Osteosarcoma is the most common primary malignant tumour of bone. Currently, despite treatment with multi-agent chemotherapy and limb salvage surgery, the five-year survival rate for osteosarcoma remains at 70%. The pathogenesis of osteosarcoma is complex and involves alterations in cellular apoptosis, adhesion, migration, invasion and molecular signalling. Research most recently has focused on the molecular basis of the disease with the goal of identifying novel therapeutic targets. To this end, mesenchymal stem cells (MSCs) have been identified to play a role in sarcomagenesis. MSC transformation may give rise to tumours, whereas interactions of MSCs with osteosarcoma cells in the tumour microenvironment may cause increased cell proliferation. This is in stark contrast to the role of MSCs as a promising source for tissue repair and regeneration. In order to utilize MSCs for biological reconstruction in the setting of osteosarcoma, further research is necessary to delineate the role of MSCs in osteosarcoma transformation and progression.
Part of the book: Osteosarcoma
Polymorphonuclear (neutrophil) granulocytes (PMNs) are an essential part of the innate immune responses and key instigators and effectors of the underlying pathological mechanisms (endothelial damage, interstitial histolysis, cytokine production, phagocytosis) leading to post-injury inflammation and secondary tissue injury. In 2004, the formation of neutrophil extracellular traps (NETs) was identified as an additional defence mechanism of PMN against microbes. The understanding of complex regulation of neutrophil functions and NET formation is essential for differentiating between healthy and pathological inflammatory response, which frequently determines if patient recovers uneventfully or develops catastrophic complications. Recent discoveries have revealed the potential role of NETs in the pathogenesis of a wide range of non-infectious diseases, including post-injury sterile inflammation. In such conditions, both spontaneous NET formation and impaired NETosis are documented. In this chapter, we review the evidence for the role of NETs in post-injury inflammation, the key molecular and cellular participants in pathological NET formation, the clinical relevance of NETs in post-injury complications and the therapeutic potential of NET inhibition/clearance.
Part of the book: Role of Neutrophils in Disease Pathogenesis
Introduction: Almost 50 years ago, computed tomography (CT) revolutionized the management of traumatic brain injury (TBI) by imagining intracranial hematomas. This allowed prompt and accurate selection of patients who would benefit from surgical evacuation. Since then, unenhanced CT has been the gold standard imaging modality for patients with acute TBI. Today, multidetector CT can track intravenous contrasts flowing through brain creating maps that depict the speed and the amount of blood at capillary level. This imaging modality takes the name of perfusion CT. Perfusion CT is routinely used during the hyperacute phase of patients suffering from stroke to diagnose areas of penumbra (poorly perfused but still viable brain tissue) that may benefit from revascularization. Here, we summarize the current status of the research on the role of perfusion CT in patients suffering from TBI.
Part of the book: Traumatic Brain Injury