共查询到19条相似文献,搜索用时 138 毫秒
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从临床和DNA甲基化两方面报告含砷中药治疗骨髓增生异常综合征(MDS)研究进展.共经治患者千余例,总有效率80%左右;已有患者停止治疗1年以上,外周血象指标仍然全部正常;MDS的异常甲基化不仅表现为明显高甲基化,也表现为一些基因的低甲基化.疗效机制研究表明含砷中药治疗MDS对异常甲基化有双向调节作用,含砷中药治疗的主要作用机制是去甲基化,也可使部分低甲基化基因高甲基化. 相似文献
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表观遗传改变与基因改变有一个重要的区别就是表观遗传改变是可逆的,通过使用相应的表观遗传药物可使沉默的抑癌基因重新表达。骨髓增生异常综合征(MDS)的表观遗传治疗已经取得了很大的发展,当前应用于临床的表观遗传药物主要包括DNA去甲基化药物和去乙酰化酶抑制剂。得到FDA批准上市的DNA去甲基化药物5-氮杂胞苷和地西他滨均为MDS治疗药物,可作为中高危患者尤其是不能耐受化疗的老年患者重要的治疗选择;去乙酰化酶抑制剂如丙戊酸等目前在治疗MDS中大多处于I期临床试验阶段,可能在治疗低危MDS中有一定价值,但其剂量和治疗效果尚需进一步评估;去甲基化药物和去乙酰化抑制剂二者联用治疗MDS可能具有协同作用,但目前的临床试验尚不能证实其优于去甲基化药物的单用,仍需大样本的临床病例和合理的治疗方案来验证其安全有效性。 相似文献
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表观遗传学异常是骨髓增生异常综合征(myelodysplastic syndromes,MDS )发病的重要机制之一,DNA 甲基化异常是MDS 最常见的表观遗传学改变。抑制DNA 异常甲基化可以改善部分MDS 患者的病情,延长其生存期。目前被批准用于MDS 临床治疗的去甲基化药物主要有阿扎胞苷和地西他滨,这两种药物在MDS 患者中均显示出一定的疗效。本文对该药的应用及进展研究进行综述。 相似文献
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骨髓增生异常综合征(myelodysplastic syndrome,MDS)的发病机制涉及多阶段、多因素,基因改变与表观遗传修饰可能共同参与了这一过程.DNA甲基化是表观遗传学中一种最为重要的修饰,MDS患者常表现为总体DNA高甲基化.使用DNA甲基转移酶(DNA methyltransferase,DNMT)抑制剂降低总体甲基化水平,在MDS患者中取得了富有成效的临床反应及血液学改善.DNMT抑制剂可分为两类:5-氮杂胞苷(5-azacytidine,5-Aza-CdR)、地西他滨(5-Aza-2-deoxycytidine,decitabine)等核苷和核苷衍生物类抑制剂,它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善,但缓解率、疗效尚不够令人满意;肼苯哒嗪等非核苷类抑制剂.非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功,为MDS去甲基化治疗药物的研究开启了一种新思路. 相似文献
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食管鳞癌DNA甲基化的研究进展 总被引:1,自引:0,他引:1
近年来研究结果表明,相关抑癌基因启动子区超甲基化导致的基因表达紊乱已成为食管癌发病机制研究的热点之一.众多研究表明DNA甲基化在食管癌的发生、侵袭和转移过程中发挥了积极的作用,外周血DNA甲基化谱可作为食管癌早期诊断、预后判断及随访的检测指标,有望将抑癌基因去甲基化作为食管癌的治疗靶点. 相似文献
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自1983年Feinberg等发现在肿瘤细胞中存在着基因总体低甲基化和局部高甲基化的现象后,国内外围绕DNA甲基化问题进行了大量的研究,并取得了很大的进展。越来越多的证据表明,DNA甲基化异常状态尤其是抑癌基因的高甲基化表达在白血病的发生发展、诊断治疗及预后评估等方面发挥了重要的作用。现作者就近年来DNA异常甲基化与白血病的关系及去甲基化药物地西他滨在治疗白血病中的应用作一综述。 相似文献
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【摘要】 骨髓增生异常综合征(MDS)是一组起源于造血干/祖细胞的获得性、克隆性、异质性疾患。中国与西方国家MDS患者具有不同的遗传学特征。以砷剂青黄散为主治疗MDS已取得肯定临床疗效。疗效机制研究表明含砷中药治疗不能改变MDS患者已有的染色体异常,但MDS患者异常增高的甲基化显著减低,含砷中药治疗的主要作用机制是去甲基化。血砷浓度测定表明有效血砷质量浓度为(19.39±10.36)μg/L,明显低于砷剂治疗急性早幼粒细胞白血病所需血砷浓度。进一步研究砷剂的去甲基化机制、进行个体化血砷浓度检测和疗效关系的研究是今后研究的方向。 相似文献
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DNA甲基化与食管癌的关系 总被引:2,自引:0,他引:2
肿瘤细胞普遍存在DNA甲基化模式的改变,DNA甲基化异常包括原癌基因低甲基化和抑癌基因高甲基化。近年来研究结果表明,在食管癌发生过程中同样存在相关抑癌基因启动子区甲基化导致的基因表达的紊乱。其中由DNA甲基转移酶(DNA methyltransferase,DNMT)和去甲基化酶的活性改变导致的抑癌基因CpG岛超甲基化的研究,已成为食管癌发病机制研究中的热点之一。综述DNA甲基化的特点及其抑制基因转录和表达的分子生物学机制;DNA异常甲基化与食管癌发生发展的关系;食管癌相关肿瘤抑制基因的甲基化谱构成了食管癌独特的表遗传学标志;目前常用的甲基化检测手段及各方法的优缺点;DNA甲基化和去甲基化研究的展望及所需要解决的的问题等。 相似文献
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Andreas D. ?rskov Marianne B. Treppendahl Anni Skovbo Mette S. Holm Lone S. Friis Marianne Hokland Kirsten Gr?nb?k 《Oncotarget》2015,6(11):9612-9626
The hypomethylating agents (HMAs) are standard therapy for patients with higher-risk myelodysplastic syndrome (MDS); however, the majority of the patients will lose their response to HMAs over time due to unknown mechanisms. It has recently been shown that T cell expression of the immunoinhibitory receptor PD-1 is regulated by DNA methylation. In 12 of 27 patients (44%) PD-1 promoter demethylation was observed in sorted peripheral blood T cells isolated over consecutive cycles of treatment with 5-azacytidine (5-aza). The PD-1 promoter demethylation correlated with an increase in PD-1 expression. Moreover, demethylation of the PD-1 promoter correlated with a significantly worse overall response rate (8% vs. 60%, p = 0.014), and a trend towards a shorter overall survival (p = 0.11) was observed. A significantly higher baseline methylation level of the PD-1 promoter was observed in T cells of non-responding patients compared to healthy controls (p = 0.023).Accordingly, in addition to their beneficial function, HMAs induce PD-1 expression on T cells in the MDS microenvironment, thereby likely hampering the immune response against the MDS blasts. Thus, we suggest that activation of the PD-1 checkpoint during HMA treatment can be a possible resistance mechanism, which may be overcome by combination therapy with a PD-1 pathway inhibitor. 相似文献
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Characterization of DNA demethylation effects induced by 5-Aza-2'-deoxycytidine in patients with myelodysplastic syndrome 总被引:2,自引:0,他引:2
Azanucleoside drugs such as 5-azacytidine (Vidaza) and 5-aza-2'-deoxycytidine (decitabine, Dacogen) function as DNA methyltransferase inhibitors in vitro and represent promising new drugs for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia. In this study, we aimed to determine the effect of decitabine on the genomic methylation level in MDS patients. Comparison of different assays established micellar electrokinetic chromatography as a reliable method for the analysis of genomic methylation levels. When used for the determination of DNA methylation levels in bone marrow DNA from MDS patients during various time points of decitabine treatment, the results revealed a significant (up to 70%) demethylation in five of seven patients. Interestingly, genome-wide demethylation appeared after karyotype normalization, which suggests demethylation of nonclonal cells. Drug-induced demethylation dynamics were also confirmed by bisulfite sequencing of pericentromeric satellite elements. Our results are the first to show a genome-wide demethylating activity of decitabine in tumor material. In addition, our data uncovers novel targets of decitabine-mediated demethylation that are important for the refinement of treatment schedules with demethylating drugs. 相似文献
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目的:了解DNMT3A基因突变在骨髓增生异常综合征(MDS)患者中的发生率、分布情况及临床意义。方法:选取2012年 4月至2018年6月在湘雅二医院和湘潭市中心医院住院的85例MDS患者为研究对象。提取患者外周血基因组DNA,针对DNMT3A基因突变热点R882位点设计合成引物,采用聚合酶链式反应法扩增DNMT3A基因23号外显子整个编码区基因片段,再将扩增产物纯化后测序,分析DNMT3A基因突变在本组患者中的发生率、分布情况及临床意义。结果:85例MDS患者中检测到5例DNMT3A基因突变,突变阳性率5.9%,其中R882H和R882C基因突变各2例,R882P基因突变1例,未见R882S基因突变。常规化疗联合去甲基化药物地西他滨治疗后,1例患者一度获得血液学完全缓解,复杂染色体核型恢复正常,但是1月后转为急性白血病并发严重感染死亡,1例治疗后稳定,2例治疗后疾病进展,1例死于肺部感染。结论:MDS中DNMT3A基因突变率低,其突变多预示预后较差,并可能更快地向急性髓性白血病转化,选择去甲基化药物治疗可能获益。 相似文献
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目的:探讨骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者免疫表型特点及预后,以及流式细胞术积分系统(flow cytometric scoring system,FCSS)在MDS中的应用.方法:回顾性分析2006年至2012年根据FAB及WHO标准诊断为MDS的1 12例患者.采用多参数流式细胞术(multiparameter flow cytometry,MFC)研究其免疫表型改变,分别对幼稚细胞群、成熟粒细胞群、单核细胞群及有核红细胞进行分析,并对这些患者进行随访及生存期分析.结果:幼稚细胞群异常表达CD7占20.54%,成熟粒细胞群CD13/CD16结构关系异常占57.14%,单核细胞群CD56异常表达占21.43%,根据FCSS进行分组,各分组之间中位总生存期(mOS)存在显著差异,并且随着FCSS积分的增加,生存期显著缩短.结论:免疫表型异常对MDS的诊断及预后评估有重要意义,FCSS标准作为一种量化的流式细胞术积分系统,可以对MDS的诊断及预后评估起重要作用. 相似文献
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Hyun Ae Jung Chi Hoon Maeng Moonjin Kim Sungmin Kim Chul Won Jung Jun Ho Jang 《Oncotarget》2015,6(18):16653-16662
Despite the efficacy of decitabine to myelodysplastic syndrome (MDS), there is a wide range of responses, and no definite predictive marker has been identified. This study aimed to describe the efficacy of decitabine and to identify potential predictors of response and survival in patients with MDS. We retrospectively analyzed clinical data of MDS patients at Samsung Medical Center between August 2008 and August 2011. The response assessment was conducted using the International Working Group (IWG) response criteria for MDS. We analyzed 101 MDS patients (total 613 cycles) who received decitabine for a median of four cycles. The overall response was 52.5% (n = 53/101). The median time to any response was two cycles with the median overall survival of 16.7 months. Patients who showed hematologic improvement had significantly longer survival than those who did not (9.8 vs. 22.9 months, p = 0.004). The difference in OS was evident in the Intermediate-2/High risk group (p = 0.002) but not in the Intermediate-1 risk group (p = 0.145). Multivariate analysis confirmed that platelet response (no platelet transfusions for at least 3 days) during the second cycle of treatment was an independent predictor for response, OS and Leukemia free survival. Based on the results of this study, for patients with hematological improvement, recovery of platelet count by the second cycle of therapy can be used as an early predictive marker of improved survival and an increased response rate. 相似文献