ABSTRACT
Functionally, VEGF-based vessel formation is regulated by the NOTCH-1 pathway and expression of delta-like ligand 4 (Dll4) in tip cells. During the ‚nal stages of vessel formation, endothelial cells produce PDGF to recruit pericytes, leading to vessel stabilization. Tumor blood vessels tend to di‰er signi‚cantly from normal tissue blood vessels. Structurally, tumor vessels are tortuous, dilated, and leaky; lack pericyte
Contents 2.1 Tumor Vascular Inuence on Radiation Response 9 2.2 High-Dose Radiation E‰ects on Tumor Endothelial Cells 10 2.3 Ultrasound-Stimulated Microbubbles for Inducing Low-Dose Vascular E‰ects 13
2.3.1 Vascular E‰ects of Radiation 13 2.3.2 Microbubbles and Ultrasound 14 2.3.3 Microbubble-Based Enhancement of Radiation Cell Death E‰ects 15 2.3.4 Microbubble-Based Enhancement of Radiation Vascular E‰ects 15 2.3.5 Microbubble-Based Enhancement of Cell Death E‰ects 20 2.3.6 Asmase Pathway and Ceramide E‰ects on Treatments 20 2.3.7 Noninvasive Monitoring of Microbubble-Based Enhancement of Radiation E‰ects 22 2.3.8 Multiple Repeated Treatment E‰ects 24 2.3.9 Microbubble-Based Enhancement of Radiation E‰ects and Antiangiogenic Agents 24 2.3.10 Implications for Modern Delivery of Radiation erapy 26
References 26
coverage; and have abnormal basement membranes. Moreover, vascular density and vessel diameters are physiologically di‰erent in tumors compared to blood vessels in normal tissue. Such structural characteristics are associated with aberrations in local tumor blood ow and unusual uid dynamics (Goel et al., 2012). Other reported modes of tumor vascularization include “co-option” of neighboring persisting vessels, intussusceptions (splitting of existing vessels into two or more vessels), and recruitment of circulating endothelial progenitor cells from the bone marrow. Reports have also suggested that tumor cells themselves can act as blood vessels in a process called vascular mimicry (Mahadevan and Hart, 1990; Folkman, 1996; Folberg et al., 2000; Kerbel, 2000; Fukumura and Jain, 2007, 2008; Gordon et al., 2010; Fan et al., 2012; Tahergorabi and Khazaei, 2012).
