AT丰富结合域1A基因在消化系统肿瘤中的研究进展

<正>2010年,Wiegand等[1]对42例卵巢透明细胞腺癌患者的研究发现AT丰富结合域1A(ARID1A)基因约有57%出现突变的报道后,很多学者在乳腺癌[2]、子宫内膜癌[3]、胃癌[4]和大肠癌[5]中发现ARID1A基因的异常表达和突变。本文就ARID1A基因与多种消化系统肿瘤的关系做一综述。1 ARID1A的结构和功能     

OATPs家族在肿瘤中的表达及肿瘤治疗中的作用

药物转运体OATPs在一些肿瘤药物体内吸收、分布与排泄过程中有重要的作用,同时近年来较多的研究关注了OATPs在各类型肿瘤细胞及肿瘤组织中的表达,以及OATPs的表达对肿瘤的发生发展、治疗和诊断的影响,OATPs可能成为新的肿瘤治疗靶点。该文综述了OATPs家族在肿瘤中的表达及它们对肿瘤治疗的潜在作用和临床意义。     

基于Oncomine和TCGA数据库分析SLC2A1基因在肺腺癌中的表达意义

目的阐明SLC2A1基因在肺腺癌中的表达及临床意义。方法通过检索Oncomine和TCGA等生物信息数据库中有关SLC2A1的信息,并对所获取的数据资料挖掘并进行二次分析,对SLC2A1在肺腺癌中的作用进行荟萃分析。结果 Oncomine数据库中共收集了448项不同类型SLC2A1的研究结果,关于在肿瘤与对照组织中SLC2A1表达有统计学差异的结果有47项,其中SLC2A1表达增高的有43项,表达降低的有4项。肺腺癌中高表达的研究有8项、低表达的有0项。共有8项研究数据集涉及SLC2A1在肺腺癌组织和正常组织中的表达,包括786例样本。在数据库中综合比较这8项研究成果,发现与对照组相比,SLC2A1在肺腺癌中的表达高于正常组织(P0.05)。另外,免疫组织化学显示SLC2A1在肺腺癌组织中表达较强或中等,而在正常组织中表达较弱或呈阴性。TCGA数据库中挖掘的结果也同样显示高表达SLC2A1的患者总体死亡率较高,低表达SLC2A1的患者预后较好(P0.05)。结论基于公共数据库中肿瘤相关的基因信息,提示SLC2A1的m RNA水平在肺腺癌组织中呈现高表达,并与肺腺癌预后相关,其有望成为肺腺癌药物治疗的重要治疗靶点。     

CYP27A1在肿瘤进程中的作用研究进展

CYP27A1是细胞色素P450 27亚族的成员之一,存在于多种组织的线粒体内,其主要功能是通过经典通路和酸性通路催化胆汁酸合成过程中的羟化、维持体内胆汁酸的平衡,催化维生素D3的生物活化.CYP27A1与多种肿瘤的形成密切相关,如乳腺癌、前列腺癌、结肠直肠癌以及肝癌等,本文总结了CYP27A1在3种常见肿瘤中的作用,以期为肿瘤发生机制研究奠定基础.     

TL-1A和IL-17在类风湿关节炎中的作用及其临床意义

肿瘤坏死因子样配体1A（TL-1A）和白细胞介素17（IL-17）与类风湿关节炎（RA）发病和病情进展密切相关,还可能与生物制剂治疗RA的疗效差异有关。本文就TL1A和IL-17在RA发病机制中的作用及其临床意义的相关研究作一综述。     

长链脂酰辅酶A合成酶在肿瘤中的研究进展

长链脂酰辅酶A合成酶(ACSL)包括5种不同亚型,是催化脂肪酸活化的关键酶,在脂肪酸代谢中发挥重要作用。ACSL在许多类型的肿瘤中异常表达,在促进肿瘤细胞增殖或凋亡以及影响肿瘤进程方面具有复杂的功能。ACSL通过不同的信号传导途径和分子机制调节肿瘤进展,其异常表达对肿瘤组织的分化,肿瘤的预后和复发均有一定的影响,有望成为新的标志物及治疗靶点。了解ACSL在肿瘤中的确切作用以及所涉及的分子机制,可为寻找肿瘤诊治新靶标、开发基因治疗新策略提供思路。本文对ACSL与肿瘤的相关研究作一综述。     

肿瘤干细胞的研究进展

随着对肿瘤研究的不断深入,以及对干细胞了解的日益加深,越来越多的证据提示肿瘤中某些细胞具有干细胞特性,并提出了肿瘤干细胞的学说,认为肿瘤的生长、转移以及耐药等均于肿瘤干细胞的关系密切.该文综述了肿瘤干细胞的发现、特点,以及在肿瘤的诊断、治疗和预后判断中的作用.     

多梳基因-1在肠癌组织中的表达及其临床意义

目的检测多梳基因家族Bmi-1蛋白在大肠癌组织中的表达,探讨其相关的临床意义。方法收集来笔者所在医院进行治疗的大肠癌患者32例,按照Dukes分期分为A、B、C、D四期,另取正常组织作为对照组;利用免疫组化方法检测大肠癌组织中Bmi-1蛋白的表达。结果 Bmi-1蛋白在大肠癌组织中的表达率为56.3%,显著高于正常对照组织中的15.0%(P<0.01)。Bmi-1蛋白在大肠癌组织中的表达与肿瘤的Dukes临床分期相关(P<0.01),与患者的性别和年龄无关(P>0.05)。结论 Bmi-1蛋白在大肠癌的发生发展中起到一定的作用,可以用于肿瘤的良恶性鉴别诊断、临床分级以及判断预后等方面,具有显著的临床意义。     

Ras相关区域家族1A基因在宫颈癌组织中的表达及其甲基化调控研究

目的探讨Ras相关区域家族(RASSF)1A基因在宫颈癌中的作用。方法采用实时荧光定量聚合酶链反应(RT-PCR)技术检测宫颈癌中RASSF1A基因的表达状况;采用甲基化特异PCR技术检测RASSF1A启动子区5c-CpG岛的甲基化状态;通过细胞增殖和侵袭实验检测RASSF1A在宫颈癌细胞中的功能。结果本研究检测了65例宫颈癌和20份正常宫颈组织样本中RASSF1A的表达水平,结果显示其在宫颈癌中的表达水平明显低于正常宫颈组织,且差异有统计学意义。RASSF1A的表达与患者的年龄、淋巴结转移、肿瘤大小及病理类型无关,而与肿瘤的TNM分期有关。宫颈癌组织中RASSF1A启动子区5c-CpG岛的甲基化水平明显高于正常宫颈组织。RASSF1A可以抑制宫颈癌细胞的增殖和侵袭。结论 RASSF1A基因启动子区5c-CpG岛的高甲基化可能是参与宫颈细胞癌变的重要机制之一。     

高通量DNA测序技术在抗体新药研发中的应用

自2005年首次报道了一种基于微乳液PCR技术的高通量DNA测序技术 (high-throughput DNA sequencing technology) 以来, 高通量DNA测序平台已经发展为基因组和各种基因文库序列检测的强大工具。大容量的抗体基因库是目前获得抗体新药的基础, 高通量DNA测序技术为从海量的抗体基因库中快速发现功能抗体分子提供了可能。本文就近几年高通量DNA测序技术在抗体基因库的多样性分析, 抗体CDR3区的高通量测序、频率分析、功能基因发现及各种展示技术与高通量DNA测序技术的对接应用等方面进行了综述, 以期为抗体新药的研发提供一条新的技术路线。     

Low-LET-induced radioprotective mechanisms within a stochastic two-stage cancer model

A stochastic two-stage cancer model with clonal expansion was used to investigate the potential impact on human lung cancer incidence of some aspects of the hormesis mechanisms suggested by Feinendegen (Health Phys. 52 663-669, 1987). The model was applied to low doses of low-LET radiation delivered at low dose rates. Non-linear responses arise in the model because radiologically induced adaptations in radical scavenging and DNA repair may reduce the biological consequences of DNA damage formed by endogenous processes and ionizing radiation. Sensitivity studies were conducted to identify critical model inputs and to help define the changes in cellular defense mechanisms necessary to produce a lifetime probability for lung cancer that deviates from a linear no-threshold (LNT) type of response. Our studies suggest that lung cancer risk predictions may be very sensitive to the induction of DNA damage by endogenous processes. For doses comparable to background radiation levels, endogenous DNA damage may account for as much as 50 to 80% of the predicted lung cancers. For an additional lifetime dose of 1 Gy from low-LET radiation, endogenous processes may still account for as much as 20% of the predicted cancers (Fig. 2). When both repair and scavengers are considered as inducible, radiation must enhance DNA repair and radical scavenging in excess of 30 to 40% of the baseline values to produce lifetime probabilities for lung cancer outside the range expected for endogenous processes and background radiation.     

Colony and phage-plaque direct sequencings by dye-terminator methods

Direct sequencing using lambda phage DNA and E. coli colonies with plasmid DNA is a very powerful technique. Almost all of the reported direct sequencing methods involve either radioactive sequencing or fluorescent dye-primer sequencing. We present a direct colony sequencing strategy that uses a dye terminator (BigDye terminator kit) together with dye primer sequencing. We found that single-colony sequencing with the terminator yielded about 500 base pairs of sequence information. Signal strength was not improved when the number of cycles increased to 40. The colony used for the sequencing was estimated to contain about 5.6 x 10(7) cells. In addition, although a single plaque consisted of 2 x 10(6) cells, the pfu was not high enough to read with single-cycle sequencing, and only about 300 base pairs of sequence information were obtained from a single plaque using two cycle-sequencing reactions (re-cycle sequencing). The optimal amounts of the template were 500 ng of purified lambda DNA and 1 x 10(7) pfu of the lambda phage suspension, but with BigDye terminator it was possible to detect as little as 50 ng of purified lambda DNA and 2 x 10(6) pfu for lambda phage suspensions. Thus, colony direct sequencing and plaque direct sequencing are estimated to be very useful for rapid and high-throughout screening of genomic and cDNA libraries.     

新的良性家族性婴儿惊厥位点候选基因的突变分析

目的 前期工作中我们将一中国良性家族性婴儿惊厥(BFIC)家系的致病基因定位于1p36.12～1p35.1上,为了进一步克隆该致病基因,对该定位区间内的候选基因进行突变分析.方法 通过生物信息学查询,选择SLC9A1、STMN为候选基因,应用Primer 3引物设计、PCR 扩增和直接测序的方法 进行候选基因的突变检测...     

The use of automated sequencing techniques to investigate the sequence selectivity of DNA-damaging agents

In this review, the use of automated DNA sequencing techniques to determine the sequence specificity of compounds that interact with DNA is discussed. The sequence specificity of a DNA-damaging agent is an essential element in determining the cellular mechanism of action of a drug. A number of DNA-damaging compounds are mutagenic, carcinogenic, as well as being widely used as cancer chemotherapeutic agents. The distribution of lesions in a sequence of DNA can give vital clues in the determination of the precise mechanism of interaction of the agent with DNA. The DNA sequence specificity of a number of DNA-damaging agents has been delineated using automated DNA sequencing technology, and these studies are discussed in this review. The current state-of-the-art methodology involves capillary electrophoresis with laser-induced fluorescence detection usually on an Applied Biosystems ABI 3730 capillary sequencer. This current technique has higher resolution, greater sensitivity, higher precision, more rapid separation times, is safer and easier to perform than previous methods. The two main methods to determine the DNA sequence selectivity of compounds that interact with DNA are described: end labelling and the polymerase stop assay. The interaction of the antitumour drug, bleomycin, with DNA is utilized to illustrate the recent technological advances.     

Targeting the DNA repair defect of BRCA tumours

Carriers of heterozygous mutations in BRCA1 or BRCA2 are strongly predisposed to breast and ovarian cancers. Cancers arising in these individuals have consistently lost the wild-type allele during tumour progression, and are therefore deficient in BRCA1 or BRCA2 function. Both BRCA1 and BRCA2 proteins have been implicated in the repair of double-strand DNA breaks by homologous recombination. This functional role in DNA repair could be exploited in the treatment of BRCA-deficient cancers by targeting the tumours with drugs that create DNA damage highly reliant on BRCA1 or BRCA2 for repair.     

Simultaneous determination of single nucleotide polymorphisms of MDR1 genes by electrochemical DNA chip

The on-chip genotyping system ("the electrochemical DNA chip") has been developed as a more cost-effective genotyping system and was applied to MDR1 genotyping in the present study, which is required for wide use in clinical application and for personalized medication based on genotype. The electrochemical DNA chip was optimized and applied to simultaneous genotyping of four MDR1 polymorphisms (T-129C, C1236T, G2677(A,T) and C3435T) using synthetic model oligonucleotide DNA and human genomic DNA. The electrochemical DNA chip successfully gave the T-129C, C1236T, G2677(A,T) and C3435T genotypes, which were completely consistent with those determined by direct sequencing. In conclusion, the electrochemical DNA chip is useful for simultaneous determination of some genotypes and haplotypes, and efficient genotyping using this system can support future genotype-phenotype studies at a large scale.