Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma
British Journal of Cancer advance online publication, May 11 2017. doi:10.1038/bjc.2017.126
Authors: Zhen Dong, Qian Lei, Rui Yang, Shunqin Zhu, Xiao-Xue Ke, Liqun Yang, Hongjuan Cui & Liang Yi
Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using electronic primary care records
British Journal of Cancer advance online publication, May 11 2017. doi:10.1038/bjc.2017.127
Authors: Luke T A Mounce, Sarah Price, Jose M Valderas & William Hamilton
Mutation status among patients with sinonasal mucosal melanoma and its impact on survival
British Journal of Cancer advance online publication, May 11 2017. doi:10.1038/bjc.2017.125
Authors: Moran Amit, Samantha Tam, Ahmed S Abdelmeguid, Dianna B Roberts, Yoko Takahashi, Shaan M Raza, Shirley Y Su, Michael E Kupferman, Franco DeMonte & Ehab Y Hanna
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. It is characterized by highly complex karyotypes with structural and numerical chromosomal alterations. The observed OS-specific characteristics in localization and frequencies of chromosomal breakages strongly implicate a specific set of responsible driver genes or a specific mechanism of fragility induction. In this study, a comprehensive assessment of somatic copy number alterations (SCNAs) was performed in 160 OS samples using whole-genome CytoScan High Density arrays (Affymetrix, Santa Clara, CA). Genes or regions frequently targeted by SCNAs were identified. Breakage analysis revealed OS specific unstable regions in which well-known OS tumor suppressor genes, including TP53, RB1, WWOX, DLG2, and LSAMP are located. Certain genomic features, such as transposable elements and non-B DNA-forming motifs were found to be significantly enriched in the vicinity of chromosomal breakage sites. A complex breakage pattern – chromothripsis – has been suggested as a widespread phenomenon in OS. It was further demonstrated that hyperploidy and in particular chromothripsis were strongly correlated with OS patient clinical outcome. The revealed OS-specific fragility pattern provides novel clues for understanding the biology of osteosarcoma. This article is protected by copyright. All rights reserved.
Survival in exsanguinating cardiac arrest patients is poor, as is neurological outcome in survivors. Hypothermia has traditionally been seen as harmful to trauma patients and associated with increased mortality; however, there has been speculation that cooling to very low temperatures (≤20°C) could be used to treat haemorrhagic trauma patients by the induction of a suspended animation period through extreme cooling, which improves survival and preserves neurological function. This has been termed emergency preservation and resuscitation (EPR).
MethodsA systematic review of the literature was used to examine the evidence base behind the use of deep and profound hypothermia in haemorrhagic shock (HS). It included original research articles (human or animal) with cooling to ≤20°C after HS or an experimental model replicating it. Normovolaemic cardiac arrest, central nervous system injury and non-HS models were excluded.
ResultsTwenty articles using 456 animal subjects were included, in which 327 were cooled to ≤20°C. All studies describing good survival rates were possible using EPR and 19/20 demonstrated that EPR can preserve neurological function after prolonged periods of circulatory arrest or minimal circulatory flow. This additional period can be used for surgical intervention to arrest haemorrhage in HS that would otherwise be lethal.
ConclusionsThe outcomes of this review have significant implications for application to human patients and the ongoing human clinical trial (EPR for Cardiac Arrest from Trauma). Current evidence suggests that hypothermia ≤20°C used in the form of EPR could be beneficial to the HS patient.
