International journal of hematology-oncology and stem cell research最新文献

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The Role of HDACs as Leukemia Therapy Targets using HDI. HDAC作为使用HDI的白血病治疗靶点的作用。

International journal of hematology-oncology and stem cell research

Pub Date : 2015-10-01

Ahmad Ahmadzadeh, Elahe Khodadi, Mohammad Shahjahani, Jessika Bertacchini, Tina Vosoughi, Najmaldin Saki

Histone deacetylases (HDACs) are the enzymes causing deacetylation of histone and non-histone substrates. Histone deacetylase inhibitors (HDIs) are a family of drugs eliminating the effect of HDACs in malignant cells via inhibition of HDACs. Due to extensive effects upon gene expression through interference with fusion genes and transcription factors, HDACs cause proliferation and migration of malignant cells, inhibiting apoptosis in these cells via tumor suppressor genes. Over expression evaluation of HDACs in leukemias may be a new approach for diagnosis of leukemia, which can present new targets for leukemia therapy. HDIs inhibit HDACs, increase acetylation in histones, cause up- or down regulation in some genes and result in differentiation, cell cycle arrest and apoptosis induction in malignant cells via cytotoxic effects. Progress in identification of new HDIs capable of tracking several targets in the cell can result in novel achievements in treatment and increase survival in patients. In this review, we examine the role of HDACs as therapeutic targets in various types of leukemia as well as the role of HDIs in inhibition of HDACs for treatment of these malignancies.

组蛋白脱乙酰酶（HDAC）是引起组蛋白和非组蛋白底物脱乙酰的酶。组蛋白脱乙酰酶抑制剂（HDIs）是一类通过抑制HDAC来消除HDAC在恶性细胞中的作用的药物。由于HDAC通过干扰融合基因和转录因子对基因表达的广泛影响，HDAC引起恶性细胞的增殖和迁移，通过肿瘤抑制基因抑制这些细胞的凋亡。HDAC在白血病中的过表达评估可能是诊断白血病的一种新方法，为白血病治疗提供新的靶点。HDIs抑制HDAC，增加组蛋白的乙酰化，引起某些基因的上调或下调，并通过细胞毒性作用导致恶性细胞分化、细胞周期停滞和凋亡诱导。在识别能够追踪细胞中几个靶点的新HDI方面取得进展，可以在治疗和提高患者生存率方面取得新的成就。在这篇综述中，我们研究了HDAC作为各种类型白血病的治疗靶点的作用，以及HDIs在抑制HDAC治疗这些恶性肿瘤中的作用。

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引用次数: 0

Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy. 接受华法林治疗的伊朗患者CYP2C9和VKORC1多态性的鉴定。

International journal of hematology-oncology and stem cell research

Pub Date : 2015-10-01

Behzad Poopak, Saghar Rabieipoor, Nazila Safari, Emadedin Naraghi, Fatemeh Sheikhsofla, Gelareh Khosravipoor

Background: Although catalytic properties of different genetic polymorphisms of VKORC1 and CYP2C9 products have been identified, there is limited study available regarding warfarin dose requirement in Iranian patient population. This study investigates the impact of these polymorphisms on 115 patients, referred to Payvand Clinical and Specialty Laboratory for determining the appropriate dose of warfarin. RESULTS of the study may be applicable to individuals who are under warfarin therapy to avoid warfarin resistance or intolerance.

Subjects and methods: PT-INR test was utilized as a screening method. Genotyping were performed for VKORC1 and CYP2C9 using PCR method. Statistical analyses including unpaired t-test or ANOVA and regression were done using SPSS.

Results: VKORC1 GA was the most common genotype of VKORC1 allele among the study samples, with a rate of 57.4%. In CYP2C9 variant, 20% and 14.8% of subjects carried CYP2C9*1/*2 and CYP2C9*1/*3 genotyping, respectively. By contrast, the WT *1/*1 genotype was more abundant and dominant. The high frequency of VKORC1 (_1639) GA genotype (57.4%), was significant versus for the rest of the cohort (42.6%). In addition, a significant relationship was found between CYP2C9*1 and drug dose (P>0.021).

Conclusion: In this study, samples were characterized by higher frequencies of CYP2C9*1 and VKORC1 G/A, determined as higher warfarin taking doses. The results showed a significant relationship of the VCORC1 and CYP2C9 polymorphisms with warfarin sensitivity and severe side effects. Estimating right doses of warfarin to prescribe can help to reduce the risk of over- or under-anticoagulation and subsequently, the risk of thromboembolism or bleeding.

背景：尽管已经确定了VKORC1和CYP2C9产物的不同遗传多态性的催化特性，但关于伊朗患者群体中华法林剂量需求的研究有限。本研究调查了这些多态性对115名患者的影响，这些患者被送往Payvand临床和专业实验室，以确定华法林的适当剂量。研究结果可能适用于正在接受华法林治疗以避免华法林耐药性或不耐受的个体。受试者和方法：采用PT-INR试验作为筛选方法。使用PCR方法对VKORC1和CYP2C9进行基因分型。使用SPSS进行统计分析，包括非配对t检验或方差分析和回归分析。结果：VKORC1-GA是研究样本中最常见的VKORC1等位基因型，发生率为57.4%。在CYP2C9变体中，分别有20%和14.8%的受试者携带CYP2C9*1/*2和CYP2C9*1/*3基因分型。相反，WT*1/*1基因型更丰富且更具优势。VKORC1（_1639）GA基因型的高频率（57.4%）与队列中的其他基因型（42.6%）相比具有显著性。此外，CYP2C9*1与药物剂量之间存在显著关系（P>0.05）。结果显示，VCORC1和CYP2C9多态性与华法林敏感性和严重副作用之间存在显著关系。估计合适的华法林处方剂量有助于降低抗凝过度或不足的风险，以及随后血栓栓塞或出血的风险。

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