Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
J Theor Biol. 2010 May 21;264(2):420-42. doi: 10.1016/j.jtbi.2010.02.023. Epub 2010 Feb 20.
A cell kinetics model is developed to describe the evolution of prostate cancer (PC) from diagnosis to PC specific death. Such a model can be used to estimate an individual's eventual outcome and thus to inform decisions about therapy. To describe the observed clinical progression, the model must postulate three PC cell populations that are (1) local to the prostate and sensitive to hormones, (2) regional and hormone sensitive, and (3) systemic and hormone resistant. A set of coupled first-order differential equations describes the exponential growth of a PC tumor as well as its transformation from a local to systemic disease. The time dependence of the solutions is scaled to the doubling time of the prostate specific antigen (PSADT) because it characterizes the tumor growth for the individual. The conversion from local to systemic cell populations is described with a parameter alpha that can be associated with the Gleason score. The model also has three critical cell populations that describe (1) the initiation of the non-local populations, (2) the saturation level of the local tumor, and (3) the cell count likely to cause PC specific death. These parameters are calibrated by reproducing published PC clinical data and survival tables. The model is then applied to individuals with complete PC diagnostic data in order to calculate the progression to PC specific death. One man has early stage PC as described in the 'vignette' patient of Walsh et al. (2007. N. Engl. J. Med. 357, 2696-2705). The second man has a more serious condition and has undergone both local and systemic treatments. Unfortunately, I am that patient.
建立了一个细胞动力学模型来描述前列腺癌（PC）从诊断到 PC 特异性死亡的演变。这样的模型可以用来估计个体的最终结果，从而为治疗决策提供信息。为了描述观察到的临床进展，该模型必须假设三种 PC 细胞群体，分别是（1）局部前列腺且对激素敏感，（2）区域性且对激素敏感，以及（3）系统性且对激素耐药。一组耦合的一阶微分方程描述了 PC 肿瘤的指数增长及其从局部疾病向系统性疾病的转变。解决方案的时间依赖性被缩放至前列腺特异性抗原（PSA）倍增时间（PSADT），因为它可以为个体的肿瘤生长提供特征。从局部到系统性细胞群体的转换用参数α来描述，该参数α可以与 Gleason 评分相关联。该模型还有三个关键的细胞群体，分别描述了（1）非局部细胞群体的起始，（2）局部肿瘤的饱和水平，以及（3）可能导致 PC 特异性死亡的细胞计数。通过重现发表的 PC 临床数据和生存表，对这些参数进行了校准。然后，该模型被应用于具有完整 PC 诊断数据的个体，以计算向 PC 特异性死亡的进展。一个人患有 Walsh 等人描述的早期 PC（2007. N. Engl. J. Med. 357, 2696-2705）的 vignette 患者。第二个男人的病情更严重，已经接受了局部和全身治疗。不幸的是，我就是那个病人。
