Primary Cardiac Tumors in Infancy: A Case Report and Literature Review.

Sudden death in infants due to primary cardiac tumors is extremely rare. Herein we describe a case of an 8-month-old male infant, without any previous medical history, who died in a hospital in the city of Medellín-Antioquia, Colombia. The family stated that approximately 15 minutes after he received a bottle, the baby became cyanotic and subsequently lost consciousness. He was taken to the hospital immediately; however, he arrived lifeless. As this was a sudden death case, the child was referred to the Institute of Legal Medicine and Forensic Sciences in the city of Medellín to clarify the cause, manner, and mechanism of death. The forensic autopsy revealed a eutrophic infant with central and peripheral cyanosis, without signs of trauma, and the internal examination found a single cardiac tumor in the anterior wall of the left ventricle. The mass was white and whorled; histological evaluation diagnosed a fibroma. The manner of death was natural due to a cardiogenic shock caused by a primary tumor.

ß-catenin links von Hippel-Lindau to aurora kinase A and loss of primary cilia in renal cell carcinoma.

von Hippel-Lindau (VHL) gene mutations are associated with clear cell renal cell carcinoma (ccRCC). A hallmark of ccRCC is loss of the primary cilium. Loss of this key organelle in ccRCC is caused by loss of VHL and associated with increased Aurora kinase A (AURKA) and histone deacetylase 6 (HDAC6) activities, which drive disassembly of the primary cilium. However, the underlying mechanism by which VHL loss increases AURKA levels has not been clearly elucidated, although it has been suggested that hypoxia-inducible factor-1α (HIF-1α) mediates increased AURKA expression in VHL-null cells. By contrast, we found that elevated AURKA expression is not increased by HIF-1α, suggesting an alternate mechanism for AURKA dysregulation in VHL-null cells. We report here that AURKA expression is driven by ß-catenin transcription in VHL-null cells. In a panel of RCC cell lines, we observed nuclear accumulation of ß-catenin and increased AURKA signaling to HDAC6. Moreover, HIF-1α inhibited AURKA expression by inhibiting ß-catenin transcription. VHL knockdown activated ß-catenin and elevated AURKA expression, decreased primary cilia formation, and caused significant shortening of cilia length in cells that did form cilia. The ß-catenin responsive transcription inhibitor iCRT14 reduced AURKA levels and rescued ciliary defects, inducing a significant increase in primary cilia formation in VHL-deficient cells. These data define a role for ß-catenin in regulating AURKA and formation of primary cilia in the setting of VHL deficiency, opening new avenues for treatment with ß-catenin inhibitors to rescue ciliogenesis in ccRCC.

Characteristics of schools in which fatal shootings occur.

School-based violence, and fatal school shootings in particular, have gained increased attention in the media and psychological literature. Most reports have focused on the characteristics of perpetrators, but there is a growing awareness that school-related factors may also influence the occurrence of fatal school shootings. The current study examined several key characteristics of all schools where random (38) and targeted (96) fatal shootings occurred in the United States between 1966 and 2009. These were compared with a group (138) of schools randomly selected to represent the population of all schools in the United States. The size of a school's enrollment, urban or suburban locale, public funding, and predominantly non-white enrollment were positively associated with fatal shootings. Universities and colleges were disproportionately associated with random shootings and high schools with targeted ones. It was proposed that characteristics of schools that allow feelings of anonymity or alienation among students may help create environmental conditions associated with fatal school shootings. Implications for future research and interventions are considered.

Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells.

The role of the RhoA/Rho kinase (ROCK) signaling pathway in cell survival remains a very controversial issue, with its activation being pro-apoptotic in many cell types and anti-apoptotic in others. To test if ROCK inhibition contributes to tumor cell survival or death following chemotherapy, we treated cisplatin damaged neuroblastoma cells with a pharmacological ROCK inhibitor (Y27632) or sham, and monitored cell survival, accumulation of a chemoresistant phenotype, and in vivo tumor formation. Additionally, we assayed if ROCK inhibition altered the expression of genes known to be involved in cisplatin resistance. Our studies indicate that ROCK inhibition results in increased cell survival, acquired chemoresistance, and enhanced tumor survival following cisplatin cytotoxicity, due in part to altered expression of cisplatin resistance genes. These findings suggest that ROCK inhibition in combination with cisplatin chemotherapy may lead to enhanced tumor chemoresistance in neuroblastoma.