Mathematical model of BCG immunotherapy in superficial bladder cancer
Mathematical model of BCG immunotherapy in superficial bladder cancer
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DOI：
10.1007/s11538-007-9195-z
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发表时间：
2007-08-01
影响因子：
3.5
通讯作者：
Stone, Lewi
中科院分区：
文献类型：
--
作者：
Bunimovich-Mendrazitsky, Svetlana;Shochat, Eliezer;Stone, Lewi
卡介苗（BCG）的免疫治疗-牛分枝杆菌（M。牛）用于抗结核免疫-是临床上建立的用于治疗浅表膀胱癌的方法。然而，尽管有大量的生物学经验，但其作用方式尚未完全阐明。本文的目的是开发第一个数学模型，该模型描述了BCG治疗后膀胱中的肿瘤-免疫相互作用。数学分析的ODE模型确定多个平衡点，其稳定性，和分歧点。人们发现了有趣的双稳态机制，其中治疗有可能导致无肿瘤平衡或完全成熟的肿瘤，这仅取决于初始条件。注意估计参数和验证模型使用发表的数据取自体外，小鼠和人体研究。该模型表明，免疫治疗的强度必须保持在有限的范围内。虽然小的治疗水平可能无法清除肿瘤，但过大的治疗可能导致过度刺激的免疫系统，对患者产生危险的副作用。
Immunotherapy with Bacillus Calmette-Guerin (BCG)-an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization-is a clinically established procedure for the treatment of superficial bladder cancer. However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties, and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can lead to an over-stimulated immune system having dangerous side effects for the patient.