Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia.
Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia.
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DOI：
10.1371/journal.pone.0095885
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Symons M
中科院分区：
文献类型：
--
作者：
Miller IS;Didier S;Murray DW;Turner TH;Issaivanan M;Ruggieri R;Al-Abed Y;Symons M
胶质母细胞瘤是星形细胞瘤的最恶性和致命形式，患者的中位生存时间约为15个月。因此，重要的是确定新的治疗方法。越来越多的证据表明，小胶质细胞（专门的脑内巨噬细胞）在胶质母细胞瘤肿瘤的发展和进展中起着重要作用。在本文中，我们表明，小胶质细胞，除了刺激胶质母细胞瘤细胞的侵袭，也促进胶质母细胞瘤细胞增殖和抵抗电离辐射在体外。我们发现，semapimod是一种选择性干扰巨噬细胞和小胶质细胞功能的药物，可有效抑制小胶质细胞刺激的GL 261侵袭，而不影响血清刺激的胶质母细胞瘤细胞侵袭。Semapimod还抑制小胶质细胞刺激的胶质母细胞瘤细胞对辐射的抗性，但对小胶质细胞刺激的胶质母细胞瘤细胞增殖没有显著影响。我们还发现，脑内施用semapimod与辐射组合强烈增加了GL 261荷瘤动物的存活率，但在没有辐射的情况下没有显著益处。总之，我们的观察表明，semapimod通过靶向小胶质细胞和/或浸润性巨噬细胞使胶质母细胞瘤对电离辐射敏感。
Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also promote glioblastoma cell proliferation and resistance to ionizing radiation in vitro. We found that semapimod, a drug that selectively interferes with the function of macrophages and microglia, potently inhibits microglia-stimulated GL261 invasion, without affecting serum-stimulated glioblastoma cell invasion. Semapimod also inhibits microglia-stimulated resistance of glioblastoma cells to radiation, but has no significant effect on microglia-stimulated glioblastoma cell proliferation. We also found that intracranially administered semapimod strongly increases the survival of GL261 tumor-bearing animals in combination with radiation, but has no significant benefit in the absence of radiation. In conclusion, our observations indicate that semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia and/or infiltrating macrophages.
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影响因子：
29.4
作者：
Hommes, D;Van Den Blink, B;Van Deventer, S
通讯作者：
Van Deventer, S
影响因子：
5.7
作者：
Coniglio, Salvatore J.;Eugenin, Eliseo;Segall, Jeffrey E.
通讯作者：
Segall, Jeffrey E.
DOI：
10.1073/pnas.93.9.3967
发表时间：
1996-04-30
影响因子：
11.1
作者：
Cohen, PS;Nakshatri, H;Tracey, KJ
通讯作者：
Tracey, KJ
影响因子：
24.5
作者：
Dotan, Iris;Rachmilewitz, Daniel;Hommes, Daniel
通讯作者：
Hommes, Daniel
影响因子：
4.4
作者：
Löwenberg, M;Verhaar, A;Hommes, D
通讯作者：
Hommes, D