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新型喜树碱类似物NSC606985在急性早幼粒细胞白血病小鼠模型中的治疗效果

Therapeutic efficacy of NSC606985, a novel camptothecin analog, in a mouse model of acute promyelocytic leukemia.

作者信息

Liu Wei, Zhu Yuan-Shan, Guo Meng, Yu Yun, Chen Guo-Qiang

机构信息

Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.

出版信息

Leuk Res. 2007 Nov;31(11):1565-74. doi: 10.1016/j.leukres.2007.03.011. Epub 2007 Apr 10.

DOI:10.1016/j.leukres.2007.03.011
PMID:17428537
Abstract

Nanomolar concentrations of NSC606985, a novel camptothecin (CPT) analog, effectively induces apoptosis in vitro in acute myeloid leukemic (AML) cells. Here we investigated the potential therapeutic effects of NSC606985 on the mice model with acute promyelocytic leukaemia (APL), a unique subtype of AML. The results showed that NSC606985 at single dose rapidly eliminated the infiltration with apoptosis induction of leukemic cells in peripheral blood and tissues. Treatment of NSC606985 with two regimens, continuous monotherapy and intermittent long-term therapy, significantly prolonged the survival of leukemic mice with tumor regression. These results propose that NSC606985 warrants further preclinical and clinical investigations for AML treatment.

摘要

新型喜树碱(CPT)类似物NSC606985的纳摩尔浓度能在体外有效诱导急性髓系白血病(AML)细胞凋亡。在此,我们研究了NSC606985对急性早幼粒细胞白血病(APL,AML的一种独特亚型)小鼠模型的潜在治疗效果。结果显示,单剂量的NSC606985能迅速消除外周血和组织中白血病细胞的浸润并诱导其凋亡。采用连续单一疗法和间歇性长期疗法这两种方案使用NSC606985进行治疗,能显著延长白血病小鼠的生存期并使肿瘤消退。这些结果表明,NSC606985在AML治疗方面值得进一步开展临床前和临床研究。

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1
Therapeutic efficacy of NSC606985, a novel camptothecin analog, in a mouse model of acute promyelocytic leukemia.新型喜树碱类似物NSC606985在急性早幼粒细胞白血病小鼠模型中的治疗效果
Leuk Res. 2007 Nov;31(11):1565-74. doi: 10.1016/j.leukres.2007.03.011. Epub 2007 Apr 10.
2
Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cdelta-dependent mechanisms.喜树碱类似物NSC606985的纳摩尔浓度通过蛋白激酶Cδ依赖性机制诱导白血病细胞凋亡。
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引用本文的文献

1
Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer?喜树碱(CPT)及其衍生物已知以拓扑异构酶I(Top1)为作用靶点:在用于治疗癌症等人类疾病的喜树碱类似物分子靶点方面,我们是否遗漏了什么?
Am J Cancer Res. 2017 Dec 1;7(12):2350-2394. eCollection 2017.
2
Anti-proliferative and apoptosis-inducing effects of camptothecin-20(s)-O-(2-pyrazolyl-1)acetic ester in human breast tumor MCF-7 cells.喜树碱-20(s)-O-(2-吡唑基-1)乙酸酯对人乳腺癌MCF-7细胞的抗增殖和诱导凋亡作用。
Molecules. 2014 Apr 17;19(4):4941-55. doi: 10.3390/molecules19044941.
3
Camptothecin-20(s)-O-[N-(3'α,12'α-dihydroxy-24'-carbonyl-5'β-cholan)]-lysine, a novel camptothecin analogue, induces apoptosis towards hepatocellular carcinoma SMMC-7721 cells.
喜树碱-20(s)-O-[N-(3'α,12'α-二羟基-24'-羰基-5'β-胆烷)]-赖氨酸,一种新型喜树碱类似物,诱导肝癌 SMMC-7721 细胞凋亡。
Molecules. 2011 Sep 13;16(9):7803-14. doi: 10.3390/molecules16097803.
4
Protein kinase Cdelta stimulates proteasome-dependent degradation of C/EBPalpha during apoptosis induction of leukemic cells.蛋白激酶 Cδ在白血病细胞凋亡诱导过程中刺激蛋白酶体依赖性的 C/EBPα降解。
PLoS One. 2009 Aug 7;4(8):e6552. doi: 10.1371/journal.pone.0006552.
5
NSC606985, a novel camptothecin analog, induces apoptosis and growth arrest in prostate tumor cells.新型喜树碱类似物NSC606985可诱导前列腺肿瘤细胞凋亡并使其生长停滞。
Cancer Chemother Pharmacol. 2009 Jan;63(2):303-12. doi: 10.1007/s00280-008-0740-8. Epub 2008 Mar 29.