Synergistic activity of rapamycin and dexamethasone in vitro and in vivo in acute lymphoblastic leukemia via cell-cycle arrest and apoptosis.
Synergistic activity of rapamycin and dexamethasone in vitro and in vivo in acute lymphoblastic leukemia via cell-cycle arrest and apoptosis.
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DOI：
10.1016/j.leukres.2011.10.022
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发表时间：
2012-03
影响因子：
2.7
通讯作者：
Kang MH
中科院分区：
文献类型：
--
作者：
Zhang C;Ryu YK;Chen TZ;Hall CP;Webster DR;Kang MH
磷酸酶和张力蛋白同源物（PTEN）突变后mTOR通路的激活可能与急性淋巴细胞白血病（ALL）中糖皮质激素（GC）抵抗相关。测定雷帕霉素和地塞米松在ALL细胞系和异种移植模型中的组合活性。与单独使用任何一种药物相比，地塞米松+雷帕霉素在某些细胞系中显示出显著更大的凋亡和细胞周期阻滞，这在具有PTEN突变的T系细胞系中更常见。该组合显著延长了携带PTEN突变异种移植物的小鼠的无事件生存期。我们的数据表明，PI 3 K/mTOR通路抑制剂可以使PTEN突变的T-ALL患者受益。
Activation of the mTOR pathway subsequent to phosphatase and tensin homolog (PTEN) mutation may be associated with glucocorticoid (GC) resistance in acute lymphoblastic leukemia (ALL). The combination activity of rapamycin and dexamethasone in cell lines and xenograft models of ALL was determined. Compared with either drug alone, dexamethasone + rapamycin showed significantly greater apoptosis and cell cycle arrest in some cell lines, which was more frequently seen in T-lineage cell lines with PTEN mutation. The combination significantly extended the event-free survival of mice carrying PTEN mutated xenografts. Our data suggest that PI3K/mTOR pathway inhibitors could benefit patients with PTEN mutated T-ALL.
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影响因子：
45.3
作者：
Chan, S;Scheulen, ME;Moore, L
通讯作者：
Moore, L
影响因子：
11.4
作者：
Pieters, R;den Boer, ML;Veerman, AJP
通讯作者：
Veerman, AJP
影响因子：
5.3
作者：
Fingar, DC;Richardson, CJ;Blenis, J
通讯作者：
Blenis, J
影响因子：
20.3
作者：
Gutierrez, Alejandro;Sanda, Takaomi;Look, A. Thomas
通讯作者：
Look, A. Thomas
影响因子：
8.8
作者：
Beesley, A. H.;Firth, M. J.;Ford, J.;Weller, R. E.;Freitas, J. R.;Perera, K. U.;Kees, U. R.
通讯作者：
Kees, U. R.