An on-lattice agent-based Monte Carlo model simulating the growth kinetics of multicellular tumor spheroids |
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| Institution: | 1. Servicio de Oncología Radioterápica, Hospital Universitario Marqués de Valdecilla, E-39008 Santander, Spain;2. Servicio de Radiofísica y Protección Radiológica, Hospital Universitario Dr. Negrín, E-35010 Gran Canaria, Spain;3. Unidad de Radiofísica, Hospital Universitario San Cecilio, E-18016 Granada, Spain;4. Instituto de Investigación Biosanitaria (ibs.GRANADA), Complejo Hospitalario Universitario de Granada/Universidad de Granada, E-18016 Granada, Spain;5. Departamento de Radiología y Medicina Física, Universidad de Granada, E-18071 Granada, Spain;6. Instituto de Biopatología y Medicina Regenerativa (IBIMER), Universidad de Granada, E-18071 Granada, Spain;7. Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, E-18071 Granada, Spain;1. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea;2. Department of Radiation Oncology, Samsung Medical Centre, Seoul 06351, Republic of Korea;1. Department of Radiation Oncology, Medical University Vienna, Austria;2. Division of Radiation Therapy, Department of Diagnostic and Therapeutic Radiology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;3. University of Applied Science Wiener, Neustadt, Austria;4. MedAustron Ion Therapy Center, Wiener Neustadt, Austria;1. Cockcroft Institute, Warrington WA4 4AD, United Kingdom;2. University of Liverpool, Merseyside L69 3BX, United Kingdom;3. The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral CH63 4JY, United Kingdom;4. University College London, University of London, London WC1E 6BT, United Kingdom;5. John Adams Institute at Royal Holloway, University of London, Egham TW20 0EX, United Kingdom;1. Corporate Research and Development Center, Toshiba Corporation, Kanagawa 212 8582, Japan;2. Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263 8555, Japan;1. Department of Medical Physics, Greater Poland Cancer Centre, Poznań, Poland;2. Department of Technical Physics, Poznan University of Technology, Poznań, Poland;3. Medical Physics & Clinical Engineering, Nottingham University Hospitals NHS Trust, Nottingham, UK;4. School of Medicine, University of Nottingham, Nottingham, UK;5. Department of Electroradiology, Poznań University of Medical Sciences, Poznań, Poland |
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| Abstract: | PurposeTo develop an on-lattice agent-based model describing the growth of multicellular tumor spheroids using simple Monte Carlo tools.MethodsCells are situated on the vertices of a cubic grid. Different cell states (proliferative, hypoxic or dead) and cell evolution rules, driven by 10 parameters, and the effects of the culture medium are included. About twenty spheroids of MCF-7 human breast cancer were cultivated and the experimental data were used for tuning the model parameters.ResultsSimulated spheroids showed adequate sizes of the necrotic nuclei and of the hypoxic and proliferative cell phases as a function of the growth time, mimicking the overall characteristics of the experimental spheroids. The relation between the radii of the necrotic nucleus and the whole spheroid obtained in the simulations was similar to the experimental one and the number of cells, as a function of the spheroid volume, was well reproduced. The statistical variability of the Monte Carlo model described the whole volume range observed for the experimental spheroids. Assuming that the model parameters vary within Gaussian distributions it was obtained a sample of spheroids that reproduced much better the experimental findings.ConclusionsThe model developed allows describing the growth of in vitro multicellular spheroids and the experimental variability can be well reproduced. Its flexibility permits to vary both the agents involved and the rules that govern the spheroid growth. More general situations, such as, e. g., tumor vascularization, radiotherapy effects on solid tumors, or the validity of the tumor growth mathematical models can be studied. |
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| Keywords: | Tumor growth Multicellular spheroids On-lattice agent-based model Monte Carlo |
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