Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.
Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.
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DOI：
10.1038/ncomms5632
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发表时间：
2014-08-18
影响因子：
16.6
通讯作者：
Soucek, Laura
中科院分区：
文献类型：
--
作者：
Annibali, Daniela;Whitfield, Jonathan R.;Favuzzi, Emilia;Jauset, Toni;Serrano, Erika;Cuartas, Isabel;Redondo-Campos, Sara;Folch, Gerard;Gonzalez-Junca, Alba;Sodir, Nicole M.;Masso-Valles, Daniel;Beaulieu, Marie-Eve;Swigart, Lamorna B.;Mc Gee, Margaret M.;Somma, Maria Patrizia;Nasi, Sergio;Seoane, Joan;Evan, Gerard I.;Soucek, Laura
胶质瘤是最常见的影响成人中枢神经系统的原发肿瘤，对标准治疗的反应很差。MYC与大多数人类肿瘤有因果关系，大多数胶质母细胞瘤Myc水平升高。利用Myc显性阴性Oomyc，我们先前证明Myc抑制是一种很有前途的癌症治疗策略。在这里，我们使用自发性多灶性侵袭性星形细胞瘤及其衍生的神经前体细胞、人脑胶质母细胞瘤细胞系和患者来源的体外和原位异种移植瘤的小鼠模型，在临床前验证Myc抑制作为一种治疗策略在小鼠和人脑胶质瘤中的作用。在所有这些实验模型中，我们发现Myc抑制抑制增殖，增加凋亡，并显著地诱导多核细胞的形成，这些细胞随后因有丝分裂灾难而停滞或死亡，揭示了Myc在胶质瘤细胞精准分裂中的新作用。MYC与多种癌症的发生有关。在这里，作者探索了Myc抑制在小鼠和人类胶质母细胞瘤模型中的治疗潜力和作用机制，胶质母细胞瘤是一种侵袭性类型的肿瘤，通常对常规治疗具有抵抗力。
Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells. Myc has been implicated in the development of multiple types of cancer. Here, the authors explore the therapeutic potential and mechanism of action of Myc inhibition in mouse and human models of glioblastoma, an aggressive type of tumour that is often resistant to conventional therapy.
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影响因子：
3.7
作者：
Bidwell GL 3rd;Perkins E;Hughes J;Khan M;James JR;Raucher D
通讯作者：
Raucher D
影响因子：
7.4
作者：
Mondol, Abdus S.;Tonks, Nicholas K.;Kamata, Tohru
通讯作者：
Kamata, Tohru
影响因子：
6
作者：
Shannon, P;Sabha, N;Guha, A
通讯作者：
Guha, A
DOI：
10.1126/science.1212728
发表时间：
2012-01-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kessler JD;Kahle KT;Sun T;Meerbrey KL;Schlabach MR;Schmitt EM;Skinner SO;Xu Q;Li MZ;Hartman ZC;Rao M;Yu P;Dominguez-Vidana R;Liang AC;Solimini NL;Bernardi RJ;Yu B;Hsu T;Golding I;Luo J;Osborne CK;Creighton CJ;Hilsenbeck SG;Schiff R;Shaw CA;Elledge SJ;Westbrook TF
通讯作者：
Westbrook TF
影响因子：
64.8
作者：
Soucek, Laura;Whitfield, Jonathan;Martins, Carla P.;Finch, Andrew J.;Murphy, Daniel J.;Sodir, Nicole M.;Karnezis, Anthony N.;Swigart, Lamorna Brown;Nasi, Sergio;Evan, Gerard I.
通讯作者：
Evan, Gerard I.