Department of Computer Science and Mathematics, Ariel University, Ariel 40700, Israel.
V.A. Negovsky Research Institute for General Reanimatology, 25 Petrovka, Bldg. 2, Moscow 107035, Russian Federation; D. Rogachev Federal Clinical Research Center for Children Hematology, Oncology and Immunology, 1 Samory Mashela St., Moscow 117198, Russian Federation; University of Nebraska Medical Center, Omaha, NE 68198, USA.
Comput Biol Med. 2015 Mar;58:118-29. doi: 10.1016/j.compbiomed.2014.12.022. Epub 2015 Jan 5.
In this work, we present a mathematical model of the initiation and progression of a low-grade urinary bladder carcinoma. We simulate the crucial processes affecting tumor growth, such as oxygen diffusion, carcinogen penetration, and angiogenesis, within the framework of the urothelial cell dynamics. The cell dynamics are modeled using the discrete technique of cellular automata, while the continuous processes of carcinogen penetration and oxygen diffusion are described by nonlinear diffusion-absorption equations. As the availability of oxygen is necessary for tumor progression, processes of oxygen transport to the tumor growth site seem most important. Our model yields a theoretical insight into the main stages of development and growth of urinary bladder carcinoma with emphasis on the two most common types: bladder polyps and carcinoma in situ. Analysis of histological structure of bladder tumor is important to avoid misdiagnosis and wrong treatment. We expect our model to be a valuable tool in the study of bladder cancer progression due to the exposure to carcinogens and the oxygen dependent expression of genes promoting tumor growth. Our numerical simulations have good qualitative agreement with in vivo results reported in the corresponding medical literature.
在这项工作中,我们提出了一个低级别膀胱癌发生和发展的数学模型。我们在尿路上皮细胞动力学的框架内模拟了影响肿瘤生长的关键过程,如氧扩散、致癌物渗透和血管生成。细胞动力学使用细胞自动机的离散技术进行建模,而致癌物渗透和氧扩散的连续过程则用非线性扩散-吸收方程来描述。由于肿瘤进展需要氧气,因此向肿瘤生长部位输送氧气的过程似乎最为重要。我们的模型深入了解了膀胱癌发展和生长的主要阶段,重点关注两种最常见的类型:膀胱息肉和原位癌。对膀胱癌的组织学结构进行分析对于避免误诊和错误治疗非常重要。我们预计,由于暴露于致癌物质和促进肿瘤生长的基因的氧依赖性表达,我们的模型将成为膀胱癌进展研究的一个有价值的工具。我们的数值模拟与相应医学文献中报道的体内结果具有良好的定性一致性。