Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies.
Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies.
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DOI：
10.1038/sj.bjc.6604943
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发表时间：
2009-03-24
影响因子：
8.8
通讯作者：
Montero, E.
中科院分区：
文献类型：
--
作者：
Miqueli, A. Diaz;Rolff, J.;Lemm, M.;Fichtner, I.;Perez, R.;Montero, E.
由于表皮生长因子受体（EGFR）已被报道是一种辐射反应调节剂，HER抑制剂被认为是潜在的放射增敏剂。我们的研究探讨了尼妥珠单抗和西妥昔单抗的作用，两个单克隆抗体（单克隆抗体）EGFR，作为放射增敏剂在鼠胶质瘤模型在体内。两种抗体与放射的共同施用增加了U87 MG的放射敏感性，导致皮下（s.c.）肿瘤生长此外，在放射中加入抗体可减小脑肿瘤的大小，并抑制放射治疗引起的肿瘤细胞侵袭增加40-80%，尽管促进了肿瘤细胞凋亡。而尼妥珠单抗导致肿瘤血管的大小和皮下增殖细胞的减少。在肿瘤中，西妥昔单抗没有显著的抗血管生成或抗增殖活性。相比之下，西妥昔单抗与尼妥珠单抗相比诱导了更显著的EGFR下游信号传导抑制。此外，两种抗体都减少了放射抗性CD 133+癌症干细胞（CSC）的总数。这些结果是令人鼓舞的，并显示EGFR的mAb和放射的联合治疗优于针对多形性胶质母细胞瘤（GBM）的每种单一疗法，证实了这些药物作为人GBM中的放射增敏剂的作用。此外，我们首次显示了针对EGFR的mAb特异性靶向放射抗性胶质瘤CSC的能力，支持了在患者中的潜在用途。
As epidermal growth factor receptor (EGFR) has been reported to be a radiation response modulator, HER inhibitors are regarded to act as potential radiosensitisers. Our study examined the role of nimotuzumab and cetuximab both, the two monoclonal antibodies (mAbs) to EGFR, as radiosensitisers in a murine glioma model in vivo. Co-administration of both the antibodies with radiation increased the radiosensitivity of U87MG, resulting in a significant delay of subcutaneous (s.c.) tumour growth. Furthermore, the addition of antibodies to the radiation decreased brain tumour sizes and is inhibited by 40–80% the increased tumour cell invasion provoked by radiotherapy, although promoted tumour cell apoptosis. Whereas nimotuzumab led to a reduction in the size of tumour blood vessels and proliferating cells in s.c. tumours, cetuximab had no significant antiangiogenic nor antiproliferative activity. In contrast, cetuximab induced a more marked inhibition of EGFR downstream signalling compared with nimotuzumab. Moreover, both antibodies reduced the total number of radioresistant CD133+ cancer stem cells (CSCs). These results were encouraging, and showed the superiority of combined treatment of mAbs to EGFR and radiation over each single therapy against glioblastoma multiforme (GBM), confirming the role of these drugs as radiosensitisers in human GBM. In addition, we first showed the ability of mAb specifics against EGFR to target radioresistant glioma CSC, supporting the potential use in patients.
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DOI：
10.1016/j.ijrobp.2004.01.053
发表时间：
2004-01-01
影响因子：
7
作者：
Bonner, JA;Buchsbaum, DJ;Raisch, KP
通讯作者：
Raisch, KP
影响因子：
--
作者：
Miqueli, Arlhee Diaz;Blanco, Rances;Montero, Enrique
通讯作者：
Montero, Enrique
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
4.8
作者：
Eller, JL;Longo, SL;Canute, GW
通讯作者：
Canute, GW
影响因子：
11.5
作者：
Lamszus, K;Brockmann, MA;Westphal, M
通讯作者：
Westphal, M