Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer.

There is a need to develop effective therapies for pancreatic ductal adenocarcinoma (PDA), a highly lethal malignancy with increasing incidence and poor prognosis. Although targeting tumour metabolism has been the focus of intense investigation for more than a decade, tumour metabolic plasticity and high risk of toxicity have limited this anticancer strategy. Here we use genetic and pharmacological approaches in human and mouse in vitro and in vivo models to show that PDA has a distinct dependence on de novo ornithine synthesis from glutamine.

Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1.

Pancreatic ductal adenocarcinoma (PDA) is a lethal, therapy-resistant cancer that thrives in a highly desmoplastic, nutrient-deprived microenvironment. Several studies investigated the effects of depriving PDA of either glucose or glutamine alone. However, the consequences on PDA growth and metabolism of limiting both preferred nutrients have remained largely unknown.

Ablation of insulin receptor substrates 1 and 2 suppresses -driven lung tumorigenesis.

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma (). Although KRAS direct binding to and activation of PI3K is required for -driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the context of mutant remains controversial. Here, we provide genetic evidence that lung-specific dual ablation of insulin receptor substrates 1/2 (/), which mediate insulin and IGF1 signaling, strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with activation and loss.

Bullying Victimization and Perpetration Among Adolescent Sport Teammates.

Purpose: Bullying is a specific pattern of repeated victimization explored with great frequency in school-based literature, but receiving little attention within sport. The current study explored the prevalence of bullying in sport, and examined whether bullying experiences were associated with perceptions about relationships with peers and coaches.

Method: Adolescent sport team members (n = 359, 64% female) with an average age of 14.

A proposed theoretical model to explain relative age effects in sport.

Exemplary scientific methods describe concepts and provide theories for further testing. For the field of relative age effects (RAEs) in sport, the scientific method appears to be limited to description. The purpose of this paper is to provide a theoretical model to explain RAEs in sport, which researchers can use to test the effects, as well as to generate new hypotheses and recommendations.