Three-Dimensional Characterization of the Vascular Bed in Bone Metastasis of the Rat by Microcomputed Tomography (MicroCT)

BackgroundAngiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography). They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities. Methodology/Principal Findings We have characterized the vasculature of bone metastases in 3D at different times of evolution of the disease. Metastases were induced in the femur of Wistar rats by a local injection of Walker 256/B cells. Microfil®, (a silicone-based polymer) was injected at euthanasia in the aorta 12, 19 and 26 days after injection of tumor cells. Undecalcified bones (containing the radio opaque vascular casts) were analyzed by microCT, and a first 3D model was reconstructed. Bones were then decalcified and reanalyzed by microCT; a second model (comprising only the vessels) was obtained and overimposed on the former, thus providing a clear visualization of vessel trajectories in the invaded metaphysic allowing quantitative evaluation of the vascular volume and vessel diameter. Histological analysis of the marrow was possible on the decalcified specimens. Walker 256/B cells induced a marked osteolysis with cortical perforations. The metaphysis of invaded bones became progressively hypervascular. New vessels replaced the major central medullar artery coming from the diaphyseal shaft. They sprouted from the periosteum and extended into the metastatic area. The newly formed vessels were irregular in diameter, tortuous with a disorganized architecture. A quantitative analysis of vascular volume indicated that neoangiogenesis increased with the development of the tumor with the appearance of vessels with a larger diameter. Conclusion This new method evidenced the tumor angiogenesis in 3D at different development times of the metastasis growth. Bone and the vascular bed can be identified by a double reconstruction and allowed a quantitative evaluation of angiogenesis upon time

Ribosomal S6 Kinase 2 (RSK2) Maintains Genomic Stability by Activating the Atm/p53-Dependent DNA Damage Pathway

10.1371/journal.pone.0074334PLoS ONE89-POLN

Employee Well-Being Under Corporate Psychopath Leaders

This chapter reports on twenty-one in-depth interviews in the UK and USA with corporateemployees who were currently working or had previously worked with a toxic leader in theform of a corporate psychopath. This is thus a chapter that is concerned with the impact onwell-being of working with a corporate psychopath. Corporate psychopathy was definedusing a measure of psychopathy involving proto-typical characteristics such as lying,cheating, egocentricity, emotional unresponsiveness and grandiosity. A contribution of thechapter is that it answers the call for research which links the destructive leadership literaturewith employee well-being. Research participants in both countries reported that their wellbeing was affected by psychopathic leadership, with reports of stress-related illnesses anddepression, including suicidal thoughts. The chapter concludes that corporate psychopaths, inboth the UK and USA, appear to have a similar protocol for achieving their objectives andachieve similar results. This protocol involves using loud, regular, public bullying combinedwith threats of violence to create a fearful, cowed and compliant workforce who can the moreeasily be manipulated and controlled by the abusive corporate psychopath. Researchparticipants in both the USA and UK suffered from severely reduced well-being because ofthis common experience