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标题: Inhibiting glutamine uptake represents an attractive new strat... [打印本页]

作者: liyongncu    时间: 2013-9-11 09:32
标题: Inhibiting glutamine uptake represents an attractive new strat...
题名Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia
链接http://www.ncbi.nlm.nih.gov/pubmed/24014241

本帖最后由 yanghai811228 于 2013-9-11 09:44 编辑

Blood. 2013 Sep 6. [Epub ahead of print]
Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia.
Willems L, Jacque N, Jacquel A, Neveux N, Trovati Maciel T, Lambert M, Schmitt A, Poulain L, Green AS, Uzunov M, Kosmider O, Radford-Weiss I, Moura IC, Auberger P, Ifrah N, Bardet V, Chapuis N, Lacombe C, Mayeux P, Tamburini J, Bouscary D.
Source
Unite Fonctionnelle d'Hematologie, Hopital Cochin, AP-HP, Paris, France;

Abstract
Cancer cells require nutrients and energy to adapt to increased biosynthetic activity and protein synthesis inhibition downstream of mTORC1 has shown promise as a possible therapy for acute myeloid leukemia (AML). Glutamine contributes to leucine import into cells, which controls the amino acid/Rag/mTORC1 signaling pathway. We show in our current study that glutamine removal inhibits mTORC1 and induces apoptosis in AML cells. The knockdown of the SLC1A5 high affinity transporter for glutamine induces apoptosis and inhibits tumor formation in a mouse AML xenotransplantation model. L-asparaginase (L-ase) is an anti-cancer agent also harboring glutaminase activity. We show that L-ases from both E. coli and E. chrysanthemi profoundly inhibit mTORC1 and protein synthesis and that this inhibition correlates with their glutaminase activity levels and produces a strong apoptotic response in primary AML cells. We further show that L-ases upregulate glutamine synthase (GS) expression in leukemic cells and that a GS knockdown enhances L-ase-induced apoptosis in some AML cells. Finally, we observe a strong autophagic process upon L-ase treatment. These results suggest that L-ase anti-cancer activity and glutamine uptake inhibition are promising new therapeutic strategies for AML.


作者: lo7ve77    时间: 2013-9-11 09:32
http://pan.baidu.com/share/link? ... 0&uk=1845660311
作者: lo7ve77    时间: 2013-9-11 09:32
本帖最后由 lo7ve77 于 2013-9-11 09:34 编辑

1111111111111111
下次请以文献题目作为帖子标题,无需多余加词!谢谢合作!
作者: liyongncu    时间: 2013-9-11 09:37
lo7ve77 发表于 2013-9-11 09:32
1111111111111111
下次请以文献题目作为帖子标题,无需多余加词!谢谢合作!

nod!谢谢提醒,第一次发帖,请多多指导!
作者: lo7ve77    时间: 2013-9-11 09:44
liyongncu 发表于 2013-9-11 09:37
nod!谢谢提醒,第一次发帖,请多多指导!

,看看版规,多发几次求助帖,就好了!
作者: liyongncu    时间: 2013-9-11 12:23
lo7ve77 发表于 2013-9-11 09:32
http://pan.baidu.com/share/link?shareid=747190170&uk=1845660311

Thanks a lot!




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