillectomy contributes little to oncological and functional outcomes in patients with T1-T2 tonsillar SCC

Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia

Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer1, 2, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer3, 4, 5. Additionally, although many people with cachexia show hypermetabolism3, 6, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell–based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid–induced oxidative stress could be targeted to prevent cancer-induced cachexia.ASTAR (Agency for Sci., Tech. and Research, S’pore)NMRC (Natl Medical Research Council, S’pore

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries