a quantitative theory of solid tumor growth, metabolic rate and vascularization的定量理论固体肿瘤生长,代谢率和血管化.pdfVIP

A Quantitative Theory of Solid Tumor Growth, Metabolic Rate and Vascularization Alexander B. Herman1,3,4*, Van M. Savage2,3,4, Geoffrey B. West3,4 1 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States of America, 2 Department of Biomathematics, School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 3 Santa Fe Institute, Santa Fe, New Mexico, United States of America, 4 Theoretical Division, T-8, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America Abstract The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto’s paradox. Various implications for