Ethynyldeoxyuridine (EdU) suppresses in vitro population expansion and in vivo tumor progression of human glioblastoma cells.
Ethynyldeoxyuridine (EdU) suppresses in vitro population expansion and in vivo tumor progression of human glioblastoma cells.
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DOI：
10.1007/s11060-011-0621-6
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发表时间：
2011-12
影响因子：
3.9
通讯作者：
Laywell, Eric D.
中科院分区：
文献类型：
--
作者：
Ross, Heather H.;Rahman, Maryam;Levkoff, Lindsay H.;Millette, Sebastien;Martin-Carreras, Teresa;Dunbar, Erin M.;Reynolds, Brent A.;Laywell, Eric D.
胸苷类似物（TA）是掺入新合成的DNA中的合成核苷。卤代嘧啶（HP），如溴脱氧尿苷（BrdU），是一类可以用抗体检测的TA，通常用于测定单个细胞的出生日期和评估细胞群的增殖指数。已经确定，HP在掺入DNA链中时可以充当放射增敏剂，但通常认为它们在不存在次级应激源的情况下不会损害正常细胞功能。然而，我们和其他人已经表明，HP掺入导致哺乳动物细胞中细胞周期进程的持续抑制，导致体细胞中的细胞衰老。此外，我们已经表明，HP掺入导致在胶质瘤的同基因大鼠模型中延迟肿瘤进展。在这里，我们研究乙炔脱氧尿苷（EdU），一个新开发的和烷基化的TA，其抗癌活性，在体外和体内。我们表明，EdU，像HP，导致在体外正常和转化细胞的增殖率严重下降。然而，与HP不同，EdU掺入也引起DNA损伤，导致大量经处理细胞亚群的死亡。当在较长时间内作为单一疗法施用给携带人多形性胶质母细胞瘤肿瘤的皮下异种移植物的小鼠时，EdU显著减小肿瘤体积并增加存活率，而没有明显的显著毒性。这些结果，结合EdU容易穿过血脑屏障的事实，支持继续研究EdU作为恶性脑肿瘤的潜在疗法。
Thymidine analogs (TAs) are synthetic nucleosides that incorporate into newly synthesized DNA. Halogenated pyrimidines (HPs), such as bromodeoxyuridine (BrdU), are a class of TAs that can be detected with antibodies and are commonly used for birthdating individual cells and for assessing the proliferative index of cell populations. It is well established that HPs can act as radiosensitizers when incorporated into DNA chains, but they are generally believed not to impair normal cell function in the absence of secondary stressors. However, we and others have shown that HP incorporation leads to a sustained suppression of cell cycle progression in mammalian cells, resulting in cellular senescence in somatic cells. In addition, we have shown that HP incorporation results in delayed tumor progression in a syngeneic rat model of glioma. Here we examine ethynyldeoxyuridine (EdU), a newly developed and alkylated TA, for its anti-cancer activity, both in vitro and in vivo. We show that EdU, like HPs, leads to a severe reduction in the proliferation rate of normal and transformed cells in vitro. Unlike HPs, however, EdU incorporation also causes DNA damage resulting in the death of a substantial subset of treated cells. When administered over an extended time as a monotherapy to mice bearing subcutaneous xenografts of human glioblastoma multiforme tumors, EdU significantly reduces tumor volume and increases survival without apparent significant toxicity. These results, combined with the fact that EdU readily crosses the blood–brain barrier, support the continued investigation of EdU as a potential therapy for malignant brain tumors.
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影响因子：
4.8
作者：
Chen, YZ;McPhie, DL;Neve, RL
通讯作者：
Neve, RL
DOI：
10.1016/s0360-3016(99)00122-4
发表时间：
1999-08-01
影响因子：
7
作者：
Groves, MD;Maor, MH;Levin, VA
通讯作者：
Levin, VA
影响因子：
3.9
作者：
Martinez, Ramon;Rohde, Veit;Schackert, Gabriele
通讯作者：
Schackert, Gabriele
人类细胞系的遗传学。 iii。将5-溴和5-二羟基尿苷掺入人类细胞的脱氧核糖核酸及其对辐射敏感性的影响。
DOI：
10.1084/jem.112.3.509
发表时间：
1960-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
DJORDJEVIC B;SZYBALSKI W
通讯作者：
SZYBALSKI W
影响因子：
3.5
作者：
Meneni, Srinivasarao;Ott, Ingo;Dembinski, Roman
通讯作者：
Dembinski, Roman