Chewing the Fat on Tumor Cell Metabolism

Tumor cells undergo a metabolic shift toward specific bioenergetic (glycolysis) and anabolic (protein and lipid synthesis) processes that promote rapid growth. Nomura et al. (2010) now demonstrate that an increase in monoacylglycerol lipase (MAGL) drives tumorigenesis through the lipolytic release and remodeling of free fatty acids

East Asian audio-visual collaboration and the global expansion of Chinese media

This article investigates the significant re-orientation of audio-visual production in East Asia over the last few years brought about by the rise of China, beginning with the proposition that unprecedented change is occurring in East Asian media production. While the 'Sinophone world' has been the locus of critical analysis in the past, all eyes are now focused on China. Flows of knowledge, expertise and content are becoming significant in this mediascape, yet this dimension has been overlooked by most scholarship in the field. Conceptual and theoretical frameworks based on cross-border consumption of East Asian content require urgent revision. This article shows how media collaborations are changing global media practice and East Asian media flows through a variety of contemporary international collaborations, as well as relevant policy frameworks that impact, positively or negatively, productions by international partners working in film, television and online and mobile video content

Improved prediction of postoperative paediatric cerebellar mutism syndrome using an artificial neural network

BACKGROUND: Postoperative paediatric cerebellar mutism syndrome (pCMS) is a common but severe complication which may arise following the resection of posterior fossa tumours in children. Two previous studies have aimed to preoperatively predict pCMS, with varying results. In this work, we examine the generalisation of these models and determine if pCMS can be predicted more accurately using an artificial neural network (ANN). METHODS: An overview of reviews was performed to identify risk factors for pCMS, and a retrospective dataset collected as per these defined risk factors from children undergoing resection of primary posterior fossa tumours. The ANN was trained on this dataset and its performance evaluated in comparison to logistic regression and other predictive indices via analysis of receiver operator characteristic curves. Area under the curve (AUC) and accuracy were calculated and compared using a Wilcoxon signed rank test, with p<0.05 considered statistically significant. RESULTS: 204 children were included, of whom 80 developed pCMS. The performance of the ANN (AUC 0.949; accuracy 90.9%) exceeded that of logistic regression (p<0.05) and both external models (p<0.001). CONCLUSION: Using an ANN, we show improved prediction of pCMS in comparison to previous models and conventional methods

Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1

Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis. This is achieved through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor (HIF1α) and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of these transcription factors is mediated by S6K1. Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease

Shopping, sex, and lies: Mimong/Sweet Dreams (1936) and the disruptive process of colonial girlhood

In the early Korean film we follow the melodramatic life of an unfaithful housewife. Sweet Dreams situates itself at the heart of the Korean colonial experience with urban Seoul as the backdrop to a narrative of deceit, adultery and consumerism. This article will explore how Sweet Dreams functions both as a warning about the perils of modern womanhood and, simultaneous to this, a vision of consumerist pleasure and delight. This article examines how the actions of lead character Ae-soon constitute a process by which the adult women is rendered girl via her positioning at the locus of female visual pleasure. I use the term girl as a process rather than a static category since, as will be explored, the attributes of girlhood with relation to Sweet Dreams are both expansive and fluid. In this way girlhood can be appropriated for transgressive purposes, not only in terms of a visualization of a desiring femininity, but also as a marker of colonial dissent. I argue that Sweet Dreams uses the interplay between the categories of woman and girl to disrupt the colonial drive towards a productive body in favour of the delights of consumption

Synergistic Anticancer Effects of the 9.2.27PE Immunotoxin and ABT-737 in Melanoma

In cancer, combinations of drugs targeting different cellular functions is well accepted to improve tumor control. We studied the effects of a Pseudomonas exotoxin A (PE) - based immunotoxin, the 9.2.27PE, and the BH-3 mimetic compound ABT-737 in a panel of melanoma cell lines. The drug combination resulted in synergistic cytotoxicity, and the cell death observed was associated with apoptosis, as activation of caspase-3, inactivation of Poly (ADP-ribose) polymerase (PARP) and increased DNA fragmentation could be prevented by pre-treatment with caspase and cathepsin inhibitors. We further show that ABT-737 caused endoplasmic reticulum (ER) stress with increased GRP78 and phosphorylated eIF2α protein levels. Moreover, treatment with ABT-737 increased the intracellular calcium levels, an effect which was enhanced by 9.2.27PE, which as a single entity drug had minimal effect on calcium release from the ER. In addition, silencing of Mcl-1 by short hairpin RNA (shRNA) enhanced the intracellular calcium levels and cytotoxicity caused by ABT-737. Notably, the combination of 9.2.27PE and ABT-737 caused growth delay in a human melanoma xenograft mice model, supporting further investigations of this particular drug combination