Braunschweig Integrated Centre of Systems Biology and Helmholtz Center for Infectious Research, Braunschweig, Germany.
Center for Information Services and High Performance Computing, Technische Universität Dresden, Germany.
Sci Rep. 2016 Nov 23;6:37283. doi: 10.1038/srep37283.
Gliomas are highly invasive brain tumours characterised by poor prognosis and limited response to therapy. There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve tumour blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation induced by blood vessel occlusion/collapse. In contrast, the therapeutic intention of normalising the abnormal tumour vasculature is to improve the efficacy of conventional treatment modalities. Although these strategies have shown therapeutic potential, it remains unclear why they both often fail to control glioma growth. To shed some light on this issue, we propose a mathematical model based on the migration/proliferation dichotomy of glioma cells in order to investigate why vaso-modulatory interventions have shown limited success in terms of tumour clearance. We found the existence of a critical cell proliferation/diffusion ratio that separates glioma responses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the front speed and increase the infiltration width, for those in the other regime, the invasion speed increases and infiltration width decreases. We discuss how these in silico findings can be used to guide individualised vaso-modulatory approaches to improve treatment success rates.
神经胶质瘤是高度侵袭性的脑肿瘤,其预后较差,对治疗的反应有限。针对神经胶质瘤侵袭的血管调节干预的治疗潜力存在持续争论。突出的血管靶向治疗涉及肿瘤血管恶化和正常化。前者旨在通过血管闭塞/塌陷引起肿瘤梗死和营养剥夺。相比之下,使异常肿瘤血管正常化的治疗意图是提高常规治疗方式的疗效。尽管这些策略显示出治疗潜力,但尚不清楚为什么它们都常常无法控制神经胶质瘤的生长。为了解决这个问题,我们提出了一个基于神经胶质瘤细胞迁移/增殖二分法的数学模型,以研究为什么血管调节干预在肿瘤清除方面的效果有限。我们发现存在一个临界细胞增殖/扩散比,将神经胶质瘤对血管调节干预的反应分为两个截然不同的状态。对于属于一个状态的肿瘤,血管调节会降低前沿速度并增加渗透宽度,而对于属于另一个状态的肿瘤,入侵速度增加,渗透宽度减小。我们讨论了如何将这些计算机模拟结果用于指导个体化的血管调节方法,以提高治疗成功率。