A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent.
A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent.
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DOI：
10.1371/journal.pone.0199130
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Ahuja N
中科院分区：
文献类型：
--
作者：
Thakar M;Hu Y;Morreale M;Lerner L;Ying Lin W;Sen R;Cai Y;Karunasena E;Thakar M;Saggi S;Keer H;Ahuja N
预计到2030年，胰腺导管腺癌（PDAC）将成为癌症死亡率的第二大原因。PDAC仍然对大多数全身化疗具有耐药性。在本文中，我们探讨表观遗传增敏是否可以改善PDAC的化疗反应。用系列浓度的表观遗传调节剂5-阿扎胞苷（Aza）和胍地西他滨（SGI-110）测试多个PDAC细胞系。胍地西他滨在纳摩尔浓度下有效抑制DNA甲基转移酶1（DNMT 1）的表达并降低细胞活力。我们还报告说，guadecitabine增加了延迟期后的疗效，或作为我们的参考，“休息期”。胍地他滨的敏化作用改善了对化疗药物-伊立替康的反应，如通过降低细胞活力和伴随半胱天冬酶活性增加所测量的。需要进一步的研究来了解作用机制。
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second leading cause of cancer mortality by 2030. PDAC remains resistant to the majority of systemic chemotherapies. In this paper, we explore if epigenetic sensitization can improve chemotherapy response in PDAC. Multiple PDAC cell lines were tested with serial concentrations of the epigenetic modulators 5-azacitidine (Aza) and guadecitabine (SGI-110). Guadecitabine was effective at inhibiting the expression of DNA Methyltransferase 1 (DNMT1) and in decreasing cell viability at nanomolar concentrations. We also report that guadecitabine has increased efficacy following a delay period or as we reference, a ‘rest period’. Sensitization with guadecitabine improved response to the chemotherapeutic agent–Irinotecan- as measured by decreased cell viability and accompanied by an increase in caspase activity. Additional studies are needed to understand the mechanism of action.
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影响因子：
7
作者：
Cai Y;Tsai HC;Yen RC;Zhang YW;Kong X;Wang W;Xia L;Baylin SB
通讯作者：
Baylin SB
影响因子：
28.2
作者：
Clozel T;Yang S;Elstrom RL;Tam W;Martin P;Kormaksson M;Banerjee S;Vasanthakumar A;Culjkovic B;Scott DW;Wyman S;Leser M;Shaknovich R;Chadburn A;Tabbo F;Godley LA;Gascoyne RD;Borden KL;Inghirami G;Leonard JP;Melnick A;Cerchietti L
通讯作者：
Cerchietti L
影响因子：
7
作者：
Easwaran, Hariharan;Johnstone, Sarah E.;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.
影响因子：
6.2
作者：
Fu, Siqing;Hu, Wei;Iyer, Revathy;Kavanagh, John J.;Coleman, Robert L.;Levenback, Charles F.;Sood, Anil K.;Wolf, Judith K.;Gershenson, David M.;Markman, Maurie;Hennessy, Bryan T.;Kurzrock, Razelle;Bast, Robert C., Jr.
通讯作者：
Bast, Robert C., Jr.
DOI：
10.1016/s1470-2045(17)30576-4
发表时间：
2017-10
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Kantarjian HM;Roboz GJ;Kropf PL;Yee KWL;O'Connell CL;Tibes R;Walsh KJ;Podoltsev NA;Griffiths EA;Jabbour E;Garcia-Manero G;Rizzieri D;Stock W;Savona MR;Rosenblat TL;Berdeja JG;Ravandi F;Rock EP;Hao Y;Azab M;Issa JJ
通讯作者：
Issa JJ