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MT1-MMP在肿瘤血管新生中的作用 总被引:1,自引:0,他引:1
基质金属蛋白酶 (MMPs)是包含至少 2 6个成员的酶家族。它们除降解细胞外基质外 ,还可以作用于其它的蛋白激酶、细胞趋化分子、生长因子、生长因子连接蛋白以及细胞表面分子等。MMPs的活性受组织型金属蛋白酶抑制物 (TIMPs)调控。MMPs和TIMPs在生理状态和癌症进程中的细胞外基质重塑过程中发挥重要作用 ,特别是MMP 2和TIMP 2。它们主要是调节肿瘤进展的早期阶段 ,如肿瘤生成和血管新生。 相似文献
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免疫球蛋白(Ig)是一组非常异质性的、具有统一结构模式的蛋白质分子,它们在有机体中担负着防止外来因子入侵的重要生物学作用。在脊椎动物进化过程中,形成了一种独特的遗传机制,产生大量具有不同活性中心的Ig分子(2·10~7)。了解这个组装机制的唯一方法是研究编码合成Ig的基因结构。近年来,这方面取得了很大的进展,一方面积累了关于Ig多肽链一级结构的资料; 相似文献
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雷学峰 《医学分子生物学杂志》1989,(3)
1988年度拉斯克(Lasker)基础医学奖授予两位分予生物学家——科罗拉多大学的Thornas Cech和麻省理工学院的Phfllip Sharp。Cech的主要贡献是发现多聚核糖核苷酸具有酶的作用。Sharp的工作则阐明了DNA分子中基因是如何被非编码顺序分隔以及这些非编码顺序又如阿在转录后被RNA剪切掉的。 相似文献
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近年来,随着癌症治疗手段的不断进步,虽然到 2017 年癌症死亡率总体下降 29%,但仍然是威胁全球人类生命健康的第二大疾病[1],癌症的治疗现状依然严峻.因晚期癌症患者放化疗及手术的局限性,分子靶向治疗逐渐成为国内外抗肿瘤研究的焦点,聚腺苷酸二磷酸核糖转移酶(poly(ADP-ribose) polymerase,P... 相似文献
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肿瘤基因治疗通过适当的载体在肿瘤细胞中表达抗癌基因以治疗癌症。目前肿瘤细胞中发现很多重要的致癌相关分子,它们有些与肿瘤细胞无限繁殖密切相关,有些能够抑制细胞的凋亡,有些能够促进肿瘤细胞血管新生或者逃避免疫监视。这些分子无疑是今后肿瘤基因治疗中的理想靶向分子。本文选取了目前肿瘤基因治疗研究中较新并具有一定代表性的2种致癌相关分子:缺氧诱导因子1(HIF-1)、信号转导与转录活化因子3/5(STAT3/5),对其特点及其在癌症治疗中的应用作一综述。 相似文献
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人的红细胞不能合成嘌呤,但可通过摄入现成的嘌呤硷(如次黄嘌呤、鸟嘌呤和腺嘌呤)以满足它们合成嘌呤核苷酸的需要。在放射性嘌呤硷掺入红细胞的研究中,嘌呤硷在生理浓度时,细胞内几乎没有测出标记的自由硷。仅仅观察到加入硷的单核苷酸、二核苷酸和三核苷酸。两种嘌呤磷酸核糖转移酶(嘌呤-PRTs)是使嘌呤硷进入细胞的酶。在磷酸核糖焦磷酸(PRPP)存在时,次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HG-PRT)催化次黄嘌呤和鸟嘌呤分别转变为IMP和GMP。在PRPP存在时腺嘌呤磷酸核糖转移酶(A-PRT)催化腺嘌呤转变为AMP。现已证明,嘌呤硷可借助中间载体转移到哺乳动物的细胞中。 相似文献
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穿孔素 (Perforin)是存在于CTL、NK细胞杀伤颗粒中的细胞毒性蛋白 ,在保护机体抗胞内病原体如细菌、病毒、寄生虫感染、抗肿瘤和同种排斥应答中起重要作用 ,是免疫系统重要的效应分子。近年来随着FHL病因的阐明 ,逐渐发现穿孔素也是一种重要的免疫调节分子。本文综述了穿孔素在病毒感染、肿瘤免疫、自身免疫病及GVHD中的调节作用 ,以及穿孔素免疫调节的作用机制。 相似文献
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穿孔素(Perforin)是存在于CTL、NK细胞杀伤颗粒中的细胞毒性蛋白,在保护机体抗胞内病原体如细菌、病毒、寄生虫感染、抗肿瘤和同种排斥应答中起重要作用,是免疫系统重要的效应分子。近年来随着FHL病因的阐明,逐渐发现穿孔素也是一种重要的免疫调节分子。本文综述了穿孔素在病毒感染、肿瘤免疫、自身免疫病及GVHD中的调节作用,以及穿孔素免疫调节的作用机制。 相似文献
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MicroRNAs (miRNAs)是一类长约22 nt的非编码单链RNA分子,在转录后水平调控基因的表达.miRNA能特异性诱导靶基因mRNA降解及抑制靶基因mRNA的翻译,同时在细胞的发生、发展、增殖、分化和凋亡过程中发挥重要的调节作用[1].目前,人类基因组中已确认的miRNAs约500个,其中超过200种miRNAs与癌症发生有关.近年来,miRNA已被证实在癌症的发生、发展中发挥着重要的调控作用.本文就miRNA与癌症的相关性作一综述. 相似文献
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MicroRNA与脑发育及神经系统疾病 总被引:3,自引:0,他引:3
MicroRNA是一类非编码的小RNA,它提供基因的转录后调控。近年来,MicroRNA成为了研究热点。在脑组织中miRNAs较丰富,它在脑组织的发育和分化过程中起关键作用;miRNAs表达随着胚胎脑组织的发育而变化。在细胞分化过程中,miRNAs起到建立并维持细胞固有特征的作用。同时miRNAs还参与神经功能的实施,如突触可塑性。miRNAs通过调控突触处的mRNA的翻译来维持突触可塑性。它们的异常表达还与一些神经系统疾病有关,如胶质母细胞瘤,Tourette综合征等。 相似文献
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miRNA是近年来发现的一种内源性短序列非编码单链RNA,成熟的miRNA通过两种依赖于序列互补性的机制引起靶mRNA的降解或者抑制其翻译,在基因表达调控中扮演重要的角色。miRNA与内分泌代谢病关系密切,有潜在的生物治疗价值。 相似文献
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涡虫由于其体内存在丰富的成体干细胞——新母细胞(neoblasts)而具有极强的再生能力。目前,涡虫已成为再生生物学研究的重要模式动物,neoblasts也成为生物医学领域的重要工具细胞。但关于调控涡虫再生和neoblasts增殖的基因网络仍不十分清楚。微小RNAs(miRNAs)是广泛存在于真核生物中的一类内源性、小片段、非编码RNA,可通过特异性识别并结合目的RNA,负调控功能基因的表达。近期的研究提示,miRNAs可能参与涡虫再生的调控。我们就miRNAs调控涡虫再生及neoblasts,增殖和分化特性的新近研究成果及进展进行综述。 相似文献
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Recent molecular analyses have contributed to our knowledge about the chromogranin/secretogranin (Cg/Sg) family and their utility in diagnostic pathology. The genes for five of these proteins have been cloned, and the deduced amino acid sequences have provided insights into the structure and possible functions of the Cgs/Sgs, including their role as prohormones. Northern hybridization and in situ hybridization histochemistry have provided a great deal of information about the tissue distribution of the Cg/Sg gene products. Some neoplasms such as small cell lung carcinomas, which have little stored Cg/Sg protein, have abundant cytoplasmic mRNAs that can be readily detected by hybridization studies. Some other neoplasms such as neuroblastomas have decreased CgA and increased SgII mRNAs during maturation to ganglioneuromas. There is also a differential expression of Cgs/Sgs in some endocrine neoplasms such as parathyroid adenomas, which express abundant CgA mRNA and little CgB mRNA, and in pituitary prolactinomas, which express CgB mRNA but not CgA mRNA. The mRNA for CgA has been found unexpectedly in some neoplasms such as 15% of colonic adenocarcinomas. Thus, molecular approaches in the analysis of Cgs/Sgs should contribute to the diagnosis of endocrine neoplasms and may provide support for a molecular classification of neoplasms in diagnostic pathology. 相似文献
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MicroRNAs (MiRNAs) are small noncoding RNAs that function as regulators of gene expression to control cell growth and differentiation. In this study, we analyzed miRNA and mRNA expression in the livers of rats treated with a carcinogenic dose of comfrey (Symphytum officinale) for 12 weeks. Groups of six rats were fed a normal diet or a diet containing 8% comfrey root. The animals were sacrificed 1 day after the last treatment and the livers were isolated for miRNA expression analysis using LC Sciences miRNA microarrays and for mRNA expression analysis using Affymetrix rat genome microarrays. MiRNA expression levels were significantly changed by comfrey treatment. The treated samples were separated clearly from the control samples in both principal component analysis (PCA) and hierarchical clustering analysis (HCA). Quantitative measurements of seven miRNAs using TaqMan real-time PCR were consistent with the microarray results in terms of fold-change and the direction of the change in expression. Forty-five miRNAs (P < 0.01) and 1,921 mRNAs (q = 0) were significantly changed by comfrey treatment. Using a target prediction algorithm, 434 differentially expressed genes (DEGs) were predicted to be targeted by the differentially expressed miRNAs (DEMs). The DEM-targeted DEGs were more likely to be involved in carcinogenesis than the DEGs that were not targeted by the DEMs. The nontargeted DEGs were enriched in noncancer-related biological processes. Our data suggest that comfrey may exert its carcinogenic effects by disturbing miRNA expression resulting in altered mRNA levels of the DEM-targeted genes that are functionally associated with carcinogenesis. 相似文献
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Estrogens have been known to induce PRL cell hyperplasia in the anterior pituitary of some species for many decades. Recent studies have shown variable susceptibility to estrogen-induced hyperplasia in different strains of rats. The distinction between hyperplastic pituitaries and adenomas is usually not made by most investigators in this field, although true neoplasms can usually be propagated by serial transplantation. The growth of transplantable tumors is usually inhibited by estrogen in vivo. Estrogens have a biphasic effect on pituitary cell proliferation in vitro with higher concentrations of estradiol inhibit cell growth, and lower concentrations stimulating PRL secretion. Estrogens can regulate PRL gene methylation in vivo thus affecting PRL mRNA expression. Recent studies have suggested that estrogen regulates signal transduction by stimulating protein kinase C. Estrogens also regulate specific proto-oncogenes such as c-myc and c-fos. These observations may help to explain some of the regulatory effects of estrogens on cell proliferation and tumor development. 相似文献
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Vivien Wang Dr Wei Wu 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2009,23(1):15-23
MicroRNAs (miRNAs) are non-protein-coding small RNA molecules that negatively regulate target messenger RNA through degradation or suppression of protein translation. MiRNAs play important roles in the control of many biologic processes, such as development, differentiation, proliferation, and apoptosis. Increasing evidence shows that aberrant miRNA expression profiles and unique miRNA signaling pathways are present in a variety of cancers. MiRNAs function as oncogenes or tumor suppressors during tumor development and progression. Experimental evidence demonstrates that correction of specific miRNA alterations using miRNA mimics or antagomirs can normalize the gene regulatory network and signaling pathways, and reverse the phenotype in cancerous cells. MiRNA-based gene therapy provides an attractive anti-tumor approach for integrated cancer therapy. In this review, we focus on miRNA-based treatment for cancers, summarize the delivery systems used in experimental and preclinical research, such as liposomes, viral vectors, and nanoparticles, and consider the safety and toxicity of miRNA therapy. 相似文献
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Bora Kim Jae-ho Lee Jong Wook Park Taeg Kyu Kwon Seong Kyu Baek Ilseon Hwang Shin Kim 《Clinical and experimental medicine》2014,14(3):331-336
MicroRNAs (miRNAs) regulate gene expression through degradation and/or translational repression of target mRNAs. Dysregulations in the miRNA machinery may be involved in carcinogenesis of colorectal cancer (CRC). The purpose of the current study was to evaluate the DiGeorge syndrome critical region gene 8 (DGCR8) and argonaute 2 (AGO2) mRNA expression in CRC and to evaluate the value of clinical parameters on their expression. We investigated the mRNA expressions of DGCR8 and AGO2 in 60 CRC tissues and adjacent histologically non-neoplastic tissues by using quantitative real-time PCR. Our study revealed that the mRNA expression level of DGCR8 is up-regulated in CRC. However, AGO2 mRNA expression was not significantly altered in CRC tissues. Neither DGCR8 nor AGO2 mRNA expression level was not associated with any clinical parameters, including age, tumor stage, CEA titer, and BMI in CRC cases. However, the mRNA expression levels of DGCR8 and AGO2 were positively correlated to each other. This study demonstrated for the first time that the DGCR8 mRNA expression level was up-regulated in CRC, suggesting its important role in pathobiology of colorectal carcinogenesis. 相似文献
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