A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas.
A critical role for choline kinase-alpha in the aggressiveness of bladder carcinomas.
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DOI：
10.1038/onc.2009.91
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发表时间：
2009-07-02
期刊：
影响因子：
8
通讯作者：
de Molina, A. Ramirez
中科院分区：
文献类型：
--
作者：
Hernando, E.;Sarmentero-Estrada, J.;Koppie, T.;Belda-Iniesta, C.;de Molina, V. Ramirez;Cejas, P.;Ozu, C.;Le, C.;Sanchez, J. J.;Gonzalez-Baron, M.;Koutcher, J.;Cordon-Cardo, C.;Bochner, B. H.;Lacal, J. C.;de Molina, A. Ramirez
膀胱癌是工业化国家最常见的死亡原因之一。新的肿瘤标志物和治疗方法仍然需要改善膀胱癌患者的管理。胆碱激酶α (ChoKα)是一种代谢酶，在细胞增殖和转化中起作用。ChoKα抑制剂显示抗肿瘤活性，有望很快进入临床试验。本研究旨在评估ChoKα是否在膀胱肿瘤侵袭性中发挥作用，并为膀胱癌的治疗提供新的途径。我们在这里证明了ChoKα在人膀胱肿瘤细胞中是组成性改变的。此外，包括原位模型在内的体内小鼠模型尽可能地模拟生理条件，揭示了ChoKα水平的升高在不同终点上增强了肿瘤形成（p≤0.0001）和疾病的侵袭性（p=0.011）。因此，ChoKα水平升高可显著降低膀胱癌小鼠的存活率（p=0.05）。最后，用ChoKα特异性抑制剂治疗可显著抑制肿瘤生长（p=0.02），并相应提高生存期（p=0.03）。
Bladder cancer is one of the most common causes of death in industrialized countries. New tumor markers and therapeutic approaches are still needed to improve management of bladder cancer patients. Choline Kinase alpha (ChoKα) is a metabolic enzyme that has a role in cell proliferation and transformation. Inhibitors of ChoKα display antitumoral activity and are expected to be soon in clinical trials. This study is aimed to asses whether ChoKα plays a role in the aggressiveness of bladder tumors and constitute a new approach for bladder cancer treatment. We demonstrate here that ChoKα is constitutively altered in human bladder tumor cells. Furthermore, in vivo murine models including an orthotopic model to mimic as much as possible the physiological conditions, revealed that increased levels of ChoKα potentiates both tumor formation (p≤0.0001) and aggressiveness of the disease over different endpoints (p=0.011). Accordingly, increased levels of ChoKα significantly reduces survival of mice with bladder cancer (p=0.05). Finally, treatment with ChoKα specific inhibitor resulted in a significant inhibition of tumor growth (p=0.02) and in a relevant increase in survival (p=0.03).
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影响因子：
11.5
作者：
Kikuchi, E;Menendez, S;Bochner, BH
通讯作者：
Bochner, BH
DOI：
10.1016/s0006-291x(02)00920-8
发表时间：
2002-08-23
影响因子：
3.1
作者：
Ramírez de Molina, A;Rodríguez-González, A;Lacal, JC
通讯作者：
Lacal, JC
影响因子：
51.1
作者：
Ramirez de Molina, Ana;Sormentero-Estrada, Jacinto;Lacal, Juan Carlos
通讯作者：
Lacal, Juan Carlos
影响因子：
8
作者：
Rodríguez-González, A;de Molina, AR;Lacal, JC
通讯作者：
Lacal, JC
影响因子：
11.2
作者：
Al-Saffar, NMS;Troy, H;Chung, YL
通讯作者：
Chung, YL