Hypoxia inducible factors-mediated inhibition of cancer by GM-CSF: a mathematical model.
Hypoxia inducible factors-mediated inhibition of cancer by GM-CSF: a mathematical model.
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DOI：
10.1007/s11538-012-9776-3
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发表时间：
2012-11
影响因子：
3.5
通讯作者：
Friedman, Avner
中科院分区：
文献类型：
--
作者：
Chen, Duan;Roda, Julie M.;Marsh, Clay B.;Eubank, Timothy D.;Friedman, Avner
在缺氧条件下，肿瘤细胞和肿瘤相关巨噬细胞产生VEGF（血管内皮生长因子），一种诱导血管生成的信号分子。当用GM-CSF（粒细胞/巨噬细胞集落刺激因子）处理时，相同的巨噬细胞产生sVEGFR-1（可溶性VEGF受体-1），sVEGFR-1是一种与VEGF结合并使其功能失活的可溶性蛋白。巨噬细胞产生VEGF受HIF-1α（缺氧诱导因子-1 α）调节，sVEGFR-1的产生受HIF-2α介导。最近的实验测量了GM-CSF治疗在具有HIF-1α缺陷或HIF-2α缺陷巨噬细胞的小鼠中抑制肿瘤生长的效果。在本文中，我们代表这些实验的数学模型的基础上的一个系统的偏微分方程。我们表明，模型模拟符合上述实验。然后，该模型可用于建议抑制肿瘤生长的策略。例如，该模型定性预测GM-CSF治疗与稳定HIF-2α的小分子抑制剂组合将减少肿瘤体积和血管生成的程度。
Under hypoxia, tumor cells, and tumor-associated macrophages produce VEGF (vascular endothelial growth factor), a signaling molecule that induces angiogenesis. The same macrophages, when treated with GM-CSF (granulocyte/macrophage colony-stimulating factor), produce sVEGFR-1 (soluble VEGF receptor-1), a soluble protein that binds with VEGF and inactivates its function. The production of VEGF by macrophages is regulated by HIF-1α (hypoxia inducible factor-1α), and the production of sVEGFR-1 is mediated by HIF-2α. Recent experiments measured the effect of inhibiting tumor growth by GM-CSF treatment in mice with HIF-1α-deficient or HIF-2α-deficient macrophages. In the present paper, we represent these experiments by a mathematical model based on a system of partial differential equations. We show that the model simulations agree with the above experiments. The model can then be used to suggest strategies for inhibiting tumor growth. For example, the model qualitatively predicts the extent to which GM-CSF treatment in combination with a small molecule inhibitor that stabilizes HIF-2α will reduce tumor volume and angiogenesis.
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影响因子：
2
作者：
Owen, MR;Byrne, HM;Lewis, CE
通讯作者：
Lewis, CE
影响因子：
11.2
作者：
Eubank TD;Roberts RD;Khan M;Curry JM;Nuovo GJ;Kuppusamy P;Marsh CB
通讯作者：
Marsh CB
影响因子：
4.4
作者：
Eubank, TD;Galloway, M;Marsh, CB
通讯作者：
Marsh, CB
影响因子：
20.3
作者：
Eubank, Tim D.;Roda, Julie M.;Marsh, Clay B.
通讯作者：
Marsh, Clay B.
影响因子：
5
作者：
Lawicki, Slawomir;Szmitkowski, Maciej;Wojtukiewicz, Marek
通讯作者：
Wojtukiewicz, Marek