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染色质、癌症与药物疗法。

Chromatin, cancer and drug therapies.

作者信息

Cortez Connie C, Jones Peter A

机构信息

Department of Urology, University of Southern California, Los Angeles, CA 90089-9181, USA.

出版信息

Mutat Res. 2008 Dec 1;647(1-2):44-51. doi: 10.1016/j.mrfmmm.2008.07.006. Epub 2008 Jul 22.

DOI:10.1016/j.mrfmmm.2008.07.006
PMID:18691602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2631123/
Abstract

The structure and organization of chromatin have attracted a great deal of attention recently because of their implications for the field of epigenetics. DNA methylation and the post-translational modifications that occur on histones can specify transcriptional competency. During cancer development, tumor suppressor genes become silenced by DNA hypermethylation and chromatin modifiers no longer perform in their usual manner. Current epigenetic therapy has been able to take advantage of the reversibility of these epimutations. Progress has been made in the treatment of hematological malignancies and some solid tumors. As the knowledge of how chromatin regulates gene expression is enhanced, improvements in the treatment of cancer can be made.

摘要

由于染色质的结构和组织对表观遗传学领域具有重要意义,它们最近备受关注。DNA甲基化以及发生在组蛋白上的翻译后修饰能够决定转录活性。在癌症发展过程中,肿瘤抑制基因会因DNA高甲基化而沉默,染色质修饰因子也不再以其通常的方式发挥作用。目前的表观遗传疗法能够利用这些表观突变的可逆性。在血液系统恶性肿瘤和一些实体瘤的治疗方面已经取得了进展。随着对染色质如何调节基因表达的认识不断加深,癌症治疗有望得到改善。

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本文引用的文献

1
Long-term epigenetic therapy with oral zebularine has minimal side effects and prevents intestinal tumors in mice.长期口服泽布替尼进行表观遗传治疗副作用极小,并可预防小鼠肠道肿瘤。
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A phase I biological study of MG98, an oligodeoxynucleotide antisense to DNA methyltransferase 1, in patients with high-risk myelodysplasia and acute myeloid leukemia.MG98(一种针对DNA甲基转移酶1的寡脱氧核苷酸反义药物)在高危骨髓增生异常综合征和急性髓系白血病患者中的I期生物学研究。
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Epigenetic interplay between histone modifications and DNA methylation in gene silencing.基因沉默中组蛋白修饰与DNA甲基化之间的表观遗传相互作用。
Mutat Res. 2008 Jul-Aug;659(1-2):40-8. doi: 10.1016/j.mrrev.2008.02.004. Epub 2008 Feb 29.
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Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation.真核生物基因组中单个核小体响应转录扰动的动态重塑。
PLoS Biol. 2008 Mar 18;6(3):e65. doi: 10.1371/journal.pbio.0060065.
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Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter.组蛋白去乙酰化酶抑制剂缩酚酸肽通过降低启动子上的CpG和H3K9甲基化来激活沉默基因。
Mol Cell Biol. 2008 May;28(10):3219-35. doi: 10.1128/MCB.01516-07. Epub 2008 Mar 10.
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Cell. 2008 Mar 7;132(5):887-98. doi: 10.1016/j.cell.2008.02.022.
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Urol Oncol. 2008 Mar-Apr;26(2):182-9. doi: 10.1016/j.urolonc.2007.01.020. Epub 2007 Nov 19.
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A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study.伏立诺他治疗持续性或复发性上皮性卵巢癌或原发性腹膜癌的II期研究:一项妇科肿瘤学组研究
Gynecol Oncol. 2008 May;109(2):182-6. doi: 10.1016/j.ygyno.2008.01.009. Epub 2008 Mar 4.