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有丝分裂灾难是导致碳离子敏感性与顺铂之间弱相关性的一种假设机制。

Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin.

机构信息

Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.

Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.

出版信息

Sci Rep. 2017 Jan 16;7:40588. doi: 10.1038/srep40588.

Abstract

In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4',6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.

摘要

在当今的癌症治疗中,碳离子放疗主要作为单一疗法使用,而顺铂则与 X 射线放疗同时使用。碳离子与顺铂同时使用的效果尚不清楚。为了获得碳离子或 X 射线和顺铂之间可能存在的共同作用机制的信息,我们评估了单一治疗的敏感性相关性。在 20 个人类癌细胞系中,对 X 射线的敏感性与对顺铂的敏感性强烈相关,表明存在潜在的共同作用靶机制。有趣的是,碳离子与顺铂的敏感性相关性比 X 射线和顺铂的敏感性相关性弱得多,表明碳离子和顺铂之间存在潜在的不同作用靶机制。通过 4',6-二脒基-2-苯基吲哚二盐酸盐染色评估集落形成细胞死亡表明,有丝分裂灾难比相同物理剂量的 X 射线更有效地由碳离子诱导,而凋亡和衰老则没有。这些数据表明,碳离子和顺铂的敏感性相关性比 X 射线和顺铂的敏感性相关性弱,这有助于作为理解这些治疗方法之间潜在共同机制的生物学基础。进一步的研究是阐明碳离子和顺铂联合应用的临床疗效所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dff/5238371/f98f0ec38ca9/srep40588-f1.jpg

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